Intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: the prospective, randomized IABP SHOCK Trial for attenuation of multiorgan dysfunction syndrome.

OBJECTIVE: Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction with cardiogenic shock (CS) are often treated with intra-aortic balloon pump counterpulsation (IABP), even though the evidence to support this is limited. We determined whether IABP as an addition to PCI-centered therapy ameliorates multiorgan dysfunction syndrome (MODS) in patients with acute myocardial infarction complicated by CS. DESIGN: A prospective, randomized, controlled, open-label clinical trial recruiting patients between March 2003 and June 2004 (ClinicalTrials.gov ID NCT00469248). SETTING: Tertiary care university hospital. PATIENTS AND INTERVENTIONS: Forty-five consecutive patients with AMI and CS undergoing PCI were randomized to treatment with or without IABP. MEASUREMENTS AND MAIN RESULTS: Acute Physiology and Chronic Health Evaluation (APACHE) II scores (primary outcome measure), hemodynamic values, inflammatory markers, and plasma brain natriuretic peptide (BNP) levels (secondary outcomes) were collected over 4 days from randomization. The prospective hypothesis was that adding IABP therapy to "standard care" would improve CS-triggered MODS. The addition of IABP to standard therapy did not result in a significant improvement in MODS (measured by serial APACHE II scoring over 4 days). IABP use had no significant effect on cardiac index or systemic inflammatory activation, although BNP levels were significantly lower in IABP-treated patients. Initial and serial APACHE II scoring correlated with mortality better than cardiac index, systemic inflammatory state, and BNP levels in this group of patients. Nonsurvivors had significantly higher initial APACHE II scores (29.9 +/- 2.88) than survivors (18.1 +/- 1.66, p < .05). Nevertheless, discrepancies among patients within the groups cannot be ruled out and might interfere with our results. CONCLUSIONS: In this randomized trial addressing addition of IABP in CS patients, mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease, improvement of cardiac index, reduction of inflammatory state, or reduction of BNP biomarker status compared with medical therapy alone. However, the limitations of our present trial preclude any definitive conclusion, but request for a larger prospective, randomized, multicentered trial with mortality as primary end point.

Unilateral cerebellothalamic tract ablation in essential tremor by MRI-guided focused ultrasound.

OBJECTIVE: To report results of a prospective trial of unilateral transcranial MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract in essential tremor (ET). METHODS: This was a prospective, uncontrolled, single-center interventional study. Patients with ET fulfilling criteria for interventional therapy received unilateral ablation of the cerebellothalamic tract (CTT) by MRIgFUS. Motor symptoms, manual dexterity, cognition, and quality of life were assessed before intervention and at 48 hours and 1, 3, and 6 months after intervention. Rating of standardized video recordings was blinded for evaluation time points. Primary outcome was the change in unilateral hand tremor score of the treated hand. RESULTS: Six patients received MRIgFUS ablation of the CTT contralateral to the treated hand. Repeated-measures comparison determined a statistically significant 83% reduction (before vs 6 months after intervention mean ± SD; absolute reduction; 95% confidence interval) in the unilateral treated hand subscore (14.3 ± 4.9 vs 2.5 ± 2.6; 11.8; 8.4-15.2; p < 0.001), while quality of life improved by 52% (50.5 ± 19.4 vs 24.8 ± 11.4; 25.7; 3.5-47.28; p = 0.046). Measures for manual dexterity, attention and coordination, and overall cognition were unchanged. Transient side effects (n = 3) were ipsilateral hand clumsiness and mild gait instability for up to 3 months. CONCLUSIONS: Unilateral MRIgFUS lesioning of the CTT was highly efficacious in reducing contralateral hand tremor in ET without affecting fine motor function and dexterity over 6 months of follow-up. Adverse effects were mild and transient. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with ET, transcranial MRIgFUS ablation of the cerebellothalamic tract improves tremor.

Hemodynamic effects of intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: the prospective, randomized IABP shock trial.

