1-Year Outcomes Following Transfemoral Transseptal Transcatheter Mitral Valve Replacement: The HighLife TSMVR Feasibility Study.

BACKGROUND: A significant number of patients with severe mitral regurgitation (MR) are not suitable for either surgical or transcatheter edge-to-edge repair because of high surgical risk or inappropriate mitral valve anatomy. OBJECTIVES: The aim of this study was to evaluate the HighLife Trans-Septal Mitral Valve Replacement (TSMVR) system in patients with symptomatic MR and high surgical risk. METHODS: This prospective, multicenter, nonrandomized feasibility study evaluated the safety and performance of the HighLife TSMVR system in patients with moderate to severe or severe symptomatic MR during 1-year follow-up. Echocardiographic data were assessed at an independent core laboratory. RESULTS: A total of 30 patients (mean age 75.6 years, 27% women, median Society of Thoracic Surgeons score 5.5%) with severe MR (90% with secondary MR, median left ventricular ejection fraction 43%) were treated at 13 sites. In 27 of the 30 patients, the HighLife TSMVR system was implanted successfully (technical success rate 90%). Device success at 30 days was 83%. After 1 year, 5 patients (17%) had died. None of the patients who underwent implantation required mitral valve reintervention. All patients who underwent implantation had no or trace (78%) or mild (22%) MR, the mean gradient of the HighLife valve was 5.1 mm Hg, and there were no signs of left ventricular outflow tract obstruction (mean gradient 2.0 mm Hg). CONCLUSIONS: The 1-year results from the HighLife TSMVR feasibility study demonstrate a high technical success rate, excellent valve function, no left ventricular outflow tract obstruction, and no need for mitral valve reintervention. Additional patient outcomes and longer follow-up are needed to confirm these findings. (Expanded Study of the HighLife 28mm Trans-Septal Trans-Catheter Mitral Valve in Patients With Moderate-Severe or Severe Mitral Regurgitation and at High Surgical Risk; NCT04029363).

Endovascular Baroreflex Amplification With the MobiusHD Device in Patients With Heart Failure and Reduced Ejection Fraction: Interim Analysis of the First-in-Human Results.

Background: Endovascular baroreflex amplification with the MobiusHD, a self-expanding stent-like device that is implanted in the internal carotid artery, was designed to reduce the sympathetic overactivity that contributes to progressive heart failure with reduced ejection fraction. Methods: Symptomatic patients (New York Heart Association class III) with heart failure with reduced ejection fraction (left ventricular ejection fraction [LVEF] ≤40%) despite guideline directed medical therapy and n-terminal pro-B type natriuretic peptide (NT-proBNP) levels ≥400 pg/mL in whom carotid ultrasound and computed tomographic angiography demonstrated absence of carotid plaque were enrolled. Baseline and follow-up measures included 6-minute walk distance (6MWD), Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ OSS), and repeat biomarkers and transthoracic echocardiography. Results: Twenty-nine patients underwent device implantation. The mean age was 60.6 ± 11.4 years, and all had New York Heart Association class III symptoms. Mean KCCQ OSS was 41.4 ± 12.7, mean 6MWD was 216.0 ± 43.7 m, median NT-proBNP was 1005.9 pg/mL (894, 1294), and mean LVEF was 34.7 ± 2.9%. All device implantations were successful. Two patients died (161 days and 195 days) and one stroke occurred (170 days) during follow-up. For the 17 patients with 12-month follow-up, mean KCCQ OSS improved by 17.4 ± 9.1 points, mean 6MWD increased by 97.6 ± 51.1 meters, a mean 28.4% reduction from the baseline NT-proBNP concentration was found, and mean LVEF improved by 5.6% ± 2.9 (paired data). Conclusion: Endovascular baroreflex amplification with the MobiusHD device was safe and effected positive changes in quality of life, exercise capacity, and LVEF, consistent with observed reductions in NT-proBNP levels.

Percutaneous haemodynamic and renal support in patients presenting with decompensated heart failure: A multi-centre efficacy study using the Reitan Catheter Pump (RCP).

