Pressure-controlled Intermittent Coronary Sinus Occlusion Research Articles

Efficacy and safety of pressure-controlled intermittent coronary sinus occlusion in STEMI: A systematic review and meta-analysis

Efficacy and safety of pressure-controlled intermittent coronary sinus occlusion in STEMI: A systematic review and meta-analysis

A novel therapy in microvascular obstruction in ST-elevation myocardial infarction: pressure-controlled intermittent coronary sinus occlusion therapy.

Percutaneous coronary intervention has transformed the management of ST-elevation myocardial infarction (STEMI) due to a reduction in early mortality and need for repeat revascularization. However, the conventional revascularization strategy, combined with state-of-the-art anti-thrombotic and antiplatelet therapies, can still be associated with poor clinical outcome in some patients, because of reperfusion injury and microvascular obstruction contributing to the infarct size. To address this important therapeutic need, a broad-range of device-based treatments have been introduced. This is an overview of the pressure-controlled intermittent coronary sinus occlusion (PiCSO) device (Miracor Medical SA) which has been proposed for STEMI patients. PiCSO therapy could lead to an improved perfusion, decrease microvascular dysfunction, and thus potentially reduce infarct size.

Circulating microRNAs and cardiomyocyte proliferation in heart failure patients related to 10years survival.

Mechanochemical signalling drives organogenesis and is highly conserved in mammal evolution. Regaining recovery in myocardial jeopardy by inducing principles linking cardiovascular therapy and clinical outcome has been the dream of scientists for decades. Concepts involving embryonic pathways to regenerate adult failing hearts became popular in the early millennium. Since then, abundant data on stem cell research have been published, never reaching widespread application in heart failure therapy. Another conceptual access, using mechanotransduction in cardiac veins to limit myocardial decay, is pressure-controlled intermittent coronary sinus occlusion (PICSO). Recently, we reported acute molecular signs and signals of PICSO activating regulatory miRNA and inducing cell proliferation mimicking cardiac development in adult failing hearts. According to a previously formulated hypothesis, 'embryonic recall', this study aimed to define molecular signals involved in endogenous heart repair during PICSO and study their relation to patient survival. We previously reported a study on the acute molecular effects of PICSO in an observational non-randomized study. Eight out of the thirty-two patients with advanced heart failure undergoing cardiac resynchronization therapy (CRT) were treated with PICSO. Survival was monitored over 10years, and coronary sinus blood samples were collected during intervention before and after 20min and tested for miRNA signalling and proliferation when co-cultured with cardiomyocytes. A numerically lower death rate post-CRT and PICSO as compared with control CRT only, and a non-significant reduction in all-cause mortality risk of 42% was observed (37.5% vs. 54.0%, relative risk=0.58, 95% confidence interval: 0.17-2.05; P=0.402). Four miRNAs involved in cell cycle, proliferation, morphogenesis, embryonic development, and apoptosis significantly increased concomitantly in survivors and PICSO compared with a decrease in non-survivors (hsa-miR Let7b, P<0.01; hsa-miR- 421, P<0.006; hsa-miR 363-3p, P<0.03 and hsa-miR 19b-3p P<0.01). In contrast, three miRNAs involved in proliferation and survival, determining cell fate, and recycling endosomes decreased in survivors and PICSO (hsa miR 101-3p, P<0.03; hsa-miR 25-3p, P<002; hsa-miR 30d-5p P<0.04). In vitro cellular proliferation increased in survivors and lowered in non-survivors showing a pattern distinction, discriminating longevity according to up to 10-year survival in heart failure patients. This study proposes that generating regenerative signals observed during PICSO intervention relate to patient outcomes. Morphogenetic pathways induced by periods of flow reversal in cardiac veins in a domino-like pattern transform embryonic into regenerative signals. Studies supporting the conversion of mechanochemical signals into regenerative molecules during PICSO are warranted to substantiate predictive power on patient longevity, opening new therapeutic avenues in otherwise untreatable heart failure.

