René J. van der Schaaf

A systematic review and meta-analysis of intra-aortic balloon pump therapy in ST-elevation myocardial infarction : should we change the guidelines?

Aims Intra-aortic balloon counterpulsation (IABP) in ST-segment elevation myocardial infarction (STEMI) with cardiogenic shock is strongly recommended (class IB) in the current guidelines. We performed meta-analyses to evaluate the evidence for IABP in STEMI with and without cardiogenic shock. Methods and results Medical literature databases were scrutinized to identify randomized trials comparing IABP with no IABP in STEMI. In absence of randomized trials, cohort studies of IABP in STEMI with cardiogenic shock were identified. Two separate meta-analyses were performed respectively. The first meta-analysis included seven randomized trials (n = 1009) of STEMI. IABP showed neither a 30-day survival benefit nor improved left ventricular ejection fraction, while being associated with significantly higher stroke and bleeding rates. The second meta-analysis included nine cohorts of STEMI patients with cardiogenic shock (n = 10529). In patients treated with thrombolysis, IABP was associated with an 18% [95% confidence interval (CI), 16-20%; P < 0.0001] decrease in 30 day mortality, albeit with significantly higher revascularization rates compared to patients without support. Contrariwise, in patients treated with primary percutaneous coronary intervention, IABP was associated with a 6% (95% CI, 3-10%; P < 0.0008) increase in 30 day mortality. Conclusion The pooled randomized data do not support IABP in patients with high-risk STEMI. The meta-analysis of cohort studies in the setting of STEMI complicated by cardiogenic shock supported IABP therapy adjunctive to thrombolysis. In contrast, the observational data did not support IABP therapy adjunctive to primary PCI. All available observational data concerning IABP therapy in the setting of cardiogenic shock is importantly hampered by bias and confounding. There is insufficient evidence endorsing the current guideline recommendation for the use of IABP therapy in the setting of STEMI complicated by cardiogenic shock. Our meta-analyses challenge the current guideline recommendations.

Bioresorbable Scaffolds versus Metallic Stents in Routine PCI

BACKGROUND Bioresorbable vascular scaffolds were developed to overcome the shortcomings of drug‐eluting stents in percutaneous coronary intervention (PCI). We performed an investigator‐initiated, randomized trial to compare an everolimus‐eluting bioresorbable scaffold with an everolimus‐eluting metallic stent in the context of routine clinical practice. METHODS We randomly assigned 1845 patients undergoing PCI to receive either a bioresorbable vascular scaffold (924 patients) or a metallic stent (921 patients). The primary end point was target‐vessel failure (a composite of cardiac death, target‐vessel myocardial infarction, or target‐vessel revascularization). The data and safety monitoring board recommended early reporting of the study results because of safety concerns. This report provides descriptive information on end‐point events. RESULTS The median follow‐up was 707 days. Target‐vessel failure occurred in 105 patients in the scaffold group and in 94 patients in the stent group (2‐year cumulative event rates, 11.7% and 10.7%, respectively; hazard ratio, 1.12; 95% confidence interval [CI], 0.85 to 1.48; P=0.43); event rates were based on Kaplan–Meier estimates in time‐to‐event analyses. Cardiac death occurred in 18 patients in the scaffold group and in 23 patients in the stent group (2‐year cumulative event rates, 2.0% and 2.7%, respectively), target‐vessel myocardial infarction occurred in 48 patients in the scaffold group and in 30 patients in the stent group (2‐year cumulative event rates, 5.5% and 3.2%), and target‐vessel revascularization occurred in 76 patients in the scaffold group and in 65 patients in the stent group (2‐year cumulative event rates, 8.7% and 7.5%). Definite or probable device thrombosis occurred in 31 patients in the scaffold group as compared with 8 patients in the stent group (2‐year cumulative event rates, 3.5% vs. 0.9%; hazard ratio, 3.87; 95% CI, 1.78 to 8.42; P<0.001). CONCLUSIONS In this preliminary report of a trial involving patients undergoing PCI, there was no significant difference in the rate of target‐vessel failure between the patients who received a bioresorbable scaffold and the patients who received a metallic stent. The bioresorbable scaffold was associated with a higher incidence of device thrombosis than the metallic stent through 2 years of follow‐up. (Funded by Abbott Vascular; AIDA ClinicalTrials.gov number, NCT01858077.)