BACKGROUND: Worsening heart failure complicated by congestion, hypotension, and renal dysfunction is difficult to manage, increasingly common and predicts a poor outcome. Novel therapies are required to facilitate diuresis and implementation of disease-modifying interventions in preparation for hospital discharge. Accordingly, we investigated the haemodynamic and renal effects of the Reitan Catheter Pump (RCP) percutaneous support device in patients admitted with decompensated heart failure (DHF). METHODS: This was a prospective observational study of 20 patients admitted with DHF, ejection fraction < 30%, and Cardiac index (CI) < 2.1 L/min/m2 in need of inotropic/mechanical support. RESULTS: Patients underwent RCP support for a mean of 18.3 (±6.3) hours. The RCP increased CI from 1.84 L/min/m2 (±0.27), to 2.41 L/min/m2 (±0.45, p = 0.04), increased urine output (71 mL/h (±65) to 227 ml/h (±179) (p = 0.006) with a concomitant reduction in serum creatinine (188 µmol/L (±87) to 161 µmol/L (±78) (p = 0.0007). There were no clinically significant haemolysis, vascular injury, or thrombo-embolic complications. CONCLUSIONS: For patients admitted with DHF, the RCP improves cardiac index, diuresis and renal function without causing important complications.

Optimization of Axial Pump Characteristic Dimensions and Induced Hemolysis for Mechanical Circulatory Support Devices.

The application of axial pumps as ventricular assist devices (VADs) requires significant modifications to the size and characteristics of industrial pumps due to the difference in flow fields of industrial and medical pumps. Industrial pumps operate in the region of Reynolds number Re = 10, whereas axial blood pumps operate in Re < 10. The common pump design technique is to rely on the performance of previously designed pumps using the concept of fluid dynamic similarity. Such data are available for industrial pumps as specific speed-specific diameter (ns-ds) graphs. The difference between the flow fields of industrial and medical pumps makes the industrial ns-ds graphs unsuitable for medical pumps and consequently several clinically available axial blood pumps operate with low efficiencies. In this article, numerical and experimental techniques were used to design 62 axial pump impellers with different design characteristics suitable for VADs and mechanical circulatory support devices (MCSDs). The impellers were manufactured and experimentally tested in various operating conditions of flow, pressure, and rotational speed. The hemocompatibility of the impellers was numerically investigated by modeling shear stress and hemolysis. The highest efficiency of each pump impeller was plotted on an ns-ds diagram. The nondimensional results presented in this article enable preliminary design of efficient and hemocompatible axial flow pumps for VADs and MCSDs.

Computational Parametric Study of the Axial and Radial Clearances in a Centrifugal Rotary Blood Pump.

In centrifugal rotary blood pumps (RBP), clearances are a critical parameter in determining blood trauma. This study investigates the effect of axial clearance (Cax) and radial clearance (Crad) on the hydrodynamic and hemolytic performance of a centrifugal RBP. A centrifugal pump was parameterized so that it could be defined by geometric variables Cax and Crad. Optimal Latin hypercube sampling was used to determine design points based on Cax, Crad, and rotor speed (ω). For each design point, a computational simulation was conducted to determine efficiency (η) and normalized index of hemolysis (NIH). Next, a response surface (RS) was created to estimate these performance parameters based on the design variables. The results show that for a given Cax, when Crad is decreased, η increases until Crad = 0.15 mm, beyond which η deceases. For a given Crad, Cax has a unimodal relationship with η. The NIH has a unimodal relationship with both Cax and Crad. The mechanisms behind these relationships were investigated by various analytical methods. It was found that vortices in the secondary flow paths were a critical factor in determining efficiency and hemolysis. The optimal clearance values discerned in this study are only valid for the specific impeller geometry and operating conditions analyzed.

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

BACKGROUND: Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. METHODS: SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. FINDINGS: Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. INTERPRETATION: Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. FUNDING: Medtronic.

The Effect of Geometry on the Efficiency and Hemolysis of Centrifugal Implantable Blood Pumps.

