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.

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.

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.

Clinical outcomes after myocardial revascularization according to operator training status: cohort study of 22,697 patients undergoing percutaneous coronary intervention or coronary artery bypass graft surgery.

AIMS: Myocardial revascularization by either coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI) carries the risk of serious complications. Observational data suggest that outcomes may be improved by experienced operators, but there are few studies that have analysed the relationship between mortality and primary operator grade. The aim of this study was to investigate the effect of operator grade (trainee vs. consultant) upon outcomes of revascularization procedures. METHODS AND RESULTS: This was an observational study at a tertiary cardiology centre with accredited training programmes, between 2003 and 2011. A total of 22 697 consecutive patients undergoing either CABG or PCI were included. Associations between operator grade and mortality were assessed by hazard ratios, estimated by Cox regression analyses; 6689 patients underwent CABG, whereas 16 008 underwent PCI. Trainees performed 1968 (29.4%) CABG procedures and 8502 (53.1%) PCI procedures. The proportion of procedures performed by trainees declined over time for both CABG (30.2% in 2003 vs. 26.0% in 2010) and for PCI (58.1% in 2003 vs. 44.5% in 2010). In the unadjusted Cox analysis, consultant operator grade was associated with an increased 5-year mortality after both CABG [HR: 1.26 (95% CI: 1.07-1.47)] and PCI procedures [HR: 1.34 (95% CI: 1.22-1.47)] compared with a trainee operator. However, following multiple adjustment, consultant grade was no longer associated with mortality after either procedure [CABG: HR: 1.02 (95% CI: 0.87-1.20), PCI: HR: 1.08 (95% CI: 0.98-1.20)]. CONCLUSION: There was no observed detrimental effect on patient outcomes arising from procedures undertaken by trainees working in a structured training environment compared with consultants.

Impact of a dedicated "radial lounge" for percutaneous coronary procedures on same-day discharge rates and bed utilization.

BACKGROUND: Two advantages of transradial coronary procedures are an increased potential for same-day discharge and better resource management. This study assessed the impact of a dedicated "radial lounge" (1) on the rate of same-day discharge after elective percutaneous coronary intervention (PCI) and coronary angiography and (2) on bed utilization. METHODS: We compared our unit's rates of same-day discharge in patients who underwent elective PCI or coronary angiography in the year before and in the year after the opening of a dedicated radial lounge for elective patients. RESULTS: In its first year of operation, 439 patients who underwent PCI and 1,109 patients who underwent angiography were managed in the radial lounge. Among these patients, the rate of same-day discharge was 84.7% after PCI and 97.0% after angiography. Requirement for overnight admission was significantly more common after femoral access compared with radial access for both angiography (4.1% vs 2.8%, P < .05) and PCI (20.3% vs 14.2%, P < .01). The unit's overall rate of same-day discharge increased from 2.3% to 51.2% after elective PCI (P < .0005) and from 72.7% to 84.9% after elective angiography (P < .005). An estimated 595 bed days were saved through reduced overnight admissions in elective patients. CONCLUSIONS: Our unit's overall rates of same-day discharge after elective PCI and coronary angiography increased dramatically in the year after the opening of a dedicated radial lounge. This was directly attributable to the high rates of same-day discharge in radial lounge patients. The radial lounge impacted favorably on in-patient bed capacity.

Deployment of drug-eluting stents for isolated proximal lad disease is associated with lower major adverse cardiac events and no increase in stent thrombosis when compared with bare metal stents: a 5-year observational cohort study.

