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Clin Res Cardiol ; 109(5): 539-548, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31401672


AIMS: In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6 months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6 months. METHODS AND RESULTS: In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9 days after PCI (before placebo/BMC treatment) and after 6 months. Infarct perfusion improved from baseline to 6 months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect-infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect-upslope ratio (0.54 ± 0.23 to 0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect-upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6 months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67-0.92). CONCLUSION: Infarct perfusion improves from baseline to 6 months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial.

Eur Heart J ; 38(39): 2936-2943, 2017 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-28431003


Aims: Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway. Methods and results: Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events. Conclusion: The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy.

Transplante de Medula Óssea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Células da Medula Óssea/efeitos da radiação , Método Duplo-Cego , Feminino , Raios gama , Humanos , Infusões Intralesionais , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Transplante de Células-Tronco/métodos , Células-Tronco/efeitos da radiação , Transplante Autólogo , Resultado do Tratamento , Função Ventricular Esquerda/fisiologia
Clin Genitourin Cancer ; 15(2): 280-290.e3, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27863831


INTRODUCTION: Treatment-related hypertension (tHTN) is frequent during sunitinib treatment. However, data on risk factors and treatment of tHTN remain scarce. PATIENTS AND METHODS: Patients with metastatic renal-cell carcinoma treated with sunitinib from June 2004 to December 2011 were included. Medical records were retrospectively analyzed for tHTN risk factors and antihypertensive treatments (AHT). Descriptive statistics, Cox regression, and competitive risk models were applied. RESULTS: A total of 51 (70.8%) of 72 patients developed tHTN after a median sunitinib treatment of 28 days. Mean blood pressure increased from 130/75 (range, 90 to 190/58 to 101) mm Hg on day 1 to 140/80 (range, 90 to 190/60 to 120, P < .001) mm Hg on day 28. Standard dose of sunitinib, age > 50 years, and prehypertension were identified as independent risk factors for tHTN. Thirty-eight patients (72.5%) in the tHTN subgroup received modification of AHT. Calcium channel blockers (CCB) were identified as the best at controlling tHTN compared to other drugs (P = .045). The combination of AHT was more potent than a dose increase of a single-drug AHT, and early AHT intervention was more efficacious than delayed start of therapy. CONCLUSION: Patients at risk for tHTN require more rigorous blood pressure measurement. CCB seemed to be most potent and efficient, and an early combination of different classes of AHT was more efficacious than full-dose, single-agent AHT.

Antineoplásicos/efeitos adversos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Hipertensão/tratamento farmacológico , Indóis/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Pirróis/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Feminino , Humanos , Hipertensão/induzido quimicamente , Indóis/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pirróis/administração & dosagem , Estudos Retrospectivos , Sunitinibe , Resultado do Tratamento
Eur Heart J ; 30(24): 2978-84, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19773226


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.

Transplante de Medula Óssea/métodos , Infarto do Miocárdio/terapia , Adulto , Idoso , Seguimentos , Humanos , Angiografia por Ressonância Magnética , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Volume Sistólico/fisiologia , Transplante Autólogo , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/terapia