We conducted the IABP Cardiogenic Shock Trial (ClinicalTrials.gov ID NCT00469248) as a prospective, randomized, monocentric clinical trial to determine the hemodynamic effects of additional intra-aortic balloon pump (IABP) treatment and its effects on severity of disease in patients with acute myocardial infarction complicated by cardiogenic shock (CS). Intra-aortic balloon pump counterpulsation is recommended in patients with CS complicating myocardial infarction. However, there are only limited randomized controlled trial data available supporting the efficacy of IABP following percutaneous coronary intervention (PCI) and its impact on hemodynamic parameters in patients with CS. Percutaneous coronary intervention of infarct-related artery was performed in 40 patients with acute myocardial infarction complicated by CS, within 12 h of onset of hemodynamic instability. Serial hemodynamic parameters were determined over the next 4 days and compared in patients receiving medical treatment alone with those treated with additional intra-aortic balloon counterpulsation. There were no significant differences among severity of disease (i.e., Acute Physiology and Chronic Health Evaluation II score) initially and no differences among both groups for disease improvement. We observed significant temporal improvements of cardiac output (4.8 ± 0.5 to 6.0 ± 0.5 L/min), systemic vascular resistance (926 ± 73 to 769 ± 101 dyn · s(-1) · cm(-5)), and the prognosis-validated cardiac power output (0.78 ± 0.06 to 1.01 ± 0.2 W) within the IABP group. However, there were no significant differences between the IABP group and the medical-alone group. Additional IABP treatment did not result in a significant hemodynamic improvement compared with medical therapy alone in a randomized prospective trial in patients with CS following PCI. Therefore, the use and recommendation for IABP treatment in CS remain unclear.

Interleukin-6, -7, -8 and -10 predict outcome in acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: The IABP-SHOCK-trial was a morbidity-based randomized controlled trial in patients with infarction-related cardiogenic shock (CS), which used the change of the quantified degree of multiorgan failure as determined by APACHE II score over a 4-day period as primary outcome measure. The prospective hypothesis was that adding IABP therapy to "standard care" would improve CS-triggered multi organ dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with IABP support. In an inflammatory marker substudy, we analysed the prognostic value of interleukin (IL)-1ß, -6, -7, -8, and -10 in patients with acute myocardial infarction complicated by cardiogenic shock. DESIGN: Inflammatory marker substudy of the prospective, randomized, controlled, open label IABP-SHOCK-trial (ClinicalTrials.gov ID-NCT00469248). SETTING AND METHODS: A single-center study was performed in a 12-bed Intensive-Care-Unit in an university hospital in which 40 consecutive patients were enrolled with an observational period of 96 h. RESULTS: The pro- and anti-inflammatory markers IL-6, -7, -8 and -10 showed a predictive power for mortality of infarct-related CS patients, while IL-1ß did not discriminate. The maximal values during the observational period, in case of IL-7 the minimal value, showed the best power to predict mortality. Both, ROC and multivariate analyses confirmed these suggestions (area under the curve: IL-8, 0.80 ± 0.08; IL-6, 0.79 ± 0.08; IL-10, 0.76 ± 0.08; IL-7, 0.69 ± 0.08). Inflammatory markers were not affected by the presence of IABP support. CONCLUSION: The inflammatory response in patients with myocardial infarction complicated by cardiogenic shock, as reflected by the inflammatory markers IL-6, IL-7, IL-8 and IL-10, demonstrates a clinically relevant prognostic contribution to clinical outcome.

Hemodynamic improvement following levosimendan treatment in patients with acute myocardial infarction and cardiogenic shock.

OBJECTIVES: Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with acute exacerbation of congestive heart failure. We wanted to determine the hemodynamic effects of levosimendan following ineffective conventional therapy (with catecholamines) in patients with cardiogenic shock following myocardial infarction. DESIGN: Observational hemodynamic study. SETTING: Tertiary care center university hospital. PATIENTS: Fifty-six patients with cardiogenic shock secondary to myocardial infarction were treated with percutaneous revascularization (intra-aortic balloon pump where appropriate) and commenced on conventional inotropic therapy. INTERVENTIONS: Patients with persisting cardiogenic shock 24 hrs after revascularization were additionally treated with levosimendan (rapid bolus of 12 microg/kg for 10 mins, then 0.05-0.2 mug/kg/min for 24 hrs) (n = 25). MEASUREMENTS AND MAIN RESULTS: With conventional catecholamine therapy (norepinephrine and dobutamine), we observed only marginal improvement in mean arterial pressure or cardiac index. In contrast, the addition of levosimendan produced a significant increase in cardiac index (2.1 +/- 0.56 to 3.0 +/- 1.11 L/min/m2, p < .01) and cardiac power index (0.32 +/- 0.08 to 0.44 +/- 0.18 W, p < .01), whereas systemic vascular resistance decreased significantly (1208 +/- 333 to 858 +/- 299 dyne.sec.cm(-5), p < .01). There was no significant change in blood pressure during levosimendan treatment. Hemodynamic improvement was sustained after levosimendan infusion was stopped. CONCLUSIONS: Levosimendan infusion in cardiogenic shock following acute myocardial infarction improved cardiovascular hemodynamics without leading to hypotension.