Peter W. Radke

Mild therapeutic hypothermia in patients after out-of-hospital cardiac arrest due to acute ST-segment elevation myocardial infarction undergoing immediate percutaneous coronary intervention.

Objective:Mild therapeutic hypothermia (MTH) has been integrated into international resuscitation guidelines. In the majority of patients, sudden cardiac arrest is caused by myocardial infarction. This study investigated whether a combination of MTH with primary percutaneous coronary intervention (PCI) is feasible, safe, and potentially beneficial in patients after cardiac arrest due to acute myocardial infarction. Design:Single-center observational study with a historical control group. Setting:University clinic. Patients:Thirty-three patients after cardiac arrest with ventricular fibrillation as initial rhythm and restoration of spontaneous circulation who remained unconscious at admission and presented with acute ST elevation myocardial infarction (STEMI). Interventions:In 16 consecutive patients (2005–2006), MTH was initiated immediately after admission and continued during primary PCI. Seventeen consecutive patients who were treated in a similar 2-yr observation interval before implementation of MTH (2003–2004) served as a control group. Feasibility, safety, mortality, and neurologic outcome were documented. Measurements and Main Results:Initiation of MTH did not result in longer door-to-balloon times compared with the control group (82 vs. 85 mins), indicating that implementation of MTH did not delay the onset of primary PCI. Target temperature (32–34°C) in the MTH group was reached within 4 hrs, consistent with previous trials and suggesting that primary PCI did not affect the velocity of cooling. Despite a tendency to increased bleeding complications and infections, patients treated with MTH tended to have a lower mortality after 6 months (25% vs. 35%, p = .71) and an improved neurologic outcome as determined by a Glasgow-Pittsburgh Cerebral Performance Scale score of 1 or 2 (69% vs. 47% in the control group, p = .30). Conclusions:MTH in combination with primary PCI is feasible and safe in patients resuscitated after cardiac arrest due to acute myocardial infarction. A combination of these therapeutic procedures should be strongly considered as standard therapy in patients after out-of-hospital cardiac arrest due to STEMI.

Evaluation of the SOFA score: a single-center experience of a medical intensive care unit in 303 consecutive patients with predominantly cardiovascular disorders

Objective: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score, the total maximum SOFA (TMS) score, and a derived variable, the ΔSOFA (TMS score minus total SOFA score on day 1) in medical, cardiovascular patients as a means for describing the incidence and severity of organ dysfunction and the prognostic value regarding outcome. Design: Prospective, clinical study. Setting: Medical intensive care unit in a university hospital. Patients: A total of 303 consecutive patients were included (216 men, 87 women; mean age 62 ± 12.6 years; SAPS II 26.2 ± 12.7). They were evaluated 24 h after admission and thereafter every 24 h until ICU discharge or death between November 1997 and March 1998. Readmissions and patients with an ICU stay shorter than 12 h were excluded. Main outcome measure: Survival status at hospital discharge, incidence of organ dysfunction/failure. Interventions: Collection of clinical and demographic data and raw data for the computation of the SOFA score every 24 h until ICU discharge. Measurements and main results: Length of ICU stay was 3.7 ± 4.7 days. ICU mortality was 8.3 % and hospital mortality 14.5 %. Nonsurvivors had a higher total SOFA score on day 1 (5.9 ± 3.7 vs. 1.9 ± 2.3, p < 0.001) and thereafter until day 8. High SOFA scores for any organ system and increasing number of organ failures (SOFA score ≥ 3) were associated with increased mortality. Cardiovascular and neurological systems (day 1) were related to outcome and cardiovascular and respiratory systems, and admission from another ICU to length of ICU stay. TMS score was higher in nonsurvivors (1.76 ± 2.55 vs. 0.58 ± 1.39, p < 0.01), and ΔSOFA/total SOFA on day 1 was independently related to outcome. The area under the receiver-operating characteristic curve was 0.86 for TMS, 0.82 for SOFA on day 1, and 0.77 for SAPS II. Conclusions: The SOFA, TMS, and ΔSOFA scores provide the clinician with important information on degree and progression of organ dysfunction in medical, cardiovascular patients. On day 1 both SOFA score and TMS score had a better prognostic value than SAPS II score. The model is closely related to outcome and identifies patients who are at increased risk for prolonged ICU stay.