The application of centrifugal pumps as heart assist devices imposes design limitations on the impeller geometry. Geometry and operating parameters will affect the performance and the hemocompatibility of the device. Among all the parameters affecting the hemocompatibility, pressure, rotational speed, blade numbers, angle, and width have significant impact on the blood trauma. These parameters directly (pressure, speed) and indirectly (geometry) affect the efficiency of the pump as well. This study describes the experimental investigation on geometric parameters and their effect on the performance of small centrifugal pumps suitable for Mechanical Circulatory Support (MCS) devices. Experimental and numerical techniques were implemented to analyze the performance of 15 centrifugal impellers with different characteristics. The effect of each parameter on the pump performance and hemolysis was studied by calculating the normalized index of hemolysis (NIH) and the shear stress induced in each pump. The results show five and six blades, 15-35° outlet angle, and the lowest outlet width that meets the required pressure rise are optimum values for an efficient hemocompatible pump.

An exploratory randomized control study of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with ischaemic cardiomyopathy: the REGENERATE-IHD clinical trial.

AIMS: The effect of combined cytokine and cell therapy in ischaemic cardiomyopathy is unknown. Meta-analyses suggest improved cardiac function with cell therapy. The optimal cell delivery route remains unclear. We investigated whether granulocyte colony-stimulating factor (G-CSF) alone or in combination with intracoronary (i.c.) or intramyocardial (i.m.) injection of autologous bone marrow-derived cells (BMCs) improves cardiac function. METHODS AND RESULTS: Ninety patients with symptomatic ischaemic cardiomyopathy and no further treatment options were enrolled in the randomized, placebo-controlled, single-centre REGENERATE-IHD study. Randomization was to one of three arms: peripheral, i.c., or i.m. In each arm, patients were randomized to active treatment or placebo. All patients, apart from the peripheral placebo group (saline only) received G-CSF for 5 days. The i.c. and i.m. arms received either BMCs or serum (placebo). The primary endpoint was change in LVEF at 1 year assessed by cardiac magnetic resonance imaging/computed tomography. The i.m. BMC group showed a significant improvement in LVEF of 4.99% (95% confidence interval 0.33-9.6%; P = 0.038) at 1 year. This group also showed a reduction in NYHA class at 1 year and NT-proBNP at 6 months. No other group showed a significant change in LVEF. This finding is supported by post-hoc between-group comparisons. CONCLUSION: We have shown that G-CSF combined with autologous i.m. BMCs has a beneficial effect on cardiac function and symptoms. However, this result should be considered preliminary in support of a clinical benefit of i.m. stem cell infusion in 'no option' patients and needs further exploration in a larger study.

Cocoa flavanols reduce N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure.

AIMS: Poor prognosis in chronic heart failure (HF) is linked to endothelial dysfunction for which there is no specific treatment currently available. Previous studies have shown reproducible improvements in endothelial function with cocoa flavanols, but the clinical benefit of this effect in chronic HF has yet to be determined. Therefore, the aim of this study was to assess the potential therapeutic value of a high dose of cocoa flavanols in patients with chronic HF, by using reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an index of improved cardiac function. METHODS AND RESULTS: Thirty-two patients with chronic HF, stable on guideline-directed medical therapy, were randomized to consume 50 g/day of high-flavanol dark chocolate (HFDC; 1064 mg of flavanols/day) or low-flavanol dark chocolate (LFDC; 88 mg of flavanols/day) for 4 weeks and then crossed over to consume the alternative dark chocolate for a further 4 weeks. Twenty-four patients completed the study. After 4 weeks of HFDC, NT-proBNP (mean decrease % ± standard deviation) was significantly reduced compared with baseline (-44 ± 69%), LFDC (-33 ± 72%), and follow-up (-41 ± 77%) values. HFDC also reduced diastolic blood pressure compared with values after LFDC (-6.7 ± 10.1 mmHg). CONCLUSIONS: Reductions in blood pressure and NT-proBNP after HFDC indicate decreased vascular resistance resulting in reduced left ventricular afterload. These effects warrant further investigation in patients with chronic HF.

Optimization of Centrifugal Pump Characteristic Dimensions for Mechanical Circulatory Support Devices.