Cost-effectiveness analysis of pressure-controlled intermittent coronary sinus occlusion in elective percutaneous coronary intervention

ABSTRACT Objectives Percutaneous coronary intervention (PCI) represents the standard treatment for ST-elevated myocardial infarction, nevertheless, mortality and heart failures are frequent. Pressure-controlled intermittent coronary sinus occlusion (PiCSO) might reduce infarct size showing better patients’ outcomes. We evaluated the cost-effectiveness of PCI+PiCSO compared to PCI from the National Healthcare Service (NHS) perspective in Italy. Methods A Markov model was developed to estimate life years (LYs), quality-adjusted life years (QALYs) and costs. A micro-costing analysis has been performed to inform the cost of PCI+PiCSO procedure. Sensitivity analyses were performed to test the robustness of the model results. Results Considering a willingness-to-pay threshold of 50,000€/QALY for the ICUR and a cost for PCI+PiCSO procedure of 14,654€, the innovative strategy may be cost-effective compared to PCI alone from the Italian NHS perspective, showing an ICUR of 17,530€/QALY (ICER 14,631€/LY) over a lifetime horizon; the probabilistic sensitivity analysis showed that PCI+PiCSO is cost-effective in 78.8% of simulations.Considering the above mentioned willingness-to-pay threshold, PCI+PiCSO strategy would be cost-effective over a lifetime horizon considering a cost for PCI+PiCSO procedure lower than 28,160€. Conclusion PCI+PiCSO procedure may be considered a cost-effective technology that allows reducing cardiac events, while improving patients’ life expectancy and quality of life.

Pressure-controlled intermittent coronary sinus occlusion improves the vasodilatory microvascular capacity and reduces myocardial injury in patients with STEMI.

Preliminary data suggest that pressure-controlled intermittent coronary sinus occlusion (PICSO) might reduce the infarct size (IS) in patients with anterior ST-elevation myocardial infarction (STEMI). However, the applicability of this therapy to patients with inferior STEMI and its exact mechanism of action is uncertain. Thirty-six patients (27 anterior and 9 inferior) with STEMI underwent PICSO-assisted-primary percutaneous intervention (PPCI) and were compared with matched controls who underwent standard PCI (n=72). Median age was 63 (55-70) years and 82% were male. Coronary microvascular status was assessed using thermodilution-derived index of microcirculatory resistance (IMR) and the vasodilatory capacity was assessed using the resistive reserve ratio (RRR). IS and microvascular obstruction (MVO) were assessed using cardiovascular magnetic resonance imaging (CMR) within 48 h and 6months of follow-up. At completion of PPCI, IMR improved significantly in PICSO-treated patients compared with controls in patients with either anterior (63.7 [49.8-74.6] vs. 35.9 [27.9-47.6], p < 0.001) or inferior STEMI (60.0 [47.6-67.1] vs. 22.7 [18.4-35.0], p < 0.001). RRR significantly improved after PICSO treatment for anterior (1.21 [1.01-1.42] vs. 1.73 [1.51-2.16], p=0.002) or inferior STEMI (1.39 [1.05-1.90] vs. 2.87 [2.17-3.78], p=0.001), whereas it did not change in controls compared with baseline. Patients treated with PICSO presented significantly less frequently with MVO (66.6% vs. 86.1%, p=0.024) and smaller 6-month IS compared with controls (26% [17%-30%] vs. 30% [21%-37%], p=0.045). PICSO therapy may improve microvascular function and vasodilatory capacity, which contributes to reducing IS in patients with STEMI undergoing PPCI.