Long-term prognosis of the transient left ventricular dysfunction syndrome (Tako-Tsubo cardiomyopathy) : Focus on malignancies

The pathophysiology and long‐term prognosis of the transient left ventricular dysfunction syndrome (LVDS, Tako‐Tsubo cardiomyopathy) is largely unknown.

Outcome after treatment of coronary in-stent restenosis; results from a systematic review using meta-analysis techniques.

AIMS To evaluate the clinical outcome after treatment of coronary in-stent restenosis. METHODS AND RESULTS For identification of the relevant literature a specific search strategy was conducted and explicit inclusion criteria were defined to avoid selection bias. Based on the selected literature, a systematic review using descriptive statistics and meta-analysis methods regarding the outcome after treatment of coronary in-stent restenosis was performed. The proportion of patients experiencing a major adverse cardiac event (MACE) as defined by death, myocardial infarction, and target lesion revascularization was the main outcome measure. A total of 1304 citations were identified. Among these, 28 studies (six different treatment modalities) including a total of 3012 patients met the inclusion criteria and were incorporated into this analysis. The estimated average probability of experiencing a major cardiac adverse event after treatment for in-stent restenosis with a follow-up period of 9+/-4 months was 30.0% (25.0-34.9%, 95% confidence interval) with strong evidence for heterogeneity between study specific results (P=0.0001). The clinical outcome was not significantly different between treatment modalities. After adjustment for confounding factors (i.e. lesion length), however, patients undergoing intracoronary radiation showed an estimated advantage of 16.9% (-37.7+/-4.0%, 95% confidence interval) in MACE free survival, as compared to balloon angioplasty. The post-interventional diameter stenosis was the only independent predictor for the long-term outcome after treatment of in-stent restenosis. CONCLUSIONS Treatment of in-stent restenosis is associated with an overall 30% rate of major adverse cardiac events. Currently, repeat angioplasty is the treatment option of choice, especially when a sufficient acute procedural result can be achieved. Intracoronary radiation should be considered in cases with therapy refractory forms of diffuse in-stent restenosis.

Influence of a platelet GPIIb/IIIa receptor antagonist on myocardial hypoperfusion during rotational atherectomy as assessed by myocardial Tc-99m sestamibi scintigraphy

OBJECTIVES This study evaluated the effect of the glycoprotein IIb/IIIa (GPIIb/IIIa) antagonist abciximab on myocardial hypoperfusion during percutaneous transluminal rotational atherectomy (PTRA). BACKGROUND PTRA may cause transient ischemia and periprocedural myocardial injury. A platelet-dependent risk of non-Q-wave infarctions after directional atherectomy has been described. The role of platelets for the incidence and severity of myocardial hypoperfusion during PTRA is unknown. METHODS Seventy-five consecutive patients with complex lesions were studied using resting Tc-99m sestamibi single-photon emission computed tomography prior to PTRA, during, and 2 days after the procedure. The last 30 patients received periprocedural abciximab (group A) and their results were compared to the remaining 45 patients (group B). For semiquantitative analysis, myocardial perfusion in 24 left ventricular regions was expressed as percentage of maximal sestamibi uptake. RESULTS Baseline characteristics did not differ between the groups. Transient perfusion defects were observed in 39/45 (87%) patients of group B, but only in 10/30 (33%) patients of group A (p < 0.001). Perfusion was significantly reduced during PTRA in 3.3 +/- 2.5 regions in group B compared to 1.4 +/- 2.5 regions in group A (p < 0.01). Perfusion in the region with maximal reduction during PTRA in groups B and A was 76 +/- 15% and 76 +/- 15% at baseline, decreased to 56 +/- 16% (p < 0.001) and 67 +/- 14%, respectively, during PTRA (p < 0.01 A vs. B), and returned to 76 +/- 15% and 80 +/- 13%, respectively, after PTRA. Nine patients in group B (20%) and two patients in group A (7%) had mild creatine kinase and/or troponin t elevations (p = 0.18). Patients with elevated enzymes had larger perfusion defects than did patients without myocardial injury (4.2 +/- 2.7 vs. 2.3 +/- 2.5 regions, p < 0.05). CONCLUSIONS These data indicate that GPIIb/IIIa blockade reduces incidence, extent and severity of transient hypoperfusion during PTRA. Thus, platelet aggregation may play an important role for PTRA-induced hypoperfusion.