The application of artificial mechanical pumps as heart assist devices impose power and size limitations on the pumping mechanism, and therefore requires careful optimization of pump characteristics. Typically new pumps are designed by relying on the performance of other previously designed pumps of known performance using concepts of fluid dynamic similarity. Such data are readily available for industrial pumps, which operate in Reynolds numbers region of 10. Heart assist pumps operate in Reynolds numbers of 10. There are few data available for the design of centrifugal pumps in this characteristic range. This article develops specific speed versus specific diameter graphs suitable for the design and optimization of these smaller centrifugal pumps concentrating in dimensions suitable for ventricular assist devices (VADs) and mechanical circulatory support (MCS) devices. A combination of experimental and numerical techniques was used to measure and analyze the performance of 100 optimized pumps designed for this application. The data are presented in the traditional Cordier diagram of nondimensional specific speed versus specific diameter. Using these data, nine efficient designs were selected to be manufactured and tested in different operating conditions of flow, pressure, and rotational speed. The nondimensional results presented in this article enable preliminary design of centrifugal pumps for VADs and MCS devices.

In-vitro investigation of cerebral-perfusion effects of a rotary blood pump installed in the descending aorta.

This study describes use of a cardiovascular simulator to replicate the hemodynamic responses of the cerebrovascular system with a mechanical circulatory support device operating in the descending aorta. To do so, a cerebral autoregulation unit was developed which replicates the dilation and constriction of the native cerebrovascular resistance system and thereby regulates the cerebral flow rate within defined limits. The efficacy of the replicated autoregulation mechanism was investigated by introducing a number of step alterations in mean aortic pressure and monitoring the cerebral flow. The steady responses of the cerebral flow to changes in mean aortic pressure were in good agreement with clinical data. Next, a rotary pump, modeling a mechanical circulatory support device, was installed in the descending aorta and the hemodynamic responses of the cerebral system were investigated over a wide range of pump operating conditions. Insertion of a mechanical circulatory support device in the descending aorta presented an improved cardiac output as a result of afterload reduction. It was observed that the primary drop in cerebral flow, caused by the pump in the descending aorta, was compensated over the course of five seconds due to a gradual decrease in cerebrovascular resistance. The experimental results suggest that the implantation of a mechanical circulatory support device in the descending aorta, a less invasive procedure than typical mechanical circulatory support implantation, will not have an adverse effect on the cognitive function, provided that the cerebral autoregulation is largely unimpaired.

Radial primary percutaneous coronary intervention is independently associated with decreased long-term mortality in high-risk ST-elevation myocardial infarction patients.

AIM: To compare long-term clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PPCI) using radial and femoral arterial access. METHODS AND RESULTS: The present study was an observational cohort study of patients with STEMI treated consecutively with PPCI between 2004 and 2011 at a single centre. The primary end point was all-cause mortality at a median follow-up of 3 years.Among 2727 patients, 1600 (58.7%) underwent PPCI via the femoral route. The femoral group was older (64.7 vs. 61.7 years; P < 0.0001), and had higher rates of diabetes (18.6% vs. 16.0%; P < 0.0001), previous PCI (11.2 vs. 7.8%; P = 0.004), previous myocardial infarction (15.3 vs. 8.3%; P < 0.0001) and cardiogenic shock (9.8 vs. 1.3%; P < 0.0001). Bleeding complications were more frequent in the femoral group (4.7 vs. 1.2%; P < 0.0001). The 5-year death rate was significantly higher in the femoral group than in the radial group (10.4 vs. 3.0%; P < 0.0001). After adjustment for confounding variables, bleeding complications [heart rate 2.07 (95% confidence interval 1.05-4.08)] and femoral access [heart rate 1.60 (95% confidence interval 1.02-2.53)] were independent predictors of all-cause mortality. After stratification using the propensity score, excess long-term mortality in patients treated via the femoral approach was predominantly in patients with a high baseline risk of death. CONCLUSION: Patients undergoing PPCI via the femoral route are at a higher risk of adverse short-term and long-term outcomes than patients undergoing PPCI via the radial route. Patients with a high baseline risk may benefit most from radial access, and future outcome studies should focus on the most at-risk patients.