BACKGROUND: Drug-eluting stents (DES) may be associated with an increased risk of late stent thrombosis (ST) compared with bare metal stents (BMS). We compared major adverse cardiac events (MACE) and long term all cause mortality in patients with isolated proximal LAD disease treated with DES or BMS. METHOD AND RESULTS: This study of 1653 patients with isolated proximal LAD disease, includes 643 treated with BMS and 1010 treated with DES. All patients received standard dual antiplatelet treatment. MACE after 5 years were less frequent in DES compared with BMS (12.1% 95% CI 9.3-14.2 versus 21.3% 95% CI: 16.9-25.1, P < 0.0001), driven largely by a decreased rate of both target vessel and lesion revascularization (TVR: 6.3%, 95% CI 4.0-7.5% versus 14.7%, 95% CI 11.0-17.3%, P < 0.0001, TLR: (5.3%, 95% CI 3.2-7.1% versus 13.2%, 95% CI 9.8.0-15.4%, P < 0.0001). There was no difference in the rate of death, myocardial infarction, or CVA. Incidence of stent thrombosis was also comparable (1.2% 95% CI: 0.6-2.6% versus 1.1% 95% CI: 0.6-2.5%, P = 0.8). Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.55 (95% confidence intervals 0.41-0.73) with no difference in the hazard of all cause mortality (HR: 1.04 95% CI: 0.67-1.61). CONCLUSION: When treating proximal LAD disease, use of DES was associated with a lower MACE rate than BMS, with no differences in the incidence of stent thrombosis, myocardial infarction or 5 year all cause mortality. Our data suggests that despite the adverse prognostic correlates of proximal LAD disease, DES deployment in this location is both safe and clinically more effective than BMS.

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.

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).

Outcomes in patients with renal impairment undergoing percutaneous coronary intervention and implantation of the Endeavor zotarolimus-eluting stent: 1- and 2-year data from the E-Five Registry.

OBJECTIVES: Renal impairment (RI) is a predictor of poor outcomes in patients with cardiovascular disease, but its influence in the setting of percutaneous coronary intervention and zotarolimus-eluting stent (ZES) implantation has not been described. This study evaluated the impact of RI on clinical outcomes in patients participating in the E-Five Registry. BACKGROUND: E-Five was a prospective, multicenter, global registry of 8,314 patients; 2,116 patients were followed to 2 years. METHODS: Patients (excluding those who had undergone renal transplantation) were grouped according to renal function (normal function/mild RI, serum creatinine <110 µmol/L; moderate RI, 110-200 µmol/L; severe RI, >200 µmol/L) and their outcomes evaluated retrospectively. Major adverse cardiac events (MACE; i.e., death, myocardial infarction, emergency cardiac bypass surgery, or target lesion revascularization) and stent thrombosis events at 1 and 2 years were compared between groups. RESULTS: The 1-year MACE rate in patients with mild RI was 6.8%, compared with 8.9 and 18.1% in patients with moderate and severe RI (P = 0.002 across groups). At 2 years, death occurred in 16% of those with severe RI, compared with 2.0 and 4.7% in those with mild and moderate RI (P = 0.002). There was no significant difference in the rates of target lesion revascularization or target vessel failure. CONCLUSIONS: Greater severity of RI at intervention is associated with greater mortality and MACE but unchanged revascularization rates after ZES implantation.

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.

Extended follow-up safety and effectiveness of the Endeavor zotarolimus-eluting stent in real-world clinical practice: two-year follow-up from the E-Five Registry.

OBJECTIVES: To present data from the cohort of patients in the all-comers Endeavor zotarolimus-eluting stent (ZES) registry (E-Five) who underwent 2-year follow-up. BACKGROUND: The Endeavor ZES has been shown to be safe and efficacious for treatment of single, de novo lesions in patients with stable coronary artery disease. E-Five evaluated the ZES in over 8,000 real-world patients, at 188 sites followed to 1 year. A subset of sites continued follow-up through 2 years to evaluate late-term safety and effectiveness of the ZES in this population with diverse clinical and lesion characteristics. METHODS: E-Five, a prospective, multicenter, nonrandomized global registry, collected 2-year outcomes for 2,116 patients from 26 centers. Sites were selected for participation based on patient accrual rates and the ability to continue follow-up activities for an additional year. Complete data was available for 2,054 patients. To observe whether or not a sustained benefit was achieved, data for all patients from the selected sites were included in the analysis. RESULTS: The outcomes in the 2-year cohort tracked with the results of randomized controlled trials using the Endeavor ZES. One year results were MACE 7.5%, TLR 4.5%, and ARC definite/probable stent thrombosis 0.6%. Outcomes at 2 years for MACE, TLR, and ARC definite/probable stent thrombosis were 8.5, 5.1, and 0.7%, respectively. CONCLUSIONS: Long-term efficacy and safety outcomes were maintained between 1 and 2 years for the 2-year patient cohort, with only a small number of additional MACE, TLR, and very late stent thrombosis events.

