Tim P van de Hoef

Heart Centre Hasselt, Горад Хасельт, Overijssel, Netherlands

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Publications (89)

  • Tim P. van de Hoef · Ricardo Petraco · Martijn A. van Lavieren · [...] · Jan J. Piek
    Article · Jun 2016 · EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
  • Tim P. van de Hoef · Javier Escaned · Jan J. Piek
    Article · Jan 2016 · JACC Cardiovascular Interventions
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    Ivo A.C. van der Bilt · Jean-Paul Vendeville · Tim P. van de Hoef · [...] · Hans W.M. Niessen
    [Show abstract] [Hide abstract] ABSTRACT: Cardiac abnormalities after subarachnoid hemorrhage (SAH) such as electrocardiographic changes, echocardiographic wall motion abnormalities, and elevated troponin levels are independently associated with a poor prognosis. They are caused by catecholaminergic stress coinciding with influx of inflammatory cells into the heart. These abnormalities could be a sign of a myocarditis, potentially giving insight in pathophysiology and treatment options. These inflammatory cells are insufficiently characterized, and it is unknown whether myocarditis is associated with SAH. Myocardium of 25 patients who died of SAH and 18 controls was stained with antibodies identifying macrophages (CD68), lymphocytes (CD45), and neutrophil granulocytes (myeloperoxidase). Myocytolysis was visualized using complement staining (C3d). CD31 was used to identify putative thrombi. We used Mann-Whitney U testing for analysis.
    Full-text available · Article · Dec 2015 · Journal of critical care
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    Tim P van de Hoef · Martijn Meuwissen · Jan J Piek
    [Show abstract] [Hide abstract] ABSTRACT: Fractional flow reserve (FFR) is a well-validated clinical coronary physiological parameter derived from the measurement of coronary pressures and has drastically changed revascularization decision-making in clinical practice. Nonetheless, it is important to realize that FFR is a coronary pressure-derived estimate of coronary blood flow impairment. It is thereby not the same as direct measures of coronary flow impairment that determine the occurrence of signs and symptoms of myocardial ischemia. This consideration is important, since the FAME 2 study documented a limited discriminatory power of FFR to identify stenoses that require revascularization to prevent adverse events. The physiological difference between FFR and direct measures of coronary flow impairment may well explain the findings in FAME 2. This review aims to address the physiological background of FFR, its ambiguities, and its consequences for the application of FFR in clinical practice, as well as to reinterpret the diagnostic and prognostic characteristics of FFR in the light of the recent FAME 2 trial outcomes.
    Full-text available · Article · Dec 2015 · Vascular Health and Risk Management
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    [Show abstract] [Hide abstract] ABSTRACT: Background Our understanding of human coronary physiological behaviour is derived from animal models. We sought to describe physiological behaviour across a large collection of invasive pressure and flow velocity measurements, to provide a better understanding of the relationships between these physiological parameters and to evaluate the rationale for resting stenosis assessment. Methods and results Five hundred and sixty-seven simultaneous intracoronary pressure and flow velocity assessments from 301 patients were analysed for coronary flow velocity, trans-stenotic pressure gradient (TG), and microvascular resistance (MVR). Measurements were made during baseline and hyperaemic conditions. The whole cardiac cycle and the diastolic wave-free period were assessed. Stenoses were assessed according to fractional flow reserve (FFR) and quantitative coronary angiography DS%. With progressive worsening of stenoses, from unobstructed angiographic normal vessels to those with FFR ≤ 0.50, hyperaemic flow falls significantly from 45 to 19 cm/s, Ptrend < 0.001 in a curvilinear pattern. Resting flow was unaffected by stenosis severity and was consistent across all strata of stenosis (Ptrend > 0.05 for all). Trans-stenotic pressure gradient rose with stenosis severity for both rest and hyperaemic measures (Ptrend < 0.001 for both). Microvascular resistance declines with stenosis severity under resting conditions (Ptrend < 0.001), but was unchanged at hyperaemia (2.3 ± 1.1 mmHg/cm/s; Ptrend = 0.19). Conclusions With progressive stenosis severity, TG rises. However, while hyperaemic flow falls significantly, resting coronary flow is maintained by compensatory reduction of MVR, demonstrating coronary auto-regulation. These data support the translation of coronary physiological concepts derived from animals to patients with coronary artery disease and furthermore, suggest that resting pressure indices can be used to detect the haemodynamic significance of coronary artery stenoses.
