Laurent Barandon

Epicardial deposition of endothelial progenitor and mesenchymal stem cells in a coated muscle patch after myocardial infarction in a murine model

OBJECTIVESnTo assess, using an in vivo engraftment strategy combining bone marrow cell (BMC) transplantation and tissue cardiomyoplasty, the functional outcome of distinct vascular progenitor cell therapy (endothelial progenitor (EPC) and mesenchymal stem (MSC) cells) at distance of myocardium infarction (MI). The study was also designed to test whether scaffold mixing progenitors with unfractionated BMC could improve progenitor recruitment in the damaged myocardium.nnnMETHODSnTo track engrafted progenitor cells in vivo, cultured murine MSC and EPC were transduced with eGFP lentiviruses. Thirty days after cryogenical induction of MI, C57BL/6J mice were randomized to receive muscle patch placement coated or not (control group), labeled EPC or MSC mixed to the ration of 1:10, or not with unfractionated BMC. Two weeks after transplantation, cardiac function was recorded and heart sections were examined to detect GFP-labeled progenitor cells and analyze cell differentiation.nnnRESULTSnThis study showed that either type of mono cell therapy improved angiogenesis and cell survival in the scar but only MSC exhibited the capacity to invade the scar. We found no evidence of myocardial or vascular regeneration from progenitor cells. Engraftment of the progenitors/unfractionated BMC mix increased repopulation and thickness of the scar.nnnCONCLUSIONnCombined therapy with unfractionated BMC and expanded MSC appeared thus promising for scar repopulation.

Hypoxia-preconditioned mesenchymal stromal cells improve cardiac function in a swine model of chronic myocardial ischaemia

OBJECTIVESnCell loss during cardiac injection and hostility of the host-tissue microenvironment have the potential to diminish the overall effect of stem cell therapy. The purposes of this study were to evaluate the effect of a hypoxic preconditioning of mesenchymal stromal cells (MSC), to determine its safety and effectiveness, and to improve the efficacy of cell therapy using MSC in the setting of chronic myocardial ischaemia in swine.nnnMETHODSnMyocardial ischaemia was induced by an ameroid constrictor. Human MSC were cultured under normoxic (20% O2) or hypoxic conditions (1.5% O2) before transplantation. One month after ischaemia, pigs were randomly assigned to saline injection (sham), and 1 × 10(6)/kg normoxic or hypoxic MSC transplantation into the ischaemic inferior-lateral zone.nnnRESULTSnTwenty-seven pigs were operated on and the mortality rate was 33.3%. The remaining 18 animals were randomly assigned to sham (n = 4), normoxic (n = 8) or hypoxic MSC (n = 6) treatment. Global systolic (left ventricle ejection fraction, P = 0.04) and diastolic (E/Ea, P = 0.008) functions were increased in the hypoxic group compared with other groups. The peak of 2-dimensional longitudinal strain was less altered in the hypoxic group compared with other groups (P < 0.001). Haemodynamic data showed that dP/dT max was improved in the hypoxic group compared with the other group (P < 0.01). Capillary density was increased in the hypoxic group (P = 0.001). MSC density was significantly higher in the ischaemic zone in the hypoxic group (P < 0.01).nnnCONCLUSIONnMSC engraftment with hypoxic preconditioning significantly improves capillary density and cell survival, resulting in improvement in global, regional and diastolic left ventricular functions. This highlights the therapeutic potential of transplanting hypoxic-preconditioned MSC in the setting of chronic ischaemic heart failure.

Characteristics of Ventricular Tachycardia Ablation in Patients With Continuous Flow Left Ventricular Assist Devices

Background—Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device. Methods and Results—All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230–740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT. Conclusions—Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.

The Use of Impella 2.5 in Severe Refractory Cardiogenic Shock Complicating an Acute Myocardial Infarction

OBJECTIVESnTo investigate the outcome of patients with acute myocardial infarction (AMI) complicated by refractory cardiogenic shock (CS) who underwent mechanical circulatory support with Impella 2.5.nnnBACKGROUNDnAMI complicated by CS remains a highly fatal condition. A potent and minimally invasive left ventricular assist device might improve patient outcomes.nnnMETHODSnWe analyzed the procedural characteristics and outcomes of 22 consecutive patients who underwent, between July 2008 and December 2012, a percutaneous coronary intervention and Impella 2.5 support for AMI complicated by CS refractory to first-line therapy with inotropes and/or Intra-aortic balloon pump.nnnRESULTSnIn this analysis, patients were relatively young with a mean age of 57.9 ± 11.6 year old and 59.1% were male. The majority of patients (77.3%) were admitted in CS and 40.9% sustained cardiac arrest prior to admission. Hemodynamics improved significantly upon initiation of support, end-organ and tissue perfusion improved subsequently demonstrated by a significant decrease in lactate levels from 6.37 ± 5.3u2009mmol/L to 2.41 ± 2.1u2009mmo/L, (Pu2009= u20090.008) after 2 days of support. Thirteen (59.1%) patients were successfully weaned-off Impella 2.5 and 4 (18.2%) were transitioned to another device. We observed a functional recovery of the left ventricle when compared to baseline (43u2009±u200910% vs. 27u2009±u20099%, Pu2009<u20090.0001). The survival rate at 6 months and 1 year was 59.1% and 54.5%, respectively.nnnCONCLUSIONnImpella 2.5 was initiated as a last resort therapy to support very sick patients with refractory CS after failed conventional therapy. The use of the device yielded favorable short and mid-term survival results with recovery being the most frequently observed outcome.