Presence of Older Thrombus Is an Independent Predictor of Long-Term Mortality in Patients With ST-Elevation Myocardial Infarction Treated With Thrombus Aspiration During Primary Percutaneous Coronary Intervention

Background— Routine thrombus aspiration is frequently used during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction to prevent distal embolization. Recently, evidence of clinical benefit was published. In 50% of the ST-elevation myocardial infarction patients with an onset of symptoms <12 hours before, thrombi were shown to be >1 day old. This observation illustrates that plaque rupture and coronary occlusion are significantly separated in time. In the present study, we correlate the presence of fresh versus older thrombus with long-term mortality. Methods and Results— Thrombus aspiration was performed in 1315 patients treated with primary percutaneous coronary intervention with 3 devices (Rescue, Export, and Proxis). Aspirated material was fixed in formalin and processed for histopathology. If possible, thrombus age was classified as either fresh only (<1 day) or older (>1 day). We identified fresh thrombus in 552 patients and older thrombus in 372 patients. The cumulative Kaplan-Meier estimate of all-cause mortality at 4 years was significantly higher in patients with older thrombus (16.0%) compared with patients with fresh thrombus (7.4%), with a hazard ratio of 1.82 (95% confidence interval, 1.17 to 2.85; P=0.008). Multivariate analysis identified the presence of older thrombus, in addition to other established predictors, as an independent predictor (hazard ratio, 1.83; 95% confidence interval, 1.14 to 2.93; P=0.01) of long-term mortality. Conclusion— Our study demonstrates that the presence of older thrombus, in addition to other established predictors, is an independent predictor of long-term mortality in patients with ST-elevation myocardial infarction treated with thrombus aspiration during primary percutaneous coronary intervention.

Effects of left ventricular unloading by Impella Recover LP2.5 on coronary hemodynamics

We studied the effects of LV unloading by the Impella on coronary hemodynamics by simultaneously measuring intracoronary pressure and flow and the derived parameters fractional flow reserve (FFR), coronary flow velocity reserve (CFVR), and coronary microvascular resistance (MR).

Left ventricular unloading in acute ST-segment elevation myocardial infarction patients is safe and feasible and provides acute and sustained left ventricular recovery

To the Editor: Unloading the left ventricle (LV) after ST-segment elevation myocardial infarction (STEMI) in addition to reperfusion therapy may reduce infarct size and may give the myocardium time to recuperate from ischemic stunning ([1][1]). This may be particularly true in STEMI patients with

Effect of Multivessel Coronary Disease With or Without Concurrent Chronic Total Occlusion on One-Year Mortality in Patients Treated With Primary Percutaneous Coronary Intervention for Cardiogenic Shock

Despite early revascularization, mortality remains high in patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock. It has been shown that the effect of multivessel disease (MVD) on mortality in patients with STEMI treated with primary percutaneous coronary intervention is mainly caused by the presence of chronic total occlusion (CTO) in a noninfarct-related coronary artery. Whether this association also exists in patients with STEMI with cardiogenic shock is unknown. In our institution, 292 consecutive patients with STEMI complicated by cardiogenic shock were admitted from 1997 to 2005 and treated with primary percutaneous coronary intervention. Patients were classified as having single vessel disease, MVD without CTO, and CTO. Cox regression analysis was used for multivariate analysis. The 1-year mortality rate of patients with single-vessel disease, MVD, and CTO was 31%, 47%, and 63%, respectively. After adjustment for possible confounders, MVD alone was not an independent predictor of 1-year mortality (hazard ratio 1.5, 95% confidence interval 0.98 to 2.3, p = 0.07). In contrast, CTO in a noninfarct-related artery was an independent predictor of 1-year mortality (hazard ratio 2.1, 95% confidence interval 1.5 to 3.1, p <0.01). In conclusion, the presence of CTO in a non-infarct-related artery was an independent predictor of 1-year mortality. In contrast, MVD alone lost its predictive significance after multivariate analysis.

