Leg Ischemia Research Articles

Akut Bacak İskemisinin Hibrit Yaklaşımla Başarılı Tedavisi

Akut Bacak İskemisinin Hibrit Yaklaşımla Başarılı Tedavisi

Risk factors to predict leg ischemia in patients undergoing single femoral artery cannulation in minimally invasive cardiac surgery.

In peripheral cannulation for cardiopulmonary bypass, there is always a risk of ischemia in the extremities, caused by femoral artery cannulation. This report aimed to evaluate the outcome and the risk factors in patients undergoing minimally invasive cardiac surgery in mitral valve surgery. We retrospectively reviewed all minimally invasive mitral valve surgery at our institute from May 2014 to December 2016. Operative outcomes and intra-operative monitoring for distal leg saturation were measured by the near-infrared spectroscopy values. For post-operative outcomes, the creatinine phosphorus kinase level was measured for the assessment of leg ischemia. Risk factors were evaluated for the elevation of post-operative creatinine phosphorus kinase. There were 162 patients who underwent single femoral artery cannulation for minimally invasive mitral valve surgery. The mean operation, cardiopulmonary bypass and aortic cross-clamp time were 212±44, 124±30, 76.6±22 minutes (min), respectively. The factors related to increased creatinine phosphorus kinase were male, body mass index, larger cannula size, operation time, cardiopulmonary bypass time and aortic cross-clamp time. The measurement of minimum near-infrared spectroscopy values did not show any association with creatinine phosphorus kinase elevation. There were significant associations between body mass index, cannula size and operation time and post-operative creatinine phosphorus kinase increase by multiple regression analysis. Two male patients had extremely high post-operative creatinine phosphorus kinase (18188 U/L and 16831 U/L) and they had high body mass index, large cannula size and longer operation time. In peripheral cannulation for minimally invasive cardiac surgery, body mass index, cannula size and operation time can be considered as risk factors for leg ischemia.

TCTAP C-175 Successful PTA of an End-stage Critical Limb Ischemia by Deep Venous Arterialization Technique

### Patient Initials or Identifier Number Mrs. K. ### Relevant Clinical History and Physical Exam This 72 year-old lady with underlining hypertension, type 2 diabetes, ESRD s/p regular H/D, CAD s/p PTCA was admitted during March 2017 for PAOD with critical limb ischemia of left lower leg with

Neuronal nitric oxide synthase expression is increased, but contraction‐induced phosphorylation is impaired in hindlimb muscles of rats with femoral artery ligation

