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Introduction: Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening disease, defined as idiopathic cardiomyopathy occurring towards the end of pregnancy or in the months following delivery, abortion or miscarriage. We aim to raise awareness of this condition and give an overview of current knowledge as well as an insight and comparison of clinical trials focusing on randomized controlled trials. Material and methods: Systematic literature searches were conducted using PubMed up to December 2021. Studies published involving clinical trials and interventions in women with PPCM after 1970 were selected. Results: Randomized controlled trials have shown that addition of Bromocriptine to standardized heart failure therapy improves outcome in terms of recovery of left ventricular ejection fraction (LVEF), symptoms and death. Bromocriptine 2.5 mg twice daily for two weeks followed by 2.5 mg once daily for six weeks had the best trend anAddition of Levosimendan to standardized heart failure therapy had no effect, whereas addition of Selenium had an improvement in heart failure symptoms but did not reduce risk in terms of unrecovered LVEF or death. One prospective study showed a potential usage of TNF-alfa inhibitors, but was never tried in a randomized clinical trial.d outcome. Conclusion: PPCM is a rare and potentially fatal disease. New insights in pathophysiology, genetics and clinical studies, particularly randomized controlled trials have shown that addition of Bromocriptine has a beneficial effect in terms of improved LVEF and death. However, some clinical studies have shown promising results using anti-inflammatory pharmacological agents with an improvement in LVEF. We suggest that targeting an anti-inflammatory route may prove beneficial in patients with PPCM. However, further research is highly warranted.

AIMS The study assessed 4-year outcomes of intramyocardial injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in patients with ischaemic heart failure. METHODS AND RESULTS The MSC-HF trial was a randomized, double-blind, placebo-controlled trial. Patients were randomized 2:1 to intramyocardial injections of MSCs or placebo. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured by magnetic resonance imaging or computed tomography. Sixty patients aged 30-80 years with ischaemic heart failure, New York Heart Association class II-III, left ventricular ejection fraction (LVEF)

Atherosclerosis of coronary arteries can result in a hypoxic state where myocardial cells may become dysfunctional or die. The oxygen sensing transcription factor hypoxia inducible factor 1 responds to low oxygen levels by elevating the production of angiogenic growth factors, such as vascular endothelial growth factor (VEGF). Despite this, endogenous processes and conventional therapies are inefficient in some patients. To stimulate angiogenesis, VEGF has been injected into the myocardium. As stated in this review, this therapy has so far been proven safe and studies are conducted in several countries, including Denmark.

Background: Recurrent episodes of isolated pericardial effusion due to tuberculosis, leading to reduced Left Ventricle Ejection Fraction (LVEF), are uncommon. Methods: This is a case report of a previously healthy 32-years old male with tuberculous induced pericardial effusion as isolated manifestation. The only known exposure of tuberculosis was a brother with whom the patient did not have physical contact during the last year. The pericardial effusion repeatedly appeared after being drained a total of three times. Due to recurrent episodes of pericardial effusion, severe thickening of the pericardium, pericardial adherences and increasing affection on the heart, pericardiectomy was ultimately performed. Results: Biochemical examination, chest X-ray, computed tomography of thorax and abdomen and cytology report did not reveal any signs of malignancy, connective tissue disease or other infections including extra-pulmonary/pulmonary tuberculosis. However, the pericardial biopsy was Polymerase Chain Reaction positive (PCR) for tuberculosis DNA and showed granulomatous inflammation with necrosis. After 6 months anti-tuberculous therapy, biochemical parameters, LVEF and the clinical condition of the patient were normalized. Conclusion: Tuberculosis can be difficult to diagnose when it only manifests as pericardial effusion especially if the time for exposure is long before the appearance of symptoms and admission.

Background Improvements in medical and interventional therapies have transformed ischemic heart disease into a chronic illness for lot of patients. The disease is in progress and by time patients suffer from cardiac symptoms, reduced work capacity and decline in quality of life. Stem cell therapy is investigated as a treatment option for these patients. Purpose In this study, long-term safety and efficacy of autologous intra-myocardial injections of adipose-derived stromal cells (ASCs) were studied in patients with refractory angina. Methods Sixty patients were double-blinded 2:1 randomised to ASC or saline injections and followed for three years. The patients had significant angina due to ≥1 coronary artery stenosis but preserved left ventricular ejection fraction. ASCs were obtained from abdomen, ex vivo culture expanded and VEGF-A165 stimulated before delivery into the ischemic myocardium. Results The cardiac symptoms, CCS and NYHA classification, were significantly reduced in the ASC group during the three years follow-up period (2.5±0.9 to 1.8±1.2, P=0.002 and 2.4±0.6 to 2.2±0.8, P=0.007, respectively). However, no significant change was observed in CCS or NYHA in the placebo group during the follow-up period (2.5±0.8 to 2.1±1.3, P=0.186 and 2.7±0.6 to 2.4±0.8, P=0.314, respectively). Moreover, the number of weekly angina attacks reported was significantly reduced in the ASC group (P=0.017), but not in the placebo group (P=0.425). For patients in the ASC group, the bicycle exercise time (383±30s to 370±44s, P=0.052) and the exercise performance in watt were un-changed (81±6 to 78±10, P=0.123), but the performance in METs was reduced significantly (4.2±0.3 to 4.0±0.4, P=0.027) during the follow-up period. At the same time in the placebo group, there was a significant decline in bicycle exercise time (437±53s to 383±58s, P=0.001), the exercise performance measured in watt (87±12 watt to 80±12 watt, P=0.019) and in METs (4.5±0.4 to 4.1±0.4, P=0.002). In both groups, significant improved quality-of-life, angina stability, angina frequency and physical limitation score was observed but not for overall satisfaction score. Conclusion Patients receiving ASCs had improved cardiac symptoms during the three years follow-up period, which was not the case for patients in the placebo group. Moreover, patients receiving ASCs had unchanged exercise capacity, in opposition to deterioration in the placebo group. Acknowledgement/Funding Arvid Nilssons Foundation; Rigshospitalets Research Foundation; Aase and Ejnar Danielsens Foundation

Coronary microvascular dysfunction (CMD) is associated with a poor prognosis even in absence of obstructive coronary artery disease. CMD can be assessed as a myocardial blood flow reserve by positron emission tomography (PETMBFR) and as coronary flow velocity reserve by transthoracic Doppler echocardiography (TTDECFVR). Impaired first-pass perfusion assessed by cardiac magnetic resonance (CMR) is an early sign of ischemia. We aimed to investigate the association between CMD and CMR first-pass perfusion. Women (n = 66) with angina pectoris and an invasive coronary angiogram (

Summary Introduction Computed tomography (CT) is a novel method for assessment of myocardial perfusion and has not yet been compared to rubidium-82 positron emission tomography (PET). We aimed to compare CT measured semi-quantitative myocardial perfusion with absolute quantified myocardial perfusion using PET and to detect stenotic territories in patients with severe coronary artery disease. Materials and methods Eighteen patients with stenosis narrowing coronary arteries ≥70% demonstrated on invasive coronary angiography underwent rest and adenosine stress imaging obtained by 320-multidetector CT scanner and CT/PET 64-slice scanner. CT measured myocardial attenuation density (AD) and perfusion index (PI) were correlated to absolute PET myocardial perfusion values. Results Rest AD, rest and stress PI did not correlate to PET findings (r = 0·412, P = 0·113; r = 0·300, P = 