Relation between the assessment of microvascular injury by cardiovascular magnetic resonance and coronary Doppler flow velocity measurements in patients with acute anterior wall myocardial infarction.

OBJECTIVES We studied the relation between presence and severity of microvascular obstruction (MO), measured by cardiovascular magnetic resonance (CMR) and intracoronary Doppler flow measurements, for assessment of myocardial reperfusion in patients with acute anterior myocardial infarction (MI) treated by primary percutaneous coronary intervention (PCI). BACKGROUND Cardiovascular magnetic resonance has been used to detect and quantify MO in patients after acute MI but has never been compared with coronary blood flow velocity patterns. METHODS Twenty-seven patients with first anterior ST-segment elevation MI successfully treated with primary PCI were included. Coronary blood flow velocity was measured during recatheterization 4 to 8 days after primary PCI. These measurements were related to MO determined by late gadolinium-enhanced (LGE) CMR performed the day before recatheterization. RESULTS Early systolic retrograde flow was observed in 0 of 8 patients without MO on LGE CMR and in 10 (53%) of 19 patients with MO (p = 0.01). The extent of MO correlated with the diastolic-systolic velocity ratio (r = 0.44; p = 0.02), diastolic deceleration time (r = -0.61; p = 0.001), diastolic deceleration rate (r = 0.75; p < 0.0001), and coronary flow velocity reserve of the infarct-related artery (r = -0.44; p = 0.02). Furthermore, multivariate regression analyses, including extent of MO, infarct size, and transmural necrosis on LGE CMR, revealed that extent of MO was the only independent factor related to early systolic retrograde flow and diastolic deceleration rate. CONCLUSIONS Assessment of microvascular injury by LGE CMR corresponds well to evaluation by intracoronary Doppler flow measurements. By means of CMR, quantification of myocardial function, infarct size, and microvascular injury can accurately be performed with a single noninvasive technique in patients with acute MI.

Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

BackgroundIn the setting of primary percutaneous coronary intervention, patients with a chronic total occlusion in a non-infarct related artery were recently identified as a high-risk subgroup. It is unclear whether ST-elevation myocardial infarction patients with a chronic total occlusion in a non-infarct related artery should undergo additional percutaneous coronary intervention of the chronic total occlusion on top of optimal medical therapy shortly after primary percutaneous coronary intervention. Possible beneficial effects include reduction in adverse left ventricular remodeling and preservation of global left ventricular function and improved clinical outcome during future coronary events.Methods/DesignThe Evaluating Xience V and left ventricular function in Percutaneous coronary intervention on occLusiOns afteR ST-Elevation myocardial infarction (EXPLORE) trial is a randomized, prospective, multicenter, two-arm trial with blinded evaluation of endpoints. Three hundred patients after primary percutaneous coronary intervention for ST-elevation myocardial infarction with a chronic total occlusion in a non-infarct related artery are randomized to either elective percutaneous coronary intervention of the chronic total occlusion within seven days or standard medical treatment. When assigned to the invasive arm, an everolimus-eluting coronary stent is used. Primary endpoints are left ventricular ejection fraction and left ventricular end-diastolic volume assessed by cardiac Magnetic Resonance Imaging at four months. Clinical follow-up will continue until five years.DiscussionThe ongoing EXPLORE trial is the first randomized clinical trial powered to investigate whether recanalization of a chronic total occlusion in a non-infarct related artery after primary percutaneous coronary intervention for ST-elevation myocardial infarction results in a better preserved residual left ventricular ejection fraction, reduced end-diastolic volume and enhanced clinical outcome.Trial registrationtrialregister.nl NTR1108.