Patients with peripheral artery disease experience repeated bouts of leg ischemia and reperfusion, promoting oxidative stress and inflammation in the affected muscles. While these conditions can reduce nitric oxide (NO) bioactivity, little is known about the effect of intermittent ischemia on neuronal NO synthase (nNOS), which is the main source of NO in contracting muscle. Reactive oxygen species (ROS) can disrupt nNOS signaling in muscle by reducing sarcolemmal nNOS, uncoupling nNOS, and impairing nNOS phosphorylation. We recently reported that oxidative stress occurs in the contracting hindlimbs of rats with femoral arteries that were ligated (LIG) for 72 h compared to rats with freely perfused (FP) femoral arteries. Therefore, in this study, we sought to determine if nNOS expression and regulation are disrupted in the hindlimb muscles of rats after femoral artery ligation. In skeletal muscles from FP or LIG hindlimbs of male Sprague Dawley rats, we measured protein expression of the NADPH oxidase subunit p67phox, cytosolic and mitochondrial superoxide dismutase (SOD1, SOD2), total nNOS, and nNOS dimerization. We also assessed nNOS phosphorylation (S1416) in resting muscle and after 10 min of rhythmic contractions. Consistent with our recent findings, p67phox was increased in muscles from LIG vs FP hindlimbs (plantaris, +160±55%, p<0.05; soleus, +418±236%, p=0.06), suggesting that NADPH oxidase is a significant source of ROS in LIG skeletal muscle. We also found that SOD1 was decreased (−13±2%, p<0.05) and SOD2 was increased (+52±18%, p=0.05) in the soleus but not plantaris muscles of LIG vs FP hindlimbs. This suggests that mitochondria may contribute to the increased ROS in oxidative muscle of the LIG hindlimbs. Surprisingly, nNOS was increased in soleus (+48±10%, p<0.05) and plantaris (+28±12%, p<0.05) muscles of LIG vs FP hindlimbs. Immunohistochemistry of the plantaris muscles confirmed that sarcolemmal nNOS localization was retained in the LIG hindlimbs. Although nNOS monomer levels increased in LIG vs FP muscles (soleus, +53±19%; plantaris, +36±12%; both p<0.05), similar increases in dimer levels resulted in unchanged nNOS dimer to monomer ratios, suggesting that nNOS remained coupled. Contraction of FP hindlimbs increased nNOS phosphorylation (+199±106%, p<0.05 vs rest), but this post‐transcriptional regulation was disrupted in muscle from LIG hindlimbs (+44±50%, p>0.05 vs rest). We then assessed signaling by the metabolic regulator AMP‐activated protein kinase (AMPK), which is known to phosphorylate nNOS. Total AMPK was unchanged in muscle from LIG vs FP hindlimbs, but the increased AMPK T172 phosphorylation seen in contracting muscle from FP hindlimbs (+21±6%, p<0.05 vs rest) was absent in muscle from LIG hindlimbs. Impaired AMPK regulation was confirmed by evaluating another known target, acetyl‐CoA carboxylase S79 phosphorylation (FP, +153±52%, p<0.05 vs rest; LIG, +49±25%, p>0.05 vs rest). Our findings suggest that impaired nNOS phosphorylation during contraction may contribute to reduced NO bioactivity in the muscles of the LIG hindlimb and raise the possibility that nNOS signaling might be restored by treatment with AMPK activators.Support or Funding InformationNIH P01 HL134609This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

PP-158 - Femoro-Popliteal Bypass With Local Anesthetic Is Possible?: Case Reports

Peripheral arterial disease (PAH) due to atherosclerosis is seen in 30% of the population over 65 years of age. Acute arterial embolism in chronic PAH is one of the most common causes of emergency in this age group. We aimed to present two patients had critical leg ischemia who underwent femoro popliteal bypass with local anesthesia for emergency acute arterial embolism on chronic PAH.

PP-167 - A Rare Cause of Acute Leg İschemia: Popliteal Artery Aneurysm

Introduction: Popliteal artery aneurysms are rarely seen, but thromboembolic complications they may cause may also lead to loss of intact extremity. Primary complications include rupture, distal embolization, and thrombosis. Post-thrombosis acute leg ischemia may be the first clinical sign.

OP-492 - Impact of the Chronic Repetitive Leg Ischemia on Left Ventricular Function and Severity of Coronary Atherosclerosis in Patients with Acute Coronary Syndrome

OP-492 - Impact of the Chronic Repetitive Leg Ischemia on Left Ventricular Function and Severity of Coronary Atherosclerosis in Patients with Acute Coronary Syndrome

Evaluation of Collateral Source Characteristics With 3-Dimensional Analysis Using Micro-X-Ray Computed Tomography.

BackgroundCollateral arteries provide an alternative blood supply and protect tissues from ischemic damage in patients with peripheral artery disease. However, the mechanism of collateral artery development is difficult to validate.Methods and ResultsCollateral arteries were visualized using micro–x‐ray computed tomography. Developmental characteristics were assessed using confocal microscopy. We conducted a single‐center, retrospective, observational study and assessed the dilatation of collateral arteries on ischemic sides. We quantified the vascular volume in both ischemic and nonischemic legs. A prominent increase in vascular volume was observed in the ischemic leg using a murine hind‐limb ischemia model. We also performed qualitative assessment and confirmed that the inferior gluteal artery functioned as a major collateral source. Serial analysis of murine hind‐limb vessel development revealed that the inferior gluteal artery was a remnant of the ischial artery, which emerged as a representative vessel on the dorsal side during hind‐limb organogenesis. We retrospectively analyzed consecutive patients who were admitted for the diagnosis or treatment of peripheral artery disease. The diameter of the inferior gluteal artery on the ischemic side showed significant dilatation compared with that on the nonischemic side.ConclusionsOur findings indicate that an embryonic remnant artery can become a collateral source under ischemic conditions. Flow enhancement in the inferior gluteal artery might become a novel therapeutic approach for patients with peripheral artery disease.