Effect of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) on infarct size in anterior STEMI: PiCSO in ACS study

BackgroundThe aim of this clinical research was to investigate the effects of Pressure-controlled intermittent Coronary Sinus Occlusion (PiCSO) on infarct size at 5 days after primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI). Methods and resultsThis comparative study was carried out in four UK hospitals. Forty-five patients with anterior STEMI presenting within 12 h of symptom onset received pPCI plus PiCSO (initiated after reperfusion; n = 45) and were compared with a propensity score-matched control cohort from INFUSE-AMI (n = 80). Infarct size (% of LV mass, median [interquartile range]) measured by cardiac magnetic resonance (CMR) at day 5 was significantly lower in the PiCSO group (14.3% [95% CI 9.2–19.4%] vs. 21.2% [95% CI 18.0–24.4%]; p = 0.023). There were no major adverse cardiac events (MACE) related to the PiCSO intervention. ConclusionsPiCSO, as an adjunct to pPCI, was associated with a lower infarct size at 5 days after anterior STEMI in a propensity score-matched population.

Acute molecular effects of pressure-controlled intermittent coronary sinus occlusion in patients with advanced heart failure.

AimsCardiac repair has steered clinical attention and remains an unmet need, because available regenerative therapies lack robust mechanistic evidence. Pressure‐controlled intermittent coronary sinus occlusion (PICSO), known to induce angiogenetic and vasoactive molecules as well as to reduce regional ischemia, may activate endogenous regenerative processes in failing myocardium. We aimed to investigate the effects of PICSO in patients with advanced heart failure undergoing cardiac resynchronization therapy.Methods and resultsEight out of 32 patients were treated with PICSO, and the remainder served as controls. After electrode testing including left ventricular leads, PICSO was performed for 20 min. To test immediate molecular responses, in both patient groups, coronary venous blood samples were taken at baseline and after 20 min, the time required for the intervention. Sera were tested for microRNAs and growth factors. To test the ability of up‐regulated soluble factors on cell proliferation and expression of transcription factors [e.g. Krüppel‐like factor 4 (KLF‐4)], sera were co‐cultured with human cardiomyocytes and fibroblasts. As compared with controls, significant differential expression (differences between pre‐values and post‐values in relation to both patient cohorts) of microRNA patterns associated with cardiac development was observed with PICSO. Importantly, miR‐143 (P < 0.048) and miR‐145 (P < 0,047) increased, both targeting a network of transcription factors (including KLF‐4) that promote differentiation and repress proliferation of vascular smooth muscle cells. Additionally, an increase of miR‐19b (P < 0.019) known to alleviate endothelial cell apoptosis was found, whereas disadvantageous miR‐320b (P < 0.023) suspect to impair expression of c‐myc, normally provoking cell cycle re‐entry in post‐mitotic myocytes and miR‐25 (P < 0.023), decreased, a target of anti‐miR application to improve contractility in the failing heart. Co‐cultured post‐PICSO sera significantly increased cellular proliferation both in fibroblasts (P < 0.001) and adult cardiomycytes (P < 0.004) sampled from a transplant recipient as compared with controls. Adult cardiomyocytes showed a seven‐fold increase of the transcription factor KLF‐4 protein when co‐cultured with treated sera as compared with controls.ConclusionsHere, we show for the first time that PICSO, a trans‐coronary sinus catheter intervention, is associated with an increase in morphogens secreted into cardiac veins, normally present during cardiac development, and a significant induction of cell proliferation. Present findings support the notion that epigenetic modifications, that is, haemodynamic stimuli on venous vascular cells, may reverse myocardial deterioration. Further investigations are needed to decipher the maze of complex interacting molecular pathways in failing myocardium and the potential role of PICSO to reinitiate developmental processes to prevent further myocardial decay eventually reaching clinical significance.

Index of microcirculatory resistance-guided therapy with pressure-controlled intermittent coronary sinus occlusion improves coronary microvascular function and reduces infarct size in patients with ST-elevation myocardial infarction: the Oxford Acute Myocardial Infarction - Pressure-controlled Intermittent Coronary Sinus Occlusion study (OxAMI-PICSO study).