    Full-text available · Article · Nov 2015 · European Heart Journal
  • Mauro Echavarría Pinto · Tim P van de Hoef · Martijn A. van Lavieren · [...] · Javier Escaned
    [Show abstract] [Hide abstract] ABSTRACT: OBJECTIVES This study sought to understand the physiological basis of baseline distal-to-aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) agreement and discordance, using coronary flow reserve (CFR), stenosis resistance, and microcirculatory resistance measurements, and form there, to investigate the potential value of combining Pd/Pa with FFR in the diagnostic rationale. BACKGROUND Pd/Pa is always available before FFR assessment, and emerging data supports the notion that baseline indices can determine the ischemic potential of coronary stenosis in selected subsets. METHODS A total of 467 stenosed vessels from 363 patients were investigated with pressure and flow sensors during baseline and hyperemia: 168 vessels (135 patients) with thermodilution-derived flow, and 299 vessels (228 patients) with Doppler-derived flow. RESULTS Pd/Pa correlated more strongly with CFR than FFR (rho difference = 0.129; p for rho comparison <0.001). Although Pd/Pa and FFR were closely correlated (rho = 0.798; 95% confidence interval: 0.767 to 0.828), categorical discordance was observed in 19.3% of total vessels. Such discordance was associated with the patients' clinical profile and was characterized by contrastive changes in stenosis resistance, microcirculatory resistance, and the underlying CFR. Notably, all stenosis with Pd/Pa <= 0.83 (n = 74, 15.8%) progressed to FFR <= 0.80, and although no Pd/Pa cutoff was able to exclude the development of FFR <= 0.80 in the high end of values, only 15 (10.1%) vessels with Pd/Pa >= 0.96 (n = 149, 31.9%) developed FFR <= 0.80, from which none had definite ischemia, as defined by CFR <= 1.74. CONCLUSIONS Combining baseline Pd/Pa with FFR seems to provide a more comprehensive physiological examination of stenosed coronary arteries and a closer pressure-based appraisal of the flow reserve of the downstream myocardial bed. (C) 2015 by the American College of Cardiology Foundation.
    Article · Nov 2015 · JACC Cardiovascular Interventions
  • Tim P. van de Hoef · Mauro Echavarría-Pinto · Martijn A. van Lavieren · [...] · Jan J. Piek
    [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study is to evaluate whether coronary flow capacity (CFC) improves discrimination of patients at risk for major adverse cardiac events (MACE) compared with coronary flow reserve (CFR) alone, and to study the diagnostic and prognostic implications of CFC in relation to contemporary diagnostic tests for ischemic heart disease (IHD), including fractional flow reserve (FFR). Although IHD results from a combination of focal obstructive, diffuse, and microcirculatory involvement of the coronary circulation, its diagnosis remains focused on focal obstructive causes. CFC comprehensively documents flow impairment in IHD, regardless of its origin, by interpreting CFR in relation to maximal flow (hyperemic average peak flow velocity [hAPV]), and overcomes the limitations of using CFR alone. This is governed by the understanding that ischemia occurs in vascular beds with substantially reduced hAPV and CFR, whereas ischemia is unlikely when hAPV or CFR is high. Intracoronary pressure and flow were measured in 299 vessels (228 patients), where revascularization was deferred in 154. Vessels were stratified as having normal, mildly reduced, moderately reduced, or severely reduced CFC using CFR thresholds derived from published data and corresponding hAPV percentiles. The occurrence of MACE after deferral of revascularization was recorded during 11.9 years of follow-up (quartile 1: 10.0 years, quartile 3: 13.4 years). Combining CFR and hAPV improved the prediction of MACE over CFR alone (p = 0.01). After stratification in CFC, MACE rates throughout follow-up were strongly associated with advancing impairment of CFC (p = 0.002). After multivariate adjustment, mildly and moderately reduced CFC were associated with a 2.1-fold (95% confidence interval: 1.1 to 4.0; p = 0.017), and 7.1-fold (95% confidence interval: 2.9 to 17.1; p < 0.001) increase in MACE hazard, respectively, compared with normal CFC. Severely reduced CFC was identified by FFR ≤0.80 in 90% of cases, although ≥40% of vessels with normal or mildly reduced CFC still had an FFR ≤0.80. CFC provides a cross-modality platform for the diagnosis and risk-stratification of IHD and enriches the interpretation of contemporary diagnostic tests in IHD.
    Article · Nov 2015
  • Gilbert Wijntjens · Mauro Echavarria-Pinto · Tim P. van de Hoef · [...] · Jan Piek
    Article · Oct 2015 · Journal of the American College of Cardiology
  • Mauro Echavarria-Pinto · Tim P. van de Hoef · Martijn A. van Lavieren · [...] · Javier Escaned
    [Show abstract] [Hide abstract] ABSTRACT: This study sought to understand the physiological basis of baseline distal-to-aortic pressure ratio (Pd/Pa) and fractional flow reserve (FFR) agreement and discordance, using coronary flow reserve (CFR), stenosis resistance, and microcirculatory resistance measurements, and form there, to investigate the potential value of combining Pd/Pa with FFR in the diagnostic rationale.