Randomized Comparison of Primary Percutaneous Coronary Intervention With Combined Proximal Embolic Protection and Thrombus Aspiration Versus Primary Percutaneous Coronary Intervention Alone in ST-Segment Elevation Myocardial Infarction: The PREPARE (PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-Elevation) Study

OBJECTIVES The purpose of this study was to evaluate the effectiveness of combined proximal embolic protection with thrombus aspiration (Proxis Embolic Protection System [St. Jude Medical, St. Paul, Minnesota]) in ST-segment elevation myocardial infarction patients. BACKGROUND Embolization during primary percutaneous coronary intervention (PCI) may result in microvascular obstruction, reduced myocardial perfusion, and impaired prognosis. METHODS Two hundred eight-four patients were randomized to primary PCI with the Proxis system versus primary PCI alone after angiography. The primary end point was the occurrence of complete (> or =70%) ST-segment resolution (STR) at 60 min measured by continuous ST-segment Holter. RESULTS There was no significant difference in the occurrence of the primary end point (80% vs. 72%, p = 0.14). However, immediate complete STR (at time of last contrast) occurred in 66% of Proxis-treated patients and 50% in control patients (absolute difference, 16.3%; 95% confidence interval: 4.3% to 28.2%; p = 0.009). A significant lower ST-segment curve area (0 to 3 h after primary PCI) was observed in the Proxis arm (5,192 microV/min vs. 6,250 microV/min, p = 0.037). Major adverse cardiac and cerebral events at 30 days occurred with similar frequency in both groups (6 vs. 10). CONCLUSIONS There was no significant difference in complete STR at 60 min in this proof-of-concept study. However, we observed a significant difference in immediate complete STR in Proxis-treated patients, better STR at later time points, and a reduction of electrocardiogram injury current over time, compared with control patients. The results suggest that primary PCI with the Proxis system may lead to better immediate microvascular flow in ST-segment elevation myocardial infarction patients. (The PREPARE Study; ISRCTN71104460).

Interferon-β Signaling Is Enhanced in Patients With Insufficient Coronary Collateral Artery Development and Inhibits Arteriogenesis in Mice

Stimulation of collateral artery growth in patients has been hitherto unsuccessful, despite promising experimental approaches. Circulating monocytes are involved in the growth of collateral arteries, a process also referred to as arteriogenesis. Patients show a large heterogeneity in their natural arteriogenic response on arterial obstruction. We hypothesized that circulating cell transcriptomes would provide mechanistic insights and new therapeutic strategies to stimulate arteriogenesis. Collateral flow index was measured in 45 patients with single-vessel coronary artery disease, separating collateral responders (collateral flow index, >0.21) and nonresponders (collateral flow index, ≤0.21). Isolated monocytes were stimulated with lipopolysaccharide or taken into macrophage culture for 20 hours to mimic their phenotype during arteriogenesis. Genome-wide mRNA expression analysis revealed 244 differentially expressed genes (adjusted P, <0.05) in stimulated monocytes. Interferon (IFN)-β and several IFN-related genes showed increased mRNA levels in 3 of 4 cellular phenotypes from nonresponders. Macrophage gene expression correlated with stimulated monocytes, whereas resting monocytes and progenitor cells did not display differential gene regulation. In vitro, IFN-β dose-dependently inhibited smooth muscle cell proliferation. In a murine hindlimb model, perfusion measured 7 days after femoral artery ligation showed attenuated arteriogenesis in IFN-β–treated mice compared with controls (treatment versus control: 31.5±1.2% versus 41.9±1.9% perfusion restoration, P<0.01). In conclusion, patients with differing arteriogenic response as measured with collateral flow index display differential transcriptomes of stimulated monocytes. Nonresponders show increased expression of IFN-β and its downstream targets, and IFN-β attenuates proliferation of smooth muscle cells in vitro and hampers arteriogenesis in mice. Inhibition of IFN-β signaling may serve as a novel approach for the stimulation of collateral artery growth.