The Oxford Acute Myocardial Infarction PICSO (OxAMI-PICSO) study aimed to assess the efficacy of index of microcirculatory resistance (IMR)-guided therapy with pressure-controlled intermittent coronary sinus occlusion (PICSO) in anterior ST-elevation myocardial infarction (STEMI). Patients with anterior STEMI treated with primary percutaneous coronary intervention (pPCI) were enrolled. Pre-stenting IMR was measured and PICSO treatment delivered if pre-stenting IMR was >40. No PICSO treatment was considered in patients with a pre-stenting IMR ≤40. The control group was derived from a historical cohort of STEMI patients with pre-stenting IMR >40 enrolled in the observational OxAMI study. IMR was measured after completion of pPCI in all patients and within 48 hours in PICSO patients and controls. Cardiac magnetic resonance imaging was performed per protocol for infarct size (IS) assessment within 48 hours after pPCI and at six months. A total of 105 patients were enrolled (25 PICSO, 50 controls with pre-stenting IMR >40, 30 with pre-stenting IMR ≤40). Compared to controls, patients treated with PICSO had a lower IMR at 24-48 hours (24.8 [18.5-35.9] vs. 45.0 [32.0-51.3], p<0.001) and lower IS at six months (26.0% [20.2-30.0] vs. 33.0% [28.0-37.0], p=0.006). An IMR-guided treatment with PICSO in anterior STEMI is feasible and may be associated with reduced IS and improved microvascular function.

TCT-123 Pressure-Controlled Intermittent Coronary Sinus Occlusion Reduces Infarct Size After primary PCI: A propensity-controlled matched study

TCT-123 Pressure-Controlled Intermittent Coronary Sinus Occlusion Reduces Infarct Size After primary PCI: A propensity-controlled matched study

TCT-164 Pressure-Controlled Intermittent Coronary Sinus Occlusion Reduces Infarct Size and Results in Functional Recovery After STEMI; Interim analysis of an ongoing trial

TCT-164 Pressure-Controlled Intermittent Coronary Sinus Occlusion Reduces Infarct Size and Results in Functional Recovery After STEMI; Interim analysis of an ongoing trial

TCT-9 Early PICSO preserves LVEF in porcine acute myocardial infarction

A major determinant of mortality and morbidity is the extent of myocardial necrosis after STEMI, and strategies to limit infarct size may therefore improve prognosis. As recently demonstrated in human studies, pressure-controlled intermittent coronary sinus occlusion (PICSO) may enhance myocardial

PICSO: from myocardial salvage to tissue regeneration.

Despite advances in primary percutaneous interventions (PPCI), management of microvascular obstructions in reperfused myocardial tissue remains challenging and is a high-risk procedure. This has led to renewed interest in the coronary venous system as an alternative route of access to the myocardium. This article reviews historical data describing therapeutic options via cardiac veins as well as discussing the clinical potential and limitations of a catheter intervention: pressure controlled intermittent coronary sinus occlusion (PICSO). Collected experimental and clinical information suggest that PICSO also offers the potential for tissue regeneration beyond myocardial salvage. A meta-analysis of observer controlled pICSO application in animal studies showed a dose dependent reduction in infarct size of 29.3% (p < 0.001). Additionally, a 4-fold increase of hemeoxygenase-1 gene expression (p < 0.001) in the center of infarction and a 2.5 fold increase of vascular endothelial growth factor (VEGF) (p < 0.002) in border zones suggest that molecular pathways are initiating structural maintenance. Early clinical evidence confirmed significant salvage and event free survival in patients with acute myocardial infarction and risk reduction for event free survival 5 years after the acute event (p < 0.0001). This experimental and clinical evidence was recently corroborated using modern PICSO technology in PPCI showing a significant reduction of infarct size, when compared to matched controls (p < 0.04). PICSO enhances redistribution of flow towards deprived zones, clearing microvascular obstruction and leading to myocardial protection. Beyond salvage, augmentation of molecular regenerative networks suggests a second mechanism of PICSO involving the activation of vascular cells in cardiac veins, thus enhancing structural integrity and recovery.