    Article · Oct 2015 · Journal of the American College of Cardiology
  • Kranthi K. Kolli · Tim P. van de Hoef · Mohamed A. Effat · [...] · Tarek A. Helmy
    [Show abstract] [Hide abstract] ABSTRACT: Functional assessment of intermediate coronary stenosis during cardiac catheterization is conducted using diagnostic parameters like fractional flow reserve (FFR), coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR), and hyperemic microvascular resistance (HMR). CDP (ratio of pressure drop across a stenosis to distal dynamic pressure), a nondimensional index derived from fundamental fluid dynamic principles, based on a combination of intracoronary pressure, and flow measurements may improve the functional assessment of coronary lesion severity. Patient-level data pertaining to 350 intracoronary pressure and flow measurements across coronary stenoses was assessed to evaluate CFR, FFR, HSR, HMR, and CDP. CDP was calculated as (ΔP)/(0.5 × ρ × APV2). The density of blood (ρ) was assumed to be 1.05 g/cm3. The correlation of current diagnostic parameters (CFR, FFR, HSR, and HMR) with CDP was evaluated. The receiver operating characteristic (ROC) curve was used to identify the optimal cut-off point of CDP, corresponding to the clinically used cut-off values (FFR = 0.80 and CFR = 2.0). CDP correlated significantly with FFR (r = 0.81, P < 0.05) and had significant diagnostic efficiency (ROC-area under curve of 86%), specificity (72%) and sensitivity (85%) at FFR < 0.8. The corresponding cut-off value for CDP to detect FFR < 0.8 was at CDP>25.4. CDP also correlated significantly (r = 0.98, P < 0.05) with epicardial-specific parameter, HSR. CDP, a functional parameter based on both intracoronary pressure and flow measurements, has close agreement (area under ROC curve = 86%) with FFR, the frequently used method of evaluating stenosis severity.
    Article · Sep 2015 · Catheterization and Cardiovascular Interventions
  • [Show abstract] [Hide abstract] ABSTRACT: The complexity of ischemic heart disease (IHD) comprehends disease in the succeeding perfusion domains of the vascular tree. Fractional flow reserve and coronary flow reserve are validated diagnostic modalities to identify myocardial ischemia, but solitarily do not suffice to objectify the respective contribution of obstructive and nonobstructive disease to IHD. Combined pressure and flow measurements deliver a comprehensive intracoronary assessment of IHD, although fractional flow reserve and coronary flow reserve disagree in 40% of the cases. Discrepancy between the indices does not reflect methodological failure, but explores divergent extremes of epicardial and microvascular disease, which holds vital prognostic value. We advocate critical revision of the current diagnostic and therapeutic approaches toward IHD. In this review, we deliver a perspective on the future developments in the diagnosis and treatment of IHD.
    Article · Aug 2015
  • Esther M A Wiegerinck · Tim P van de Hoef · M Cristina Rolandi · [...] · Jan Baan
    [Show abstract] [Hide abstract] ABSTRACT: Background: Aortic valve stenosis (AS) induces compensatory alterations in left ventricular hemodynamics, leading to physiological and pathological alterations in coronary hemodynamics. Relief of AS by transcatheter aortic valve implantation (TAVI) decreases ventricular afterload and is expected to improve microvascular function immediately. We evaluated the effect of AS on coronary hemodynamics and the immediate effect of TAVI. Methods and results: Intracoronary pressure and flow velocity were simultaneously assessed at rest and at maximal hyperemia in an unobstructed coronary artery in 27 patients with AS before and immediately after TAVI and in 28 patients without AS. Baseline flow velocity was higher and baseline microvascular resistance was lower in patients with AS as compared with controls, which remained unaltered post-TAVI. In patients with AS, hyperemic flow velocity was significantly lower as compared with controls (44.5±14.5 versus 54.3±18.6 cm/s; P=0.04). Hyperemic microvascular resistance (expressed in mm Hg·cm·s(-1)) was 2.10±0.69 in patients with AS as compared with 1.80±0.60 in controls (P=0.096). Coronary flow velocity reserve in patients with AS was lower, 1.9±0.5 versus 2.7±0.7 in controls (P<0.001). Improvement in coronary hemodynamics after TAVI was most pronounced in patients without post-TAVI aortic regurgitation. In these patients (n=20), hyperemic flow velocity increased significantly from 46.24±15.47 pre-TAVI to 56.56±17.44 cm/s post-TAVI (P=0.003). Hyperemic microvascular resistance decreased from 2.03±0.71 to 1.66±0.45 (P=0.050). Coronary flow velocity reserve increased significantly from 1.9±0.4 to 2.2±0.6 (P=0.009). Conclusions: The vasodilatory reserve capacity of the coronary circulation is reduced in AS. TAVI induces an immediate decrease in hyperemic microvascular resistance and a concomitant increase in hyperemic flow velocity, resulting in immediate improvement in coronary vasodilatory reserve.