Comparative assessment of drug-eluting balloons in an advanced porcine model of coronary restenosis

The advent of drug-eluting balloon (DEB) therapy has represented an important development in interventional cardiology. Nevertheless, preclinical data with this technology remain scant, and comparative studies have not previously been published. Bare metal stents were implanted in the coronary arteries of 15 pigs followed by balloon angioplasty. Animals were allocated to treatment with a 60-second inflation of one of four different balloon catheters: a conventional untreated plain angioplasty balloon (PBA, Biotronik AG), the Pantera Lux DEB (3.0 μg/mm2 paclitaxel; BTHC excipient, Biotronik AG), the Elutax DEB (2.0 μg/mm2 paclitaxel; no excipient; Aachen Resonance), or the SeQuent Please DEB (3.0 μg/mm2 paclitaxel; iopromide excipient: B. Braun). Twenty-eight days following balloon deployment, animals underwent repeat angiography for quantitative coronary angiography analysis and euthanasia for histopathologic assessment. By histology, the mean neointimal thickness was 0.44 ± 0.19 mm with PBA, 0.35 ± 0.13 mm with Pantera Lux , 0.61 ± 0.20 mm with Elutax , and 0.47 ± 0.21 mm with SeQuent Please DEB (p=0.02). In comparison with PBA, deployment of the Pantera Lux or the SeQuent Please DEB resulted in delayed healing characterised by significant increases in fibrin, neointimal cell vacuity and delayed re-endothelialisation. In conclusion, investigation of comparative DEB performance in a porcine model of advanced coronary restenosis reveals significant heterogeneity of neointimal suppression between the devices tested with numerically lowest values seen in the Pantera Lux group. On the other hand, evidence of delayed healing was observed in the most effective DEB groups.

Vascular effects of paclitaxel following drug-eluting balloon angioplasty in a porcine coronary model: the importance of excipients

AIMS The vascular effects of drug- eluting balloon (DEB) deployment in the absence of coronary stents have not been characterised. This study evaluated potential vascular effects of paclitaxel-coated angioplasty balloons using different excipients in the absence of additional stents. METHODS AND RESULTS A total 45 porcine arteries were treated with paclitaxel-coated DEBs using four different excipients (all 3.0 µg/mm2): A) iopromide (n=9), B) ATEC excipient (n=8), C) BTHC excipient (n=10), D) lecithine excipient (n=10). Uncoated bare angioplasty balloons served as controls (n=8). Histology, histomorphometry, and quantitative angiography analysis were performed 28 days following intervention. Tissue concentrations of paclitaxel were measured in selected animals using BTHC excipient (n=39 arteries) and reached maximum concentrations of 165 ng/mg 30 min after delivery in coronary target tissue. There were no differences in efficacy endpoints using histomorphology or quantitative angiography between groups. In contrast, however, treatment with DEBs using BTHC excipient or iopromide was associated with increased fibrin deposition and inflammation indicating delayed vascular healing. DEBs using lecithin excipient or uncoated angioplasty balloons did not induce any comparable vascular effects. CONCLUSIONS Effective excipients are necessary to accomplish successful balloon facilitated paclitaxel delivery, which is associated with delayed vascular healing as a sign of successful drug transfer. The potential of DEBs to diminish restenosis following angioplasty may be insufficient in the absence of additional stents.

Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial

AIMS Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). METHODS AND RESULTS A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed. CONCLUSIONS Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.