TCT-20 Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO) in Acute ST-segment Elevation Myocardial Infarction: Final Results of the Prepare RAMSES Study

TCT-20 Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO) in Acute ST-segment Elevation Myocardial Infarction: Final Results of the Prepare RAMSES Study

Effect of pressure-controlled intermittent coronary sinus occlusion (PICSO) on myocardial ischaemia and reperfusion in a closed-chest porcine model

To investigate a pressure-controlled intermittent coronary sinus occlusion (PICSO) system in an ischaemia/reperfusion model. We randomly assigned 18 pigs subjected to 60 minutes ischaemia by left anterior descending (LAD) coronary artery balloon occlusion to PICSO (n=12, groups A and B) or to controls (n=6, group C). PICSO started 10 minutes before (group A), or 10 minutes after (group B) reperfusion and was maintained for 180 minutes. A continuous drop of distal LAD pressure was observed in group C. At 180 minutes of reperfusion, LAD diastolic pressure was significantly lower in group C compared to groups A and B (p=0.02). LAD mean pressure was significantly less than the systemic arterial mean pressure in group C (p=0.02), and the diastolic flow slope was flat, compared to groups A and B (p=0.03). IgG and IgM antibody deposition was significantly higher in ischaemic compared to non-ischaemic tissue in group C (p<0.05). Significantly more haemorrhagic lesions were seen in the ischaemic myocardium of group C, compared to groups A and B (p=0.002). The necrotic area differed non-significantly among groups. PICSO was safe and effective in improving coronary perfusion pressure and reducing antibody deposition consistent with reduced microvascular obstruction and ischaemia/reperfusion injury.

Intracoronary Hemodynamic Effects of Pressure‐Controlled Intermittent Coronary Sinus Occlusion (PICSO): Results from the First‐In‐Man Prepare PICSO Study

Myocardial reperfusion is frequently suboptimal after ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI). Using a balloon-tipped catheter positioned in the coronary sinus (CS), pressure-controlled intermittent coronary sinus occlusion (PICSO) results in an intermittent obstruction of coronary venous outflow of the left anterior descending artery (LAD), and may improve myocardial perfusion by augmenting redistribution of blood to the border zone of ischemic myocardium. We sought to document the intracoronary hemodynamic effects of PICSO during PCI. We included 15 patients with stable angina scheduled for PCI of the LAD. Balloon occlusion of the LAD was performed twice, once with and once without PICSO and lasting maximally 3 minutes each, to document the effect of PICSO on CS pressure and LAD wedge pressure. Catheter delivery was successful in all patients. The study protocol could not be conducted in 5 patients due to initial calibration difficulties (n = 3), a pressure wire problem (n = 1), and a vagal response at the start of the procedure (n = 1). In the remaining 10 patients, CS occlusion caused a marked increase in mean CS pressure (4.1 ± 7.3 mmHg vs. 22.0 ± 12.6 mmHg; P < 0.001) and CS pulse pressure (4.3 ± 0.8 mmHg vs. 36.1 ± 6.3 mmHg; P < 0.001). Concomitantly, mean distal LAD wedge pressure and wedge pulse pressure increased (32.4 ± 12.2 mmHg vs. 35.5 ± 12.6 mmHg; P < 0.001 and 39.1 ± 27.2 mmHg vs. 45.9 ± 26.0 mmHg; P < 0.001, respectively). At 30 day follow-up, no device-related events occurred. PICSO safely augments CS pressure, thereby increasing LAD coronary wedge pressure. These findings support further evaluation of PICSO in the setting of STEMI.

TCT-399: Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO®): Results From the First-In-Man Prepare PICSO® Pilot Study

TCT-399: Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO®): Results From the First-In-Man Prepare PICSO® Pilot Study

Cardioprotected Percutaneous Coronary Intervention – A Case Study in a Stable Angina Patient

Fast and effective opening of epicardial arteries by thrombolysis or percutaneous coronary intervention (PCI) to restore perfusion to the jeopardised myocardium is considered the cornerstone in the treatment of patients with an acute ST-elevation myocardial infarction (STEMI) leading to a reduction in morbidity and mortality. However, despite successful opening of the coronary artery, myocardial reperfusion remains suboptimal (i.e. measured by blush grade) and results in up to 30–40% of the STEMI patients that is associated with a worse clinical outcome. In this case study of a stable angina patient we document for the first time that cardioprotected PCI (cPCI) using Pressure-controlled Intermittent Coronary Sinus Occlusion (PICSO®) has the potential to increase left anterior descending (LAD) wedge pressure and reduce ischaemia as measured by surface electrocardiogram (ECG). The next step in the development of cPCI will be to apply the PICSO technology in STEMI patients.