    Article · Aug 2015 · Circulation Cardiovascular Interventions
  • Sukhjinder Nijjer · Guus de Waard · Tim van de Hoef · [...] · Justin Davies
    [Show abstract] [Hide abstract] ABSTRACT: Background We sought to use combined intracoronary pressure and flow velocity measurements to elucidate of the behaviour of the human coronary circulation in response to a stenosis. Methods 567 coronary vessels underwent simultaneous intracoronary pressure and flow velocity assessments, from which coronary flow velocity, transtenotic gradient (TG) and microvascular resistance (MVR) were computed. Measurements were made during rest over the whole cardiac cycle and the diastolic wave-free period (wfp), and also during adenosine-mediated hyperaemia. Stenoses was stratified according to severity as objectively determined by fractional flow reserve (FFR). Data is mean±SEM. Linear regression analysis estimated trends and P-values. Results The key results are shown in the Figure 1. As stenosis severity increases, from reference angiographically normal vessels to those with FFR≤0.50, resting flow velocity changed little (whole cycle, 18 ± 0.5 cm/s; p = 0.40, wfp, 25 ± 0.7 cm/s, p = 0.30). In contrast, hyperaemic flow falls from 45 to 19 cm/s (P < 0.01). With increasing stenosis severity, distal pressure falls such that the TG increases from 1.5 to 46 mmHg at rest (whole cycle) and 1.6 to 56 mmHg for wfp; hyperaemic TG similarly falls from 3.5 to 55 mmHg (P < 0.01 for all). Resting MVR declines as stenoses increase in severity, from 6.2 to 4.2 mmHg/cm/s at rest (P < 0.01), over the wfp from 4.4 to 2.0 mmHg/cm/s (p < 0.01); overall hyperaemic resistance was consistent across stenoses (2.3 ± 1.1 mmHg/cm/s; P = 0.19) but with a trend to suggest paradoxical vasoconstriction in severe stenoses. Conclusions With progressive stenosis severity, distal coronary pressure falls and transtenotic gradients enlarge but resting coronary flow is preserved and maintained by a compensatory reduction of microvascular resistance. This confirms coronary auto-regulation under resting conditions in humans and explains why resting pressure gradients can detect the haemodynamic stenosis significance. Resting gradients are therefore an assessment of the natural physiological response of a given coronary bed to the presence of a stenosis. This work is also pertinent for non-invasive approaches that attempt to model physiology using anatomy since we describe all three physiological parameters across a large dataset from real-world patients. Finally, the stability of resting flow across a wide-spectrum of stenoses suggests that it should be feasible to predict the change in a resting pressure index or gradient before stenting a given stenosis.