Risk of Mortality After Resolution of Spinal Malperfusion in Acute Dissection

Spinal cord ischemia (SCI) may develop in patients presenting with acute aortic dissection. We sought to determine how SCI and its recovery affect outcomes. We reviewed patients with SCI in acute type A aortic dissection (ATAAD) and acute type B aortic dissection (ATBAD) from September 1999 to May 2014. SCI was defined as paraplegia or paraparesis present on admission. Monoparesis/plegia, paraesthesia, or numbness was defined as ischemic neuropathy. All ATBAD patients were managed with antiimpulse therapy, with selective intervention for rupture, rapid aortic expansion, malperfusion, or intractable pain. ATAAD patients were managed with urgent proximal aortic replacement. Neurologic symptoms were present in 178 (18.2%) of 978 acute dissections (482 ATAAD and 496 ATBAD). Of these 178 patients, SCI presented in 52 patients (29.2%; 80.1% male; mean age, 57 years). On admission paraplegia was present in 24 (46.2%), paraparesis in 10 (19.2%), paresthesia/numbness in 27 (51.9%), and leg ischemia in 25 (48.1%). Aortic operations were performed in 27 SCI patients (51.9%). Symptom resolution was seen in 30 (57.7%). The 30-day mortality was 19.2% and was significantly less in those with resolution of SCI (6.7% vs 36.4%, p= 0.012). When surgical intervention was required in ATBAD with SCI, mortality was 50% (p= 0.039). SCI and symptom resolution significantly affected overall survival. SCI is associated with significantly increased risk of overall mortality (hazard ratio, 2.9; p < 0.001), and SCI resolution completely offsets this risk (hazard ratio, 0.28; p= 0.003). These effects were consistent between ATAAD and ATBAD (p= 0.554). SCI in acute aortic dissection portends a poor prognosis. However, reversal of deficits is associated with a long-term survival outcome comparable to patients unaffected with SCI.

Clinical Outcomes of Adult Patients Who Receive Extracorporeal Membrane Oxygenation for Postcardiotomy Cardiogenic Shock: A Systematic Review and Meta-Analysis

To investigate the clinical outcomes of adult patients receiving extracorporeal membrane oxygenation (ECMO) for postcardiotomy cardiogenic shock (PCS). Meta-analysis of 20 observational studies. Hospitals that perform cardiac surgery. The study included 2,877 PCS patients undergoing ECMO from 20 observational studies. ECMO use. Twenty observational studies were selected for final analysis. The pooled survival rate to hospital discharge was 34.0% (30.0%-38.0%) in PCS patients receiving ECMO. The pooled 1-year survival rate was 24.0% (19.05%-30.0%). The pooled midterm survival rate was 18.0% (11.0%-27.0%). The pooled rate of leg ischemia was 14.0% (10.0%-20.0%). The pooled rate of redo surgery was 50.0% (32.0%-68.0%). The pooled rate of renal failure was 57.0% (47.0%-66.0%). The pooled rate of neurologic complications was 16.0% (13.0%-20.0%). The pooled rate of infection was 31.0% (22.0%-41.0%). Most of the included studies commonly revealed that age >65 years, pre-ECMO or post-ECMO blood lactate, renal insufficiency, a longer duration of ECMO, and neurologic complications were risk factors of in-hospital mortality in PCS patients undergoing ECMO. The short-term and midterm survival rates of PCS patients treated with ECMO were disappointingly low, and post-ECMO complication rates were relatively high.

External Validation and Evaluation of Reliability of the FARP2 Score to Predict Early Graft Failure after Infrainguinal Bypass

To evaluate the accuracy of the FARP2 (female gender [F], bypass after a previous angioplasty [A], Redo bypass [R], and Pedal bypass [P2]) scoring system in predicting early graft failure (EGF) after infrainguinal bypass surgery (IBS). Charts of patients who underwent IBS between January 2014 and January 2017 in 2 tertiary academic centers were evaluated retrospectively. In follow-ups, 1 week after operation, detailed physical examination was done, Doppler ultrasonography was performed 1 month after operation, and integrity of the graft was evaluated. Calculation of FARP2 score was performed by a single surgeon (M.S.) who was well informed regarding FARP2 scoring system. The FARP2 scoring system was evaluated as following: female gender 1 point, bypass after a previous angioplasty 1 point, redo bypass 1 point, and pedal bypass 2 points. Totally, 231 patients (180 men and 51 women) were enrolled in the study. The mean FARP2 score was 0.52±0.73. The graft occlusion occurred in 23 patients (10%). Presence of critical leg ischemia was lower in patients who faced early graft occlusion (P=0.002). On the other hand, Rutherford classification score was significantly higher in patients who did not face graft occlusion (4.1 vs. 3.4, P=0.007). Moreover, unsuccessful angioplasty history and history of previous surgery were more common in that group (P<0.001 and P<0.001, respectively). None of the patients faced acute pulse loss, numbness loss, or ulcerative lesion after unsuccessful angioplasty. The mean interval between unsuccessful angioplasty and bypass was 1±1.2days in our study, which may have a role to prevent undesirable clinical consequences. The FARP2 score was 1.5±1.2 and 0.4±0.6 in patients who faced graft occlusion and in patients without occlusion (P<0.001). Multivariate regression analysis identified that critical leg scheme, presence of unsuccessful angioplasty history, and history of previous bypass operation were found as a predictive factor for EGF (P=0.044, P<0.001, and P=0.003, respectively). Finally, our study demonstrated that patients with FARP2 score 3-4 have 2.88-fold increased graft occlusion risk when compared with patients with FARP2 score 1-2. Our study externally validates that the FARP2 scoring system is related with EGF after IBS. The FARP2 score may be an effective practice in prediction of EGF in patients with peripheral arterial bypass surgery.

A Phase 1 Study of a Novel Bidirectional Perfusion Cannula in Patients Undergoing Femoral Cannulation for Cardiac Surgery

Leg ischemia is a serious complication of femoral artery cannulation. The primary aim of this study was to assess the safety and efficacy of a novel bidirectional femoral arterial cannula (Sorin Group USA, a wholly owned subsidiary of LivaNova PLC, Arvada, CO USA) that provides both antegrade and retrograde flow, in patients undergoing peripheral cannulation for cardiopulmonary bypass during cardiac surgery. Patients undergoing routine cardiac surgery requiring femoral artery cannulation for cardiopulmonary bypass were identified preoperatively. Informed written consent was obtained in all cases. Bidirectional cannula insertion used either a surgical cut-down and wire through needle approach or a percutaneous technique. Flow in the superficial femoral artery was assessed using Doppler ultrasound after commencement of cardiopulmonary bypass. Lower limb perfusion was assessed using reflectance near-infrared spectroscopy to measure regional oxygen saturations in the cannulated limb during cardiopulmonary bypass. Fifteen patients (median age = 61.3 years, range = 26-79 years, 10 males, 5 females) underwent femoral arterial cannulation using the novel bidirectional femoral cannula between August 2016 and May 2017. Fourteen cannulae were inserted directly into the femoral artery via a surgical cut-down and wire through needle technique. One bidirectional cannula was inserted using a percutaneous insertion technique. Indications included minimally invasive mitral and aortic valve surgery, thoracic aortic aneurysm repair, and redo cardiac surgery. The median duration of cardiopulmonary bypass was 129 minutes (range = 53-228 minutes). The cannula was inserted and positioned without difficulty in 14 of 15 patients. Incorrect sizing and arterial spasm prevented correct cannula positioning in one patient. Antegrade flow in the superficial femoral artery was observed on Doppler ultrasound in 12 of 12 patients in which this was performed. Continuous stable distal perfusion was demonstrated in the cannulated limb in 14 of 15 patients. No procedural complications occurred in the immediate or convalescent postoperative period. This study demonstrates that in patients undergoing femoral arterial cannulation for cardiopulmonary bypass during cardiac surgery, the use of a novel bidirectional cannula is safe and easy to insert and provides stable distal perfusion of the cannulated limb. Use of the device should largely obviate the need to insert a separate downstream perfusion cannula or use other techniques to protect against lower limb ischemia. Further research on a larger scale and in different patient populations is now warranted.

Effect of Impulsive Compression Treatment on Postoperative Complications After Open Peripheral Vascular Revascularization (In Situ): Protocol for a Randomized Control Trial

BackgroundIn patients with critical leg ischemia (CLI), the standard operative choice is an in situ bypass to the lower extremity to improve the patients´ prognosis and quality of life. Postoperative complications after surgery occur in 18 % of the patients, prolonging hospitalization and convalescence. The main operative complication is edema. This can be prevented by early mobilization or stimulation of the natural venous pump in the leg.ObjectiveTo investigate whether compression therapy with foot pump reduces postoperative edema, facilitates wound healing of the operation wounds, promotes healing of ischemic ulcers, and shortens hospitalization, increasing and improving the patient’s subjective quality of life faster.MethodsThe protocol is designed as a randomized, unblinded prospective study with 50 patients in each group. Standard postoperative routines after bypass surgery, including short-stretch bandaging of the operated legs, are compared to supportive stimulation of the venous pump by an impulsive compression foot pump. The postoperative edema of the leg is measured 10 cm below the patella and 8 cm proximal to the medial malleolus. Measurements are performed preoperatively, 1 and 4 days postoperatively and at discharge.ResultsThe primary endpoint is reduction of leg edema by at least 50%. The secondary endpoint includes earlier mobilization in the pump group and decreased length of stay in hospital. Quality of life is evaluated through the European Health Related Quality of Life Questionnaire 5 Dimensions (EQ-5D) and Vascular Quality of Life Questionnaire-6 (VascuQol-6) questionnaires. The start of the study is February 1, 2018, and the end of the study is February 1, 2020. First results will be available April 2020.ConclusionsIn orthopedic surgery of the lower extremities, the use of foot pumps has shown a reduction of edema and thrombosis in risk patients. Although important positive effects may be expected after vein bypass surgery, no reports have yet investigated the use of the device in vascular-operated patients and no analysis or meta Cochrane reviews are available in this field.Trial RegistrationClinicalTrials.gov NCT03192982; https://clinicaltrials.gov/ct2/show/NCT03192982 (Archived by WebCite at http://www.webcitation.org/6xMZJ06dw)

Hyperbaric Oxygen for Ischemic Diabetic Foot Ulcers

Evidence about the effectiveness of hyperbaric oxygen therapy (HBOT) in patients with chronic ischemic leg ulcers is conflicting. In this trial from

Intra-aortic balloon pump experience: a single center study comparing with and without sheath insertion.

Introduction: The mechanical circulation support used in treatment of low cardiac output at most is the intra-aortic balloon pump (IABP). Its usage fields are the complications occurring due to ischemic heart disease, disrupted left ventricle function, and the low cardiac output syndrome occurring during coronary artery by-pass surgery. Methods: During 28 years from 1985 to 2013, IABP support has been implemented to 3135 patients in our cardiac surgery operating theater and intensive care unit. The mean age of the patients was 61.4 ± 13.2 years (16-82). 2506 patients (80%) were the ones whom the cardiac surgery has been implemented. IABP support has been provided for 629 (20%) patients for medical treatment. We utilized IABP most frequently in coronary artery patients (70%). The first choice for placing the balloon catheter is the femoral artery in 3093 cases (98.7%). Results: The most frequently observed balloon complication was the lower extremity ischemia in 383 cases (12.2%).The leg ischemia was statistically significantly more frequent in patients with sheath (P=0.004). The extremity ischemia has developed in 4 of 12 patients with balloon placed from upper extremity. The local bleeding and balloon rupture were more frequent in patients whom the balloon has been placed without sheath. The mortality due to IABP has occurred in only 5 patients. Conclusion: Despite increase in IABP usage frequency rapidly, the complications due to catheter are still seen. We believe that the leg ischemia that is the most frequently seen complication can be prevented via IABP use without sheath.

Acute Arterial Occlusion after Treatment of Heart Failure

Arterial occlusion is a rare, serious complication in the treatment of acute decompensated heart failure with loop diuretics. A 66- year old male patient with acute decompensated heart failure was treated with loop diuretics after which occlusion of the left side of the patients’ aortic bifurcation prosthesis occurred. For acute leg ischemia a thrombectomy with a high mortality risk was performed after which perfusion of the leg increased and the clinical condition of the patient improved rapidly. Thus to improve the cardiac condition in a patient suffering from decompensated heart failure and acute arterial occlusion a multidisciplinary approach is necessary.

Local and Lower Limb Complications during and after Femoral Cannulation for Extracorporeal Life Support.

The extracorporeal life support system (ECLS) system is a lifesaving option for patients in pulmonary and/or cardiac failure. We reviewed our data on local complications in the leg and groin during and after ECLS explantation. Patients were included when an ECLS was cannulated in the groin and the ECLS was successfully weaned and explanted. Data were collected retrospectively in patients from January 2013 to January 2016. In this study, 90 patients were included; 39 (43%) ECLS were implanted with surgical cut down and 51 (57%) ECLS were implanted percutaneously. Most patients needed ECLS support following cardiac surgery: cut down: 25 (64%) versus percutaneous: 28 (55%) (p = 0.40). A distal leg perfusion cannula was implanted simultaneously in 61 (68%) patients (cut down: 25 [64%] vs. percutaneous: 36 [71%], p = 0.36). Distal leg ischemia was diagnosed in a total of 10 (11%) patients (cut down: 2 [5%] vs. percutaneous: 8 [16%], p = 0.18). Of those 10 patients, 5 patients had leg ischemia despite a distal leg perfusion cannula in place (cut down: 1 [3%] vs. percutaneous: 4 [8%], p = 0.38). Revascularization was successfully achieved in all patients and no amputations had to be performed. Similar rates of wound healing disorders were observed in both groups: cut down: 11 (28%) versus percutaneous: 10 (20%) patients (p = 0.45). Surgical and percutaneous implantation and explantation of ECLS are safe and feasible with comparable complication rates, including wound healing disorders. We recommend that a lower limb perfusion cannula should be placed to prevent leg ischemia. Surgical cut-down placement of the distal leg perfusion cannula may reduce the incidence of distal leg ischemia compared with percutaneous distal leg cannula implantation. Correct placement of the cannula should be controlled.

Single-centre experience with the Impella CP, 5.0 and RP in 109 consecutive patients with profound cardiogenic shock.

Short-term mechanical circulatory support is increasingly used in the management of cardiogenic shock, but data from controlled studies are sparse. Thus, real-life data on complication rates and predictors of adverse outcome are important. The objective of this study was to analyse the experience with Impella devices in the management of profound cardiogenic shock. A retrospective study of 109 consecutive patients with severe shock after myocardial infarction, acute heart failure, or cardiac surgery. Possible device-related complications were registered and predictors of death while on Impella support and within 180 days were identified. In 79 patients (72%) cardiogenic shock was caused by myocardial infarction, acute heart failure in 16 (15%) and post-cardiotomy shock in 14 patients (13%). Thirty-five patients (32%) were comatose after cardiac arrest and in seven, the Impella was placed during chest compression. Mean age was 62±12 years, mean arterial pressure was 57±13 mmHg, pH 7.19±0.17 and lactate 7.5±5.7 mmol/l (range 1.8-30.0 mmol/l) at placement. During Impella therapy, 26 patients (28%) died among patients with myocardial infarction or acute heart failure. Of data available prior to placement lactate (hazard ratio 1.14, 95% confidence interval 1.04-1.25, P=0.004) was the only predictor of death on support. During support, five patients (5%) developed leg ischaemia requiring intervention. Bleeding from the Impella insertion site was seen in 14 patients (13%). Impella treatment is feasible in profound cardiogenic shock at an acceptable rate of complications. Despite an aggressive approach to restore cardiac output, mortality was high. Besides the severity of lactic acidosis there were no strong predictors of early death.

Therapeutic Benefit and Gene Network Regulation by Combined Gene Transfer of Apelin, FGF2, and SERCA2a into Ischemic Heart.

Despite considerable advances in cardiovascular disease treatment, heart failure remains a public health challenge. In this context, gene therapy appears as an attractive approach, but clinical trials using single therapeutic molecules result in moderate benefit. With the objective of improving ischemic heart failure therapy, we designed a combined treatment, aimed to simultaneously stimulate angiogenesis, prevent cardiac remodeling, and restore contractile function. We have previously validated IRES-based vectors as powerful tools to co-express genes of interest. Mono- and multicistronic lentivectors expressing fibroblast growth factor 2 (angiogenesis), apelin (cardioprotection), and/or SERCA2a (contractile function) were produced and administrated by intramyocardial injection into a mouse model of myocardial infarction. Data reveal that combined treatment simultaneously improves vessel number, heart function parameters, and fibrosis prevention, due to FGF2, SERCA2a, and apelin, respectively. Furthermore, addition of SERCA2a in the combination decreases cardiomyocyte hypertrophy. Large-scale transcriptome analysis reveals that the triple treatment is the most efficient in restoring angiogenic balance as well as expression of genes involved in cardiac function and remodeling. Our study validates the concept of combined treatment of ischemic heart disease with apelin, FGF2, and SERCA2a and shows that such therapeutic benefit is mediated by a more effective recovery of gene network regulation.

Extracorporeal Circulatory Support in Acute Coronary Syndromes: A Systematic Review and Meta-Analysis.

Extracorporeal circulatory support is a life-saving technique, and its use is increasing in acute coronary syndromes. A meta-analysis on pooled event rate of short-term mortality and complications of acute coronary syndrome patients treated with extracorporeal circulatory support was performed. Articles were searched in MEDLINE, Cochrane Library, Google Scholar, and Biomed Central. Inclusion criteria were observational studies on acute coronary syndrome patients treated with extracorporeal circulatory support. Primary outcome was short-term mortality. Secondary outcomes were extracorporeal circulatory support-related complications, causes of death, long-term mortality, and bridge therapy. Sixteen articles were selected. Data about clinical characteristics, acute coronary syndrome diagnosis and treatment, extracorporeal circulatory support setting, outcome definitions, and event rate were retrieved from the articles. Random effect meta-analytic pooling was performed reporting results as a summary point estimate and 95% CI. A total of 739 patients were included (mean age, 59.8 ± 2.9). The event rate of short-term mortality was 58% (95% CI, 51-64%), 6-month mortality was affecting 24% (95% CI, 5-63%) of 1-month survivors, and 1-year mortality 17% (95% CI, 6-40%) of 6-month survivors. The event rates of extracorporeal circulatory support-related complications were acute renal failure 41%, bleeding 25%, neurologic damage in survivors 21%, sepsis/infections 21%, and leg ischemia 12%. Between causes of death, multiple organ failure and brain death affected respectively 40% and 27% of patients. Bridge to ventricular assistance device was offered to 14% of patients, and 7% received a transplant. There is still a high rate of short-term mortality and complications in acute coronary syndrome patients treated with extracorporeal circulatory support. New studies are needed to optimize and standardize extracorporeal circulatory support.