Is activation of coronary venous cells the key to cardiac regeneration?

Werner Mohl and coauthors present their Viewpoint examining pressure-controlled intermittent coronary sinus occlusion (PICSO). Here they postulate that PICSO should be introduced into the clinic as a valuable technique for activation of venous endothelium to initiate myocardial recovery and induce regeneration.

Beck and back: A paradigm change in coronary sinus interventions—pulsatile stretch on intact coronary venous endothelium

Strategies to recover myocardium in therapeutically unresponsive patients are again under scrutiny, including techniques developed in the pioneering days of cardiothoracic surgery such as retroperfusion via the coronary sinus--the Beck procedure. An underestimated aspect of retroperfusion is the formation of new vessels. This early observation of neoangiogenesis may be an important mechanism in observed benefits. We hypothesized that periodic pressure elevation in coronary veins induces an analogy to shear stress angiogenic pulses by activating venous endothelium. Pulsatile stretch on venous endothelium can be achieved easily by a pressure-controlled intermittent balloon blockade of the coronary sinus outflow. Three hours of myocardial ischemia was induced in 12 pigs. Pressure-controlled intermittent coronary sinus occlusion was applied in 6 animals 15 minutes after occlusion of the left anterior descending coronary artery. Postmortem myocardial specimens were taken, and heme oxygenase-1, vascular endothelial growth factor gene expression, and hypoxia-induced factor activity were measured. As compared with controls, treated animals released an angiogenic pulse by a 4-fold increase of heme oxygenase-1 gene expression in the infarct area (P < .001), together with a 2.5-fold enhanced transcription of vascular endothelial growth factor in the infarct (P < .006), border (P < .002), and remote (P < .02) areas, whereas hypoxia-induced factor activity was similar in both groups. A significant correlation (P < .01) of the achieved coronary sinus pressure elevation and gene expression was found. Mechanotransduction of pulsatile stretch on coronary venous endothelium by pressure-controlled intermittent coronary sinus occlusion induces heme oxygenase-1 and vascular endothelial growth factor gene expression, leaving the ischemic pathway of the hypoxia-induced factor activity unchanged. This cascade of molecular events closes the argument gap to historical reports of the Beck procedure on revascularization and myocardial salvage.

Myocardial Protection Via the Coronary Sinus Long-Term Effects of Intermittent Coronary Sinus Occlusion as an Adjunct to Reperfusion in Acute Myocardial Infarction

Recent reports on facilitated reperfusion therapy re-address interests in coronary sinus interventions (CSI). Patients in whom short time results have been reported earlier were re-evaluated, with the aim of gathering the long-term results of pressure-controlled intermittent coronary sinus occlusion (PICSO) generated in patients with acute myocardial infarction (MI) and revascularization. Thirty-four patients with ST elevated MI, in whom complete revascularization was achieved, underwent primary thrombolysis with or without PICSO. Follow-up data from these patients were collected for at least 48 months. Immediate perioperative differences were observed for time to peak creatine kinase (CK), as well as cumulative CK. In addition, the time until reperfusion was considerably less than for the control group (p=0.014). Long-term data showed significant differences in reinfarction (p=0.015), as well as in major adverse cardiovascular events, between the 2 groups (p<0.0001). These data, because of the wide interval between collection and current analysis, could have inherited historical bias. Nonetheless, they are also uniquely indicating the potential of CSI to induce not only immediate, but also clinically significant long-term, effects as an adjunct to reperfusion therapy. Therefore, CSI should be, once again, on the study agenda and be placed under contemporary and best-available scientific scrutiny.