Endeavour zotarolimus-eluting stent reduces stent thrombosis and improves clinical outcomes compared with cypher sirolimus-eluting stent: 4-year results of the PROTECT randomized trial

AIMS To compare the long-term clinical safety between two drug-eluting stents with different healing characteristics in the Patient Related Outcomes with Endeavour (E-ZES) vs. Cypher (C-SES) Stenting Trial (PROTECT). At 3 years, there was no difference in the primary outcome of definite or probable stent thrombosis or in the other main secondary clinical outcomes consisting of the composite of death or myocardial infarction (MI). Prespecified 4-year clinical follow-up was analysed. METHODS AND RESULTS Patient Related OuTcomes with Endeavour vs. Cypher Stenting Trial was a prospective, open-label randomized-controlled superiority trial powered to look at differences in long-term clinical safety, including stent thrombosis. Dual antiplatelet therapy (DAPT) was prescribed for ≥ 3 months and up to 12 months based on current guidelines. Patient Related OuTcomes with Endeavour vs. Cypher Stenting Trial enrolled 8791 patients undergoing elective or emergency PCI to E-ZES or C-SES. There was no difference in DAPT usage between the two groups up to 4 years. At 4-year follow-up, the primary outcome occurred in 1.6% of E-ZES vs. 2.6% of C-SES patients [HR 0.63 (95% CI 0.46-0.85), P = 0.003]. The composite of all-cause death or large MI occurred in 6.7% of E-ZES vs. 8.0% of C-SES-treated patients [HR 0.84 (95% CI 0.71-0.98), P = 0.024]. CONCLUSIONS Drug-eluting coronary stents with different healing characteristics demonstrated different late safety profiles: after 4 years, compared with C-SES, E-ZES reduced the risk of stent thrombosis and the risk of the composite endpoints of death or MI. Appropriately powered large-scale trials with long-term follow-up are critical to determine clinical safety and efficacy of permanently implanted coronary stents. This trial is registered with ClinicalTrials.gov, number NCT00476957.

Sirolimus- and paclitaxel-eluting stents in comparison with balloon angioplasty for treatment of in-stent restenosis.

This study evaluated the acute and follow‐up effectiveness of sirolimus‐eluting stents (SESs) and nonpolymer‐based paclitaxel‐eluting stents (PESs) in comparison will balloon angioplasty for treatment of complex in‐stent restenosis (ISR) lesions. Drug‐eluting stents have been demonstrated to be highly effective for treatment of de novo lesions. The use of drug‐eluting stents for treatment of complex ISR is less well defined. Eighty one lesions with in‐stent restenosis (lesion length < 30 mm in a native coronary artery) were treated with either PTCA alone (n = 26 lesions in 25 patients), PES (n = 27 lesions in 24 patients; Achieve, Cook; 3,1 μg paclitaxel/mm2 nonpolymer‐based coating), SES (n = 28 lesions in 28 patients; Cypher, Cordis; 140 μg sirolimus/cm2 metal surface area). Nine‐month MACE rates were 32%, 8%, and 14% (all due to repeated revascularization procedures, except one death in the SES group) in the PTCA, PES, and SES group, respectively. Postintervention minimal lumen diameter in stent was significantly greater in the SES and the PES group in comparison with the PTCA group (2.37 ± 0.26, 2.54 ± 0.42, 1.78 ± 0.23 mm; P < 0.001). At 6‐month angiographic follow‐up, late loss in stent was 0.77 ± 0.45, 0.43 ± 0.53, and 0.29 ± 0.52 mm for the PTCA, PES, and SES group, respectively (P = 0.005). In‐lesion restenosis rate was 61% for the PTCA group, 20% for the PES group, and 13% for the SES group (P = 0.042). The implantation of SES as well as nonpolymer PES proved to be effective for treatment of ISR. The combination of improved acute gain and reduced late loss results in a significantly improved angiographic follow‐up result in comparison with PTCA. Catheter Cardiovasc Interv 2005;64:28–34.