Safety and feasibility of intramyocardial versus intracoronary delivery of autologous cell therapy in advanced heart failure: the REGENERATE-IHD pilot study.

AIM: This study presents an interim safety and feasibility analysis of the REGENERATE-IHD randomized controlled trial, which is examining the safety and efficacy of three different delivery routes of bone marrow-derived stem cells (BMSCs) in patients with ischemic heart failure. METHODS & RESULTS: The first 58 patients recruited to the REGENERATE-IHD study are included in this interim analysis (pilot). Symptomatic patients with ischemic heart failure were randomized to receive subcutaneous granulocyte colony-stimulating factor or saline injections only; or subcutaneous granulocyte colony-stimulating factor injections followed by intracoronary or intramyocardial injections of BMSCs or serum (control). No significant differences were found in terms of safety and feasibility between the different delivery routes, with no significant difference in procedural complications or major adverse cardiac events. There was a signal towards improved heart failure symptoms in the patients treated with intramyocardial injection of mobilized BMSCs. CONCLUSION: Peripheral mobilization of BMSCs with or without subsequent direct myocardial delivery appears safe and feasible in patients with chronic ischemic heart failure.

In vitro comparison of two different mechanical circulatory support devices installed in series and in parallel.

This study investigates the novel approach of placing a ventricular assist pump in the descending aorta in series configuration with the heart and compares it with the two traditional approaches of left-ventricle-to-ascending-aorta (LV-AA) and left-ventricle-to-descending-aorta (LV-DA) placement in parallel with the heart. Experiments were conducted by using the in-house simulator of the cardiovascular blood-flow loop (SCVL). The results indicate that the use of the LV-AA in-parallel configuration leads to a significant improvement in the systemic and pulmonic flow as the level of continuous flow is increased; however, this approach is considered highly invasive. The use of the LV-DA in-parallel configuration leads to an improvement in the systemic and pulmonic flow at lower levels of continuous flow but at higher levels of pump support leads to retrograde flow. In both in-parallel configurations, increasing the level of pump continuous flow leads to a decrease in pulsatility to a certain extent. The results of placing the pump in the descending aorta in series configuration show that the pressure drop upstream of the pump facilitates cardiac output as a result of afterload reduction. In addition, the pressure rise downstream of the pump may assist with renal perfusion. However, at the same time, the pressure drop generated at the proximal part of the descending aorta induces a slight drop in carotid perfusion, which would be autoregulated by the brain in a native cardiovascular system. The pulse wave analysis shows that placing the pump in the descending aorta leads to improved pulsatility in comparison with the traditional in-parallel configurations.

A randomised double-blind control study of early intracoronary autologous bone marrow cell infusion in acute myocardial infarction (REGENERATE-AMI).

INTRODUCTION: Acute myocardial infarction (AMI) remains a major cause of mortality and morbidity worldwide despite the latest therapeutic advances designed to decrease myocardial injury. Preclinical and emerging clinical evidence show that the intracoronary injection of autologous bone marrow mononuclear cells (BMCs) following AMI leads to improvement in left ventricular ejection function (LVEF). In this clinical trial we will for the first time assess the effect of early (<24 h) infusion of autologous BMCs following AMI on cardiac function. METHODS AND ANALYSIS: REGENERATE-AMI is a double-blind, randomised, multicentre, placebo-controlled trial to determine whether early (<24 h) intracoronary infusion of BMCs improves LVEF after AMI. The study will enrol 100 patients presenting with an anterior AMI demonstrating anterior regional wall motion abnormality. Patients will be randomised to receive intracoronary infusion of BMCs or placebo (0.9% saline). Primary endpoint will be change in LVEF at 1 year compared to baseline, measured by cardiac MRI. Secondary endpoints at 6 months include the change in global LVEF relative to baseline measured by quantitative left ventriculography and echocardiography, as well as major adverse cardiac events which is also measured at 1 year. ETHICS AND DISSEMINATION: The study will be performed in agreement with the Declaration of Helsinki and is approved by local ethics committee (NRES Committee London West London: 07/Q0603/76). TRIAL REGISTRATION: http://clincialtrials.gov (NCT00765453). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals.

Lack of association between dual antiplatelet therapy use and stent thrombosis between 1 and 12 months following resolute zotarolimus-eluting stent implantation.

AIM: The optimal duration of dual antiplatelet therapy (DAPT) following the use of new generation drug-eluting stents is unknown. METHODS AND RESULTS: The association between DAPT interruption and the rates of stent thrombosis (ST) and cardiac death/target-vessel myocardial infarction (CD/TVMI) in patients receiving a Resolute zotarolimus-eluting stent (R-ZES) was analysed in 4896 patients from the pooled RESOLUTE clinical programme. Daily acetylsalicylate (ASA) and a thienopyridine for 6-12 months were prescribed. A DAPT interruption was defined as any interruption of ASA and/or a thienopyridine of >1 day; long interruptions were >14 days. Three groups were analysed: no interruption, interruption during the first month, and >1-12 months. There were 1069 (21.83%) patients with a DAPT interruption and 3827 patients with no interruption. Among the 166 patients in the 1-month interruption group, 6 definite/probable ST events occurred (3.61%; all long DAPT interruptions), and among the 903 patients in the >1-12 months (60% occurred between 6 and 12 months) interruption group, 1 ST event occurred (0.11%; 2-day DAPT interruption). Among patients with no DAPT interruption, 32 ST events occurred (0.84%). Rates of CD/TVMI were 6.84% in the 1-month long interruption group, 1.41% in the >1-12 months long interruption group, and 4.08% in patients on continuous DAPT. CONCLUSION: In a pooled population of patients receiving an R-ZES, DAPT interruptions within 1 month are associated with a high risk of adverse outcomes. Dual antiplatelet therapy interruptions between 1 and 12 months were associated with low rates of ST and adverse cardiac outcomes. Randomized clinical trials are needed to determine whether early temporary or permanent interruption of DAPT is truly safe. ClinicalTrials.gov Identifiers: NCT00617084; NCT00726453; NCT00752128; NCT00927940.

Prognostic impact of anaemia on patients with ST-elevation myocardial infarction treated by primary PCI.

AIM: The aim of this study was to investigate the effects of baseline anaemia on the outcome in patients treated by primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction. METHODS: This study was a retrospective cohort study of 2418 patients with ST-elevation myocardial infarction treated by PPCI between January 2004 and August 2010 at a single centre. We investigated the outcome in patients with anaemia compared with that in patients with a normal haemoglobin (Hb) level. Anaemia was defined according to the WHO definition as an Hb level less than 12 g/dl for female individuals and less than 13 g/dl for male individuals. We also calculated hazard ratios using a stratified model according to the Hb level. RESULTS: A total of 471 (19%) patients were anaemic at presentation. The anaemic cohort was older (72.2 vs. 62.4 years, P<0.0001) and had a higher incidence of diabetes (28 vs. 16%, P<0.0001), hypertension (57 vs. 43%, P=0.01), hypercholesterolaemia (48 vs. 40%, P=0.007), previous PCI (15 vs. 9%, P<0.0001), previous myocardial infarction (23 vs. 12%, P=0.002), and cardiogenic shock (12 vs. 5%, P<0.0001). Over a mean follow-up period of 3 years there was significantly higher all-cause mortality in the anaemic group compared with the normal Hb group (20.4 vs. 13.5%, P<0.0001). However, after adjustment for all variables using multivariate analysis, anaemia (on the basis of the WHO definitions) was found not to be an independent predictor of mortality or major adverse cardiac events over the follow-up period. Further, when we used a model stratified by g/dl, we found that there was an increased risk for adverse outcomes among men with low Hb levels. There appeared to be a threshold value of Hb (13 g/dl) associated with increased risk. Although a similar trend was observed among women, no significant difference was observed. CONCLUSION: Patients with anaemia undergoing PPCI are at a higher risk of an adverse outcome. Anaemia is a simple and powerful marker of poor prognosis. Although anaemia (based on the WHO definitions) does not appear to be an independent predictor of all-cause mortality or major adverse cardiac events after PPCI on multivariate analysis, there appears to be a threshold value of Hb among men, below which there is an associated increased risk for PPCI.