Echocardiographic analysis with a two-dimensional strain of chronic myocardial ischemia induced with ameroid constrictor in the pig

Despite much progress in the medical management of myocardial ischemia, several problems remain and experimental models help to improve our understanding of the pathophysiology involved in this domain. The ameroid constrictor model is the most widely used to create ischemia but evaluation of patent ischemia is still under debate. In the present study, we describe the potential of a two-dimensional (2D) strain for experimentally evaluating myocardial ischemia in the pig. An ameroid constrictor was placed around the circumflex artery in 30 pigs. Angiography showed 90% stenosis at one and two months. Left ventricular function was moderately altered and associated with mitral valve insufficiency in 30% of cases. Longitudinal and circumference strains were dramatically modified in the ischemic inferior-lateral zone compared to the healthy anterior zone (P<0.01) at one and two months. We correlated these results to myocardial ischemia by using contrast echocardiography, which showed a significant reduction in myocardial perfusion in the ischemic zone compared to the uninjured area, and by using histological analysis. We showed that evaluation of the 2D strain could be an interesting approach for assessing myocardial ischemia after ameroid constrictor implantation. The 2D strain represents a useful tool for the evaluation of experimental models of myocardial ischemia.

After acute coronary syndrome, diabetic patients with peripheral vascular disease remain at high risk of cardiovascular events despite secondary prevention measures

BACKGROUNDnPeripheral vascular disease (PVD) is associated with a high risk of cardiovascular events after an acute coronary syndrome (ACS). The impact of suboptimal risk-factor control and drug prescription on morbidity and mortality rates in patients with PVD following an ACS remains to be established.nnnAIMSnTo assess whether a global atherosclerosis management programme and optimal secondary prevention could benefit high-risk PVD patients after an ACS.nnnMETHODSnA total of 851 ACS patients underwent an intensified intervention focusing on evaluating risk factors and atherosclerosis lesions, and on optimizing treatment and education. We compared its impact on long-term risk factors, medication observance and cardiovascular outcomes in patients with coronary artery disease (CAD) alone (n=715, 84.0%) and with both CAD and PVD (n=136).nnnRESULTSnAt a median follow-up of 18.6months, both groups reached recommended secondary prevention goals and showed no significant differences in rates of drug prescription. PVD was not associated with minor cardiovascular events (hazard ratio [HR] 1.32, 95% confidence interval [CI] 0.57-3.02) but remained independently associated with major (HR 2.15, 95% CI 1.12-4.13) and total (HR 1.76, 95% CI 1.05-2.93) cardiovascular events. Compared to patients with CAD alone, this risk was significantly higher in CAD patients with both PVD and diabetes (HR 2.87, 95% CI 1.52-5.43), but not in PVD patients without diabetes (HR 1.35, 95% CI 0.71-2.56) or diabetic patients without PVD (HR 1.11, 95% CI 0.68-1.81).nnnCONCLUSIONnDespite optimization of risk-factor control and drug prescription after ACS, patients with both PVD and diabetes carry a 2.9-fold higher risk of cardiovascular events at 18-month follow-up versus patients with CAD alone. This excess risk was not significant in PVD patients without diabetes or in diabetic patients without PVD.

Cardiopulmonary bypass during a second-lung implantation improves postoperative oxygenation after sequential double-lung transplantation.

OBJECTIVESnDuring sequential double-lung transplantation (DLT), the newly implanted first lung receives the entire cardiac output during the implantation of the second one. This may be responsible for the increased hydrostatic pressure that causes severe interstitial and alveolar edema that can lead to allograft dysfunction. The authors tested the hypothesis that CPB started after first graft implantation and before second recipient lung removal should improve post-transplantation oxygenation and clinical outcomes.nnnDESIGNnObservational during 2 consecutive 1-year periods.nnnSETTINGnUniversity hospital.nnnPARTICIPANTSnNine consecutive patients undergoing sequential DLT with CPB started after first graft implantation and before second recipient lung removal were compared to controls, who were 10 consecutive patients who underwent sequential DLT but without CPB the year before.nnnMEASUREMENTS AND MAIN RESULTSnOxygenation after transplantation was assessed. The use of CPB during the implantation of the second lung was associated with an increased mean postoperative ratio of PaO2 to the fraction of inspired oxygen at 1 hour (363±51 v 240±113, p = 0.01) and 6 hours (430±111 v 280±103, p = 0.03). The mean duration of CPB was 111±19 min. The occurrence of primary graft dysfunction and the need for extracorporeal membrane oxygenation tended to be lower, but did not reach significance. Similarly, mortality rate was comparable between both groups, as was the rate of blood transfusions.nnnCONCLUSIONSnThe authors results suggest that the use of CPB started after first graft implantation and before second recipient lung removal appears to benefit oxygenation and reduces the occurrence of severe pulmonary edema in the first transplanted lung.