Prevention of thrombus embolization during primary percutaneous intervention using a novel mesh covered stent.

Embolization of athero-thrombotic material during primary percutaneous coronary intervention is a common cause of periprocedural complication. Methods developed to reduce embolization include thrombus aspiration, and distal protection. We report five cases of primary percutaneous intervention to coronary arteries that contain large amounts of thrombus, using a novel mesh covered stent. The mesh covering of the stent is designed such that it is theoretically able to ensnare thrombus and thus prevent distal migration of embolic material. In all cases, TIMI grade III flow was achieved at the end of the procedure, despite the extensive thrombus burden.

A first-in-man study of the Reitan catheter pump for circulatory support in patients undergoing high-risk percutaneous coronary intervention.

OBJECTIVES: To investigate the safety of a novel percutaneous circulatory support device during high-risk percutaneous coronary intervention (PCI). BACKGROUND: The Reitan catheter pump (RCP) consists of a catheter-mounted pump-head with a foldable propeller and surrounding cage. Positioned in the descending aorta the pump creates a pressure gradient, reducing afterload and enhancing organ perfusion. METHODS: Ten consecutive patients requiring circulatory support underwent PCI; mean age 71 +/- 9; LVEF 34% +/- 11%; jeopardy score 8 +/- 2.3. The RCP was inserted via the femoral artery. Hemostasis was achieved using Perclose sutures. PCI was performed via the radial artery. Outcomes included in-hospital death, MI, stroke, and vascular injury. Hemoglobin (Hb), free plasma Hb (fHb), platelets, and creatinine (cre) were measured pre PCI and post RCP removal. RESULTS: The pump was inserted and operated successfully in 9/10 cases (median 79 min). Propeller rotation at 10,444 +/- 1,424 rpm maintained an aortic gradient of 9.8 +/- 2 mm Hg. Although fHb increased, there was no significant hemolysis (4.7 +/- 2.4 mg/dl pre vs. 11.9 +/- 10.5 post, P = 0.04, reference 20 mg/dl). Platelets were unchanged (pre 257 +/- 74 x 10(9) vs. 245 +/- 63, P = NS). Renal function improved (cre pre 110 +/- 27 micromol/l vs. 99 +/- 28, P = 0.004). The RCP was not used in one patient following femoral introducer sheath related aortic dissection. All PCI procedures were successful with no deaths or strokes, one MI, and no vascular complications following pump removal. CONCLUSIONS: The RCP can be used safely in high-risk PCI patients. This device may be an alternative to other percutaneous systems when substantial cardiac support is needed.

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.

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.

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.

Real-world safety and efficacy of the endeavor zotarolimus-eluting stent: early data from the E-Five Registry.

The E-Five is a prospective, nonrandomized, multicenter global registry of patients receiving the Endeavor zotarolimus-eluting stent (ZES; Medtronic Vascular, Santa Rosa, CA) for the treatment of coronary artery stenosis. All consecutive procedures were included in the registry, without any specific anatomic or clinical exclusion criteria. Since October 2005, 8,318 patients have been enrolled in the E-Five Registry at 188 hospitals in Europe, South America, Australia, New Zealand, and Asia, and 10,343 lesions have been treated. The primary end point is the rate of major adverse cardiac events (MACE) at 1 year. Of the lesions treated, 60.3% were American College of Cardiology (ACC) and American Heart Association (AHA) type B2 or C lesions, and 16.5% were bifurcation stenoses. The average lesion length was 18.50 +/- 10.60 mm, and 50.6% of the lesions were > or =16 mm long. Clinical data have been analyzed for 1,989 of the patients (23.9%) receiving the Endeavor ZES in this registry, with 30-day clinical outcomes available for 1,985 of these 1,989 patients (99.8%). The acute procedure success rate in these patients was 98.6%, comparable with procedure success rates observed in previous Endeavor ZES clinical trials. The 30-day rate of MACE in these patients was just 1.7%, comparable with 30-day rates of MACE observed in previous ENDEAVOR clinical trials. In an early analysis of a subgroup of patients enrolled in the E-Five Registry, the Endeavor ZES demonstrated encouraging acute and 30-day outcomes in a real-world population of patients who underwent single-vessel or multivessel percutaneous coronary intervention.

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.

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.