Contemporary analysis of incidence and outcomes of stent thrombosis presenting as ST elevation myocardial infarction in a primary percutaneous coronary intervention cohort.

There are limited data about the effectiveness of primary percutaneous coronary intervention (PPCI) for stent thrombosis treatment. We aimed to evaluate the prevalence and outcomes of PPCI in patients with ST elevation acute myocardial infarction (STEMI) due to stent thrombosis, and comparing the outcomes with patients treated for de novo coronary thrombosis. This was an observational cohort study of 2,935 patients who underwent PPCI from 2003 to 2011 with follow-up for a median of 3.0 years (interquartile range 1.2 to 4.6). The primary end point was the first major adverse cardiac event (MACE) defined as death, nonfatal myocardial infarction, stroke, or target vessel revascularization. Stent thrombosis overall accounted for 6.6% (194 of 2,935) of all STEMIs with a proportion that increased over time (3.3% in 2004 to 9.4% in 2011). A total of 34.5% were early, 30.9% late stent thrombosis, and 34.5% were very late stent thrombosis. Indications for the original intervention were elective in 27.8%, after acute coronary syndrome (non-STEMI or unstable angina) in 21.1%, and after PPCI in 51.1%. Patients with stent thrombosis had higher rates of hypertension, hypercholesterolemia, diabetes, renal dysfunction, and previous myocardial infarction or coronary artery bypass surgery compared with patients with native artery occlusion. MACE rates were higher in patients with stent thrombosis compared with patients with native artery occlusions (40.9%, 95% confidence interval [CI] 31.1 to 50.6 vs 15.1%, 95% CI 12.5 to 18.3; p <0.0001). The poor outcome of stent thrombosis was particularly associated with early and late stent thromboses. Very late stent thrombosis appears to be a relatively less serious event, with similar outcomes to native vessel thromboses (MACE very late stent thrombosis 16.5%, 95% CI 8.2 to 28.6 vs native 15.1%, 95% CI 12.5 to 18.3, p = 0.245). In conclusion, stent thrombosis accounts for an increasing proportion of STEMI and is associated with worse outcomes compared with native artery occlusion.

In vitro cardiovascular system emulator (bioreactor) for the simulation of normal and diseased conditions with and without mechanical circulatory support.

This article presents a new device designed to simulate in vitro flow rates, pressures, and other parameters representing normal and diseased conditions of the human cardiovascular system. Such devices are sometimes called bioreactors or "mock" simulator of cardiovascular loops (SCVLs) in literature. Most SCVLs simulate the systemic circulation only and have inherent limitations in studying the interaction of left and right sides of circulation. Those SCVLs that include both left and right sides of the circulation utilize header reservoirs simulating cycles with constant atrial pressures. The SCVL described in this article includes models for all four chambers of the heart, and the systemic and pulmonary circulation loops. Each heart chamber is accurately activated by a separate linear motor to simulate the suction and ejection stages, thus capturing important features in the perfusion waveforms. Four mechanical heart valves corresponding to mitral, pulmonary, tricuspid, and aortic are used to control the desired unidirectional flow. This SCVL can emulate different physiological and pathological conditions of the human cardiovascular system by controlling the different parameters of blood circulation through the vascular tree (mainly the resistance, compliance, and elastance of the heart chambers). In this study, four cases were simulated: healthy, congestive heart failure, left ventricular diastolic dysfunction conditions, and left ventricular dysfunction with the addition of a mechanical circulatory support (MCS) device. Hemodynamic parameters including resistance, pressure, and flow have been investigated at aortic sinus, carotid artery, and pulmonary artery, respectively. The addition of an MCS device resulted in a significant reduction in mean blood pressure and re-establishment of cardiac output. In all cases, the experimental results are compared with human physiology and numerical simulations. The results show the capability of the SCVL to replicate various physiological and pathological conditions with and without MCS.