    Article · Jun 2015 · Heart (British Cardiac Society)
  • Tim P van de Hoef · Maria Siebes · Jos A E Spaan · Jan J Piek
    [Show abstract] [Hide abstract] ABSTRACT: Wide attention for the appropriateness of coronary stenting in stable ischaemic heart disease (IHD) has increased interest in coronary physiology to guide decision making. For many, coronary physiology equals the measurement of coronary pressure to calculate the fractional flow reserve (FFR). While accumulating evidence supports the contention that FFR-guided revascularization is superior to revascularization based on coronary angiography, it is frequently overlooked that FFR is a coronary pressure-derived estimate of coronary flow impairment. It is not the same as the direct measures of coronary flow from which it was derived, and which are critical determinants of myocardial ischaemia. This review describes why coronary flow is physiologically and clinically more important than coronary pressure, details the resulting limitations and clinical consequences of FFR-guided clinical decision making, describes the scientific consequences of using FFR as a gold standard reference test, and discusses the potential of coronary flow to improve risk stratification and decision making in IHD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
    Article · Jun 2015 · European Heart Journal
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    Sukhjinder S Nijjer · Ricardo Petraco · Tim P van de Hoef · [...] · Justin E Davies
    [Show abstract] [Hide abstract] ABSTRACT: Percutaneous coronary intervention (PCI) aims to increase coronary blood flow by relieving epicardial obstruction. However, no study has objectively confirmed this and assessed changes in flow over different phases of the cardiac cycle. We quantified the change in resting and hyperemic flow velocity after PCI in stenoses defined physiologically by fractional flow reserve and other parameters. Seventy-five stenoses (67 patients) underwent paired flow velocity assessment before and after PCI. Flow velocity was measured over the whole cardiac cycle and the wave-free period. Mean fractional flow reserve was 0.68±0.02. Pre-PCI, hyperemic flow velocity is diminished in stenoses classed as physiologically significant compared with those classed nonsignificant (P<0.001). In significant stenoses, flow velocity over the resting wave-free period and hyperemic flow velocity did not differ statistically. After PCI, resting flow velocity over the wave-free period increased little (5.6±1.6 cm/s) and significantly less than hyperemic flow velocity (21.2±3 cm/s; P<0.01). The greatest increase in hyperemic flow velocity was observed when treating stenoses below physiological cut points; treating stenoses with fractional flow reserve ≤0.80 gained Δ28.5±3.8 cm/s, whereas those fractional flow reserve >0.80 had a significantly smaller gain (Δ4.6±2.3 cm/s; P<0.001). The change in pressure-only physiological indices demonstrated a curvilinear relationship to the change in hyperemic flow velocity but was flat for resting flow velocity. Pre-PCI physiology is strongly associated with post-PCI increase in hyperemic coronary flow velocity. Hyperemic flow velocity increases 6-fold more when stenoses classed as physiologically significant undergo PCI than when nonsignificant stenoses are treated. Resting flow velocity measured over the wave-free period changes at least 4-fold less than hyperemic flow velocity after PCI. © 2015 American Heart Association, Inc.
    Full-text available · Article · Jun 2015 · Circulation Cardiovascular Interventions
  • Martijn A van Lavieren · Tim P van de Hoef · Krischan D Sjauw · [...] · K Lance Gould
    [Show abstract] [Hide abstract] ABSTRACT: BACKGROUND: A 66-year-old male with crescendo angina pectoris with persisting disabling angina despite optimal medical therapy. Coronary angiography in the referral hospital showed a stenosis of intermediate severity in the first diagonal branch. INVESTIGATION: Physical examination, electrocardiogram, exercise testing, transthoracic echocardiogram, coronary angiography, functional stenosis severity assessment. DIAGNOSIS: Depletion of coronary vasodilatory reserve in the presence of a focal stenosis of intermediate severity superimposed on a background of small vessel disease. MANAGEMENT: Stenting of the stenosis in the diagonal branch to increase vasodilatory reserve.
    Article · May 2015 · EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
  • [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory-based environment. Studies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons. A total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report. The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses. The ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II-ADVISE II; NCT01740895). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Article · May 2015 · JACC. Cardiovascular Interventions
  • Sukhjinder Nijjer · Guus De Waard · Tim Van De Hoef · [...] · Justin E. Davies
    Article · May 2015 · Journal of the American College of Cardiology
  • Mauro Echavarría-Pinto · Tim P van de Hoef · Hector M Garcia-Garcia · [...] · Javier Escaned
    Article · May 2015 · JACC. Cardiovascular Interventions
  • Tim P van de Hoef · Robin Nijveldt · Martin van der Ent · [...] · Jan J Piek
    [Show abstract] [Hide abstract] ABSTRACT: Pressure-controlled intermittent coronary sinus occlusion (PICSO) may improve myocardial perfusion after pPCI. We evaluated the safety and feasibility of PICSO after pPCI for STEMI, and explored its effects on infarct size and myocardial function. Thirty patients were enrolled following successful pPCI of a left anterior descending coronary artery culprit lesion for anterior STEMI, in whom PICSO for 90 minutes was attempted. Infarct size and myocardial function were assessed by cardiovascular magnetic resonance (CMR) at two to five days and four months post pPCI. An independent core laboratory selected matched historical control patients with CMR data for comparison. PICSO was initiated in 19 patients (63%), and could be maintained for 90 (±2) minutes in 12 patients (40%). Major adverse safety events occurred in one patient (3%). Comparing all PICSO-treated patients to matched controls demonstrated no significant differences in infarct size or myocardial recovery. However, infarct size reduction from two to five days to four months was greater for patients successfully treated with PICSO compared with matched controls (41.6±8.2% vs. 27.7±9.9%, respectively; p=0.04). PICSO is safe in the setting of STEMI, although feasibility was limited. Administration of sufficient PICSO therapy may be associated with enhanced myocardial recovery during follow-up, warranting further evaluation of this novel therapy.
    Article · Mar 2015 · EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology