Severe Ischemic Heart Disease Research Articles

Patients With Non-Obstructive Coronary Artery Disease and Polyvascular Disease. Sub-Analysis of the Real-World Registry KAMMA (Clinical Registry on Patient Population With Polyvascular Disease in the Russian Federation and Eurasian Countries).

To study the clinical status and data of laboratory and instrumental examination of patients with non-obstructive ischemic heart disease (IHD) and multifocal atherosclerosis (MFA) included in the KAMMA registry. The subanalysis included 1,893 IHD patients who underwent coronary angiography (CAG) and ultrasonic examination of peripheral arteries. Based on the CAG data, patients were divided into two groups: group 1, patients with obstructive coronary atherosclerosis (CA) (maximum stenosis ≥50% and/or history of percutaneous coronary intervention/coronary artery bypass grafting, n=1728; 91.3%) and group 2, patients with non-obstructive CA (maximum stenosis <50%, n = 165; 8.7%). A comparative analysis based on the degree of coronary obstruction in patients with verified IHD who were included in the KAMMA registry showed that 8.7% of them had coronary artery stenosis of less than 50%. The overwhelming majority of patients with non-obstructive CA had MFA affecting the brachiocephalic arteries in 94.3% and the lower extremity arteries in 40.2%. Among patients with non-obstructive IHD, women predominated; risk factors such as smoking and type 2 diabetes mellitus were less frequent in this group than in the obstructive IHD group. Patients with non-obstructive CA more frequently had a history of dyslipidemia; they had higher total cholesterol and non-high-density lipoprotein cholesterol; and they more frequently received moderate-intensity statin therapy than patients with obstructive CA (55.8% vs. 34.5%). Characteristic features of patients with non-obstructive CA were less severe IHD and less frequent history of acute coronary syndrome. However, the incidence of stroke, peripheral arterial thrombosis, and chronic arterial insufficiency of the lower extremities did not differ in groups 1 and 2, whereas the incidence of paroxysmal atrial fibrillation was higher in the non-obstructive IHD group. IHD patients without coronary obstruction also require assessment of the peripheral arterial status, as they may have advanced MFA, which should be taken into account when choosing the "aggressiveness" of therapy.

Follow-up of intramyocardial bone marrow mononuclear cell transplantation beyond 10 years

Bone marrow mononuclear cells (BMMCs) have been evaluated for their ability to improve cardiac repair and benefit patients with severe ischemic heart disease and heart failure. In our single-center trial in 2006–2011 we demonstrated the safety and efficacy of BMMCs injected intramyocardially in conjunction with coronary artery bypass surgery. The effect persisted in the follow-up study 5 years later. In this study, we investigated the efficacy of BMMC therapy beyond 10 years. A total of 18 patients (46%) died during over 10-years follow-up and 21 were contacted for participation. Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) and clinical evaluation were performed on 14 patients, seven from each group. CMRIs from the study baseline, 1-year and 5-years follow-ups were re-analyzed to enable comparison. The CMRI demonstrated a 2.1-fold larger reduction in the mass of late gadolinium enhancement values between the preoperative and the over 10-years follow-up, suggesting less scar or fibrosis after BMMC treatment (− 15.1%; 95% CI − 23 to − 6.7% vs. − 7.3%; 95% CI − 16 to 4.5%, p = 0.039), compared to placebo. No differences in mortality or morbidity were observed. Intramyocardially injected BMMCs may exert long-term benefits in patients with ischemic heart failure. This deserves further evaluation in patients who have received BMMCs in international clinical studies over two decades.

Esophageal stent dysfunction: unclogging the Red Sea.

Self-expandable metal stents (SEMS) have been widely used for the palliation of esophageal malignant dysphagia. Stent-related dysphagia is frequent and should raise the suspicion of stent migration, tumor ingrowth or overgrowth. In addition, bleeding has been reported in nearly 7% of patients. Nonetheless, this is the first case report of a complete stent obstruction by abundant blood clot formation. The authors present a 76-year-old male with severe ischemic heart disease and atrial fibrillation, requiring cardiac resynchronization therapy defibrillator and anticoagulation. After being diagnosed with metastasized squamous cell mid-esophageal cancer, he was proposed for chemotherapy and palliative esophageal stenting.

Abstract 13859: The Omics Signature of Human Pericardial Fluid Exosomes Reveals the Therapeutic Potential of APAF-1 Inhibition in Ischemic Heart Disease

Background: The human pericardial fluid (PF) contains heart-derived small extracellular vesicles (sEVs) able to induce vascular responses via microRNA (miR) transfer. People with diabetes (DM) are particularly at risk of severe ischemic heart disease (IHD) and might require personalized therapeutic treatment. Hypothesis: The PF-sEVs molecular profiling supports the identification of clinical-relevant therapeutic targets. Aims: 1) To characterize PF-sEVs of IHD patients with/out type-2 DM (T2DM) in comparison to controls; 2) to validate the emerging therapeutic target candidates. Methods: PF samples (n=12/group) were collected during cardiac surgeries, namely CABG (for IHD with/out DM groups) and mitral valve repair (non-IHD, non-DM control group). sEVs were prepared (SEC), quality controlled (Nanosight and Exoview) and submitted to untargeted proteomics and microRNA array (Exiqon) or validation experiments. miRNA-target prediction methods and integration of proteomics and transcriptomics via networks identified differentially expressed pathogenic proteins and their putative endogenous miRNA regulators. The emerging dysregulated miRNA/protein axis was investigated in vitro and in mice with myocardial infarction (MI) and with/out diet-induced T2DM. Results: the PF-EVs of IHD patients with DM showed increased APAF-1 and reduced let-7b-5p, a miR which we have demonstrated to repress APAF-1 by direct 3’-UTR-binding. Exposure of endothelial cells (ECs) to DM and IHD-mimicking culture conditions increases APAF-1 level, triggering apoptosis and reducing angiogenesis. The phenotype of ECs kept under disease-mimicking conditions was rescued by APAF-1 silencing (siRNAs) and by supplementation with either healthy PF-EV or LNPs carrying let-7b-5p as sole miR cargo. The synthetic APAF-1 inhibitor ZYZ-488 improved post-MI cardiac function (Vevo3100 echocardiography), increased capillary density and reduced EC apoptosis in the peri-infarct area of diabetic and non-diabetic mice of both sexes. Conclusions: PF-EVs represent a novel and privileged source for the discovery of clinical-relevant therapeutic targets. APAF-1 inhibition holds value for post-ischemic cardiac protection and repair, including in diabetic people.

Association between Serum Ferritin and Prognosis in Patients with Ischemic Heart Disease in Intensive Care Units.

Recent years have seen a clear link established between elevated ferritin levels and COVID-19 prognosis. However, the impact of heightened ferritin levels on the prognosis of individuals with severe ischemic heart disease remains uncertain. We utilized the MIMIC IV database to identify a cohort of ischemic heart disease patients who underwent serum ferritin testing. We conducted regression analyses, employed the overlap propensity score weighting model, and utilized the restricted cubic splines model to comprehensively investigate the associations between serum ferritin levels and clinical outcomes. Our cohort included 1173 patients with diagnosed ischemic heart disease, categorized into high and low serum ferritin groups. After meticulous adjustment for confounding factors in a fully adjusted model, the hazard ratios (HRs) for 90-day and 1-year mortality were 1.63 (95% CI: 1.27-2.09) and 1.49 (95% CI: 1.19-1.86), respectively, in the high-ferritin group compared to the low-ferritin group. Subsequent analyses with propensity score weighting confirmed these results. Remarkably, restricted cubic spline analysis revealed an almost linear relationship between log-transformed serum ferritin levels and the risk of both 90-day and 1-year all-cause mortality. Moreover, incorporating ferritin into conventional severity of illness scores significantly improved the area under the curve for both 90-day and 1-year mortality. This study provides compelling evidence regarding the prognostic significance of serum ferritin in predicting 90-day and one-year mortality rates among patients diagnosed with ischemic heart disease.

Ischemic strokes in COVID-19: risk factors, obesity paradox, and distinction between trigger and causal association.

Stroke has been described as a COVID-19 complication. However, its occurrence rate, risk factors, and causal relationships are still not well established. We describe the characteristics of confirmed COVID-19-related strokes among all cases of COVID-19 hospitalized in our health network, from November 1, 2020 to April 30, 2021. Risk factor analysis has been conducted for ischemic stroke (IS), which represents 92% of all confirmed cases of Covid-19-related strokes, and a "causal attribution to infection" classification is provided. In all, 62/4105 hospitalized COVID-19 patients had an acute stroke (1.51%). Severe COVID-19 (OR 2.27-CI 1.06-4.77; p = 0.032), atrial fibrillation (OR 3.65-CI 1.63-7.98; p = 0.001), and ischemic heart disease (OR 4.590-CI 1.714-12.137; p = 0.002) proved to be independent risk factors for IS, while obesity was a protective factor (OR 0.90-CI 0.82-0.97; p = 0.012). COVID-19 had a causal role in 32.1% of IS cases, was a relevant cofactor in 28.6% of cases of IS, and was a possible trigger in 39.3% of events. Our stroke occurrence rate is consistent with other population-based reports (range 0.34-2.7%). Prespecified peculiar clinical and radiological features allow the distinction between "IS caused by COVID-19" and "IS triggered by COVID-19." Clinical history of vascular diseases and risk factors is crucial in determining the risk of IS in patients with COVID-19. However, the protective effect of a BMI > 30 kg/m2 seems to suggest an obesity paradox.

Informal caregivers must open the door to information during heart surgery patients hospitalization. A qualitative study

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Despite the possibility of invasive procedures, open heart surgery is still recommended in cases of severe ischemic heart disease and valvular heart disease. National health authorities recommend that health care professionals in hospital should offer informal caregivers necessary learning and support for burdensome caring duties. Follow-up of heart surgery patients after discharge from hospital can be an informal caregiver challenge. There is a lack of studies on the informal caregivers’ experiences with information from health care professionals from before and during hospitalization. Purpose This study explores the informal caregivers of heart surgery patients experiences of information and communication from health care professionals before and during hospitalization. Methods Qualitative in-depth interviews were conducted in informal caregivers to patients, who had undergone open heart surgery. A semi-structured interview guide was used during videotelephony (Facetime), phone or face-to-face onsite interview. The settings were university hospitals in Norway and Denmark respectively and were carried out between November 2022 – January 2023. Data analysis in NVivo software tool, following Braun and Clarke`s 6-step thematic analysis process. Results A total of 12 informal caregivers, married or partnered, two men, mean age 65 years, were interviewed two to four weeks after the patient had been discharged to home following open heart surgery. Two main themes were identified: i) lack of preoperative information and ii) responsibility to chase for in-hospital communication. Informal caregivers must invite themselves to gain access to information before admission. Informal caregivers experienced being a team with the patient before admission and then be separated in the health care system. The information and communication were targeted to the patient. Therefore, it was necessary for informal caregivers to be communicatively strong and thereby force doors open to get needed information for themselves. For some informal caregivers it was manageable while others felt lost and withdrew. Conclusion(s) Informal caregivers to patients undergoing open heart surgery want to be part of the information process before and during hospital admission. They want to be in a team with the patient, but it requires an active invitation from health care professionals.

Autologous CD133 + Cells and Laser Revascularization in patients with severe Ischemic Cardiomyopathy.

We tested the hypothesis that targeted TMLR combined with intramyocardial injection of autologous CD 133+ progenitor cells is safe and feasible in patients with chronic ischemic cardiomyopathy (ICM) and no revascularization options. Eight male patients (age 62 ± 2.4years) with multivessel severe ischemic heart disease and no revascularization options were enrolled. Autologous CD 133 + endothelial progenitor cells were derived and purified from the bone marrow on the day of surgery using the clinical-grade closed CliniMACS system. Using a lateral thoracotomy approach, TMLR was performed, followed by transmyocardial transplantation of purified CD133 + cells (mean number of transplanted cells: 12.5 × 106) in the region surrounding the TMLR sites. These sites were selected based on ischemia on pre-procedure perfusion imaging. We performed clinical and myocardial perfusion imaging pre-procedure and then at 6- and 12-month follow-up. No major complications or death occurred during the procedure or during the peri-operative hospital stay. One patient died of cardiac cause 6months post-procedure. There was a reported short-term improvement in anginal and heart failure symptoms and a modest reduction in the ischemic score as assessed by perfusion imaging. Our phase 1 clinical study examining the combination therapy of targeted transmyocardial laser revascularization therapy and autologous CD133 + endothelial progenitor cells in patients with chronic ICM and no revascularization options demonstrates the feasibility and short-term safety of this combined approach and warrants future larger phase 2 randomized clinical studies.

Safety of Minimally Invasive Percutaneous Nephrolithotmy in High Risk Patients in Lateral Position - A Single Center Study

Objective: To assess the safety and efficacy of minimally invasive percutaneous nephrolithotomy with fluoroscopy aided renal access in the lateral position, in patients who were high-risk cases for anesthesia in prone position.
 Study Design: Prospective observational study.
 Place and Duration of Study: Armed forces institute of Urology, Rawalpindi, from Jan 2018 to Dec 2019.
 Methodology: Fifty-three patients with renal stones >1.8cm underwent minimally invasive percutaneous nephrolithotomy with fluoroscopy-guided renal access in the lateral position. All the patients were obese, some had severe ischemic heart disease, few had diabetes mellitus. All the patients were unfit for the prone position.
 Results: Successful renal access was achieved in all the patients (100%). The mean size of stone was 28 + 13.2 mm, with an average operative time being 55 ± 13.56 minutes and the mean hospital stay was 1.8 ± 2.3 days (range 2-4 days). No visceral or pleural injuries were documented. In addition, only two patients required postoperative transfusion. After procedure, the rate of complete stone clearance initially was 90.6%, which improved to 96% after single session of extracorporeal shockwave lithotripsy (ESWL). Only 2 (3.77%) patients had persistent residual stone fragment.
 Conclusion: Minimally invasive percutaneous nephrolithotomy with fluoroscopy-guided renal access in the lateral decubitus flank position, is safe and convenient in high-risk patients where prone position is contraindicated.

Ischiorectal Abscess Under Bilateral Pudendal Nerve Block for Perioperative Analgesia in a Patient with Severe Ischaemic Heart Disease- A Case Report

Anorectal abscess, an infection in the anal area is a potentially debilitating and painful condition requiring urgent drainage to prevent septicemia. Commonly performed under neuraxial anaesthesia, we report surgical drainage of bilateral ischiorectal abscess under bilateral pudendal nerve blocks and general anaesthesia in a patient with severe ischaemic heart disease. Through our case we add to the existing literature, the importance of administrating peripheral nerve block in highly co-morbid patients. Keywords: Anorectal abscess, Bilateral pudendal block, Severe ischaemic heart disease.

Energy-sparing by 2-methyl-2-thiazoline protects heart from ischaemia/reperfusion injury.

AimsCardiac ischaemia/reperfusion (I/R) injury remains a critical issue in the therapeutic management of ischaemic heart failure. Although mild hypothermia has a protective effect on cardiac I/R injury, more rapid and safe methods that can obtain similar results to hypothermia therapy are required. 2‐Methyl‐2‐thiazoline (2MT), an innate fear inducer, causes mild hypothermia resulting in resistance to critical hypoxia in cutaneous or cerebral I/R injury. The aim of this study is to demonstrate the protective effect of systemically administered 2MT on cardiac I/R injury and to elucidate the mechanism underlying this effect.Methods and resultsA single subcutaneous injection of 2MT (50 mg/kg) was given prior to reperfusion of the I/R injured 10 week‐old male mouse heart and its efficacy was evaluated 24 h after the ligation of the left anterior descending coronary artery. 2MT preserved left ventricular systolic function following I/R injury (ejection fraction, %: control 37.9 ± 6.7, 2MT 54.1 ± 6.4, P < 0.01). 2MT also decreased infarct size (infarct size/ischaemic area at risk, %: control 48.3 ± 12.1, 2MT 25.6 ± 4.2, P < 0.05) and serum cardiac troponin levels (ng/mL: control 8.9 ± 1.1, 2MT 1.9 ± 0.1, P < 0.01) after I/R. Moreover, 2MT reduced the oxidative stress‐exposed area within the heart (%: control 25.3 ± 4.7, 2MT 10.8 ± 1.4, P < 0.01). These results were supported by microarray analysis of the mouse hearts. 2MT induced a transient, mild decrease in core body temperature (°C: −2.4 ± 1.4), which gradually recovered over several hours. Metabolome analysis of the mouse hearts suggested that 2MT minimized energy metabolism towards suppressing oxidative stress. Furthermore, 18F‐fluorodeoxyglucose‐positron emission tomography/computed tomography imaging revealed that 2MT reduced the activity of brown adipose tissue (standardized uptake value: control 24.3 ± 6.4, 2MT 18.4 ± 5.8, P < 0.05). 2MT also inhibited mitochondrial respiration and glycolysis in rat cardiomyoblasts.ConclusionsWe identified the cardioprotective effect of systemically administered 2MT on cardiac I/R injury by sparing energy metabolism with reversible hypothermia. Our results highlight the potential of drug‐induced hypothermia therapy as an adjunct to coronary intervention in severe ischaemic heart disease.

Cardiac Scintigraphy and Screening for Transthyretin Cardiac Amyloidosis: Caveat Emptor.

Cardiac Scintigraphy and Screening for Transthyretin Cardiac Amyloidosis: Caveat Emptor.

Modification of the Association Between Severe Hypoglycemia and Ischemic Heart Disease by Surrogates of Vascular Damage Severity in Type 1 Diabetes During ∼30 Years of Follow-up in the DCCT/EDIC Study.

Literature suggests that severe hypoglycemia (SH) may be linked to cardiovascular events only in older individuals with high cardiovascular risk score (CV-score). Whether a potential relationship between any-SH and cardiovascular disease exists and whether it is conditional on vascular damage severity in a young cohort with type 1 diabetes (T1D) without apparent macrovascular and no or mild-to-moderate microvascular complications at baseline is unknown. We evaluated data of 1,441 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study volunteers (diabetes duration 1-15 years) followed for ∼30 years. Time-dependent associations between any-SH and ischemic heart disease (IHD: death, silent/nonfatal myocardial infarct, revascularization, or confirmed angina) and associations between interactions of any-SH with surrogates of baseline micro-/macrovascular damage severity and IHD were analyzed. Diabetes duration, steps on DCCT Early Treatment Diabetic Retinopathy Study severity scale (DCCT-ETDRS), Diabetes Complications Severity Index (DCSI), and CV-scores were considered as surrogates of baseline micro-/macrovascular damage severity. Without interactions, in the minimally adjusted model controlling for confounding bias by age and HbA1c, SH was a significant IHD factor (P = 0.003). SH remained a significant factor for IHD in fully adjusted models (P < 0.05). In models with interactions, interactions between SH and surrogates of microvascular complications severity, but not between SH and CV-score, were significant. Hazard ratios for IHD based on SH increased 1.19-fold, 1.32-fold, and 2.21-fold for each additional year of diabetes duration, DCCT-ETDRS unit, and DCSI unit, respectively. At time of IHD event, ∼15% of 110 participants with SH had high CV-scores. In a young cohort with T1D with no baseline macrovascular complications, surrogates of baseline microvascular damage severity impact the effect of SH on IHD. Older age with high CV-score per se is not mandatory for an association of SH with IHD. However, the association is multifactorial.

Effect of Low-Intensity Pulsed Ultrasound on Ischaemic Heart Disease Patients (Novel Technique)

Ischaemic Heart Disease (IHD) or Coronary heart disease means that the heart is not getting enough blood and oxygen supply through the coronary arteries. The most common cause of this disease is the process of atherosclerosis in the coronary arteries. Although significant progress has been made in the management of ischaemic heart disease (IHD) The number of severe IHD patients is increasing. The treatment options for IHD have not changed much over the last three decades, which is divided between medications, coronary Angioplasty and Coronary artery bypass surgery. Thus it was crucial to develop new, non-invasive therapeutic strategies in case of Failure of medical or interventional therapy or in case patient is not fit for surgery or angioplasty. In this study, we are pleased to reveal a novel technique that was carried out on a human model. We aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of patients with Ischaemic Heart Disease. We have set up the inclusion and exclusion criteria, the treatment protocol of LIPUS on IHD patients. In this limited group of IHD patients, We found promising clinical results and improvement on myocardial functions.

Transcaval approach to treat a type II endoleak

An 87-year-old man had an elective endovascular aneurysm repair in 2015 (Endurant; Medtronic, Santa Rosa, Calif). A type II endoleak from the inferior mesenteric artery (IMA) was noticed in the first surveillance scan. All subsequent ultrasound scans showed the endoleak with a stable sac (A). He has severe obstructive pulmonary disease and ischemic heart disease (American Society of Anesthesiologists class 3) while leading an independent life. In 2019, although he was asymptomatic, sac size grew by 1 cm.

Therapeutic Angiogenesis with Sound Waves.

Along with the progress of global aging, the prognosis of severe ischemic heart disease (IHD) remains poor, and thus the development of effective angiogenic therapy remains an important clinical unmet need. We have developed low-energy extracorporeal cardiac shock wave therapy as an innovative minimally invasive angiogenic therapy and confirmed its efficacy in a porcine chronic myocardial ischemia model in animal experiments as well as in patients with refractory angina. Since ultrasound is more advantageous for clinical application than shock waves, we then aimed to develop ultrasound therapy for IHD. We demonstrated that specific conditions of low-intensity pulsed ultrasound (LIPUS) therapy improve myocardial ischemia in animal models through the enhancement of angiogenesis mediated by endothelial mechanotransduction. To examine the effectiveness of our LIPUS therapy in patients with severe angina pectoris, we are now conducting a prospective multicenter clinical trial in Japan. Furthermore, to overcome the current serious situation of dementia pandemic but with no effective treatments worldwide, we have recently demonstrated that our LIPUS therapy also improves cognitive impairment in mouse models of Alzheimer’s disease and vascular dementia. Here, we summarize the progress in our studies to develop angiogenic therapies with sound waves.

The Hole of Hope: Balloon Atrial Septostomy for Left Ventricle Unloading during VA ECMO

Veno arterial extracorporeal membrane oxygenation (VA-ECMO) is an established rescue therapy for cardiogenic shock (CS). However, the increase in left ventricle (LV) afterload associated with inappropriate LV unloading remains an unsolved problem. Balloon atrial septostomy (BAS) is an inexpensive effective with low complication rates. Our purpose was to understand BAS effect in this setting. Observational retrospective study, including patients submitted to BAS for LV unloading during VA-ECMO support due to CS between 2018 and 2019. Inotropic use was evaluated by the Wernovsky inotropic score. Statistical analysis was performed by median comparison with Wilcoxon test for related samples. Four patients with refractory CS despite VA-ECMO and intra aortic balloon pump (n=3) or Impella (n=1) support were included. The age of the patients was 55.5 years (IQR 46.8-64.3) and 75% were male. The basal median LV ejection fraction was 29.5%. All had severe functional mitral regurgitation and ischemic heart disease (n=3) or severe aortic stenosis (n=1). BAS was performed after a median time of 8 days (IQR 5.5-12.0) after ECMO with a final dimension of 5 mm. The reduction in left atrial pressure led to resolution of pulmonary edema in all patients. There was a hemodynamic improvement after the procedure, with lower inotropic use in 75% of patients (median difference -0,6; p= 1.00), and reduction in pulmonary pressures and lactate levels (Table 1). Additionally we documented an increase in LV outflow tract (LVOT) velocity time integral (VTI) and in the PaO2/FiO2 ratio. After a follow-up of 25.5 days (IQR 12.8-45.8) half of the patients were weaned from VA-ECMO or transplanted. One procedure was complicated by a femoral hematoma. Percutaneous BAS is a simple and effective procedure to treat refractory pulmonary edema during VA-ECMO support. The improvement in LV performance, documented by the increase in LVOT VTI, is likely due to improvement in intracavitary pressures and a better oxygenation.

CD271+ Human Mesenchymal Stem Cells Show Antiarrhythmic Effects in a Novel Murine Infarction Model.

Background: Ventricular arrhythmias (VA) are a common cause of sudden death after myocardial infarction (MI). Therefore, developing new therapeutic methods for the prevention and treatment of VA is of prime importance. Methods: Human bone marrow derived CD271+ mesenchymal stem cells (MSC) were tested for their antiarrhythmic effect. This was done through the development of a novel mouse model using an immunocompromised Rag2−/− γc−/− mouse strain subjected to myocardial “infarction-reinfarction”. The mice underwent a first ischemia-reperfusion through the left anterior descending (LAD) artery closure for 45 min with a subsequent second permanent LAD ligation after seven days from the first infarct. Results: This mouse model induced various types of VA detected with continuous electrocardiogram (ECG) monitoring via implanted telemetry device. The immediate intramyocardial delivery of CD271+ MSC after the first MI significantly reduced VA induced after the second MI. Conclusions: In addition to the clinical relevance, more closely reflecting patients who suffer from severe ischemic heart disease and related arrhythmias, our new mouse model bearing reinfarction warrants the time required for stem cell engraftment and for the first time enables us to analyze and verify significant antiarrhythmic effects of human CD271+ stem cells in vivo.

Aspects of Heart Failure in Patients with Ischemic Heart Disease after Percutaneous Coronary Revascularization with Polymer-coated Drug-Eluting Stents versus Bare-Metal Stents

Percutaneous coronary revascularization (PCR) with polymer-coated drug-eluting stents (DES) or bare-metal stents (BMS) is considered the standard therapy in advanced ischemic heart disease (IHD). Despite revascularisation, many of these patients subsequently develop heart failure with reduced ejection fraction (HFrEF). We analysed 51 patients with IHD, treated by PCR and insertion of DES and/or BMS who later developed HFrEF. Patients with DES where more likely women, of younger age and a higher incidence of diabetes mellitus compared to patients with BMS who were generally men, of older age and had more frequently acute ST-elevation myocardial infarction (STEMI) as indication for PCR. Although patients with DES had more severe IHD, their EF was higher, possibly due to the benefits offered by the DES.

Nanomedicine for Gene Delivery for the Treatment of Cardiovascular Diseases.

Background:Myocardial infarction (MI) is the most severe ischemic heart disease and di-rectly leads to heart failure till death. Target molecules have been identified in the event of MI including increasing angiogenesis, promoting cardiomyocyte survival, improving heart function and restraining inflammation and myocyte activation and subsequent fibrosis. All of which are substantial in cardiomy-ocyte protection and preservation of cardiac function.Methodology:To modulate target molecule expression, virus and non-virus-mediated gene transfer have been investigated. Despite successful in animal models of MI, virus-mediated gene transfer is hampered by poor targeting efficiency, low packaging capacity for large DNA sequences, immunogenicity induced by virus and random integration into the human genome.Discussion:Nanoparticles could be synthesized and equipped on purpose for large-scale production. They are relatively small in size and do not incorporate into the genome. They could carry DNA and drug within the same transfer. All of these properties make them an alternative strategy for gene transfer. In the review, we first introduce the pathological progression of MI. After concise discussion on the current status of virus-mediated gene therapy in treating MI, we overview the history and development of nanoparticle-based gene delivery system. We point out the limitations and future perspective in the field of nanoparticle vehicle.Conclusion:Ultimately, we hope that this review could help to better understand how far we are with nanoparticle-facilitated gene transfer strategy and what obstacles we need to solve for utilization of na-nomedicine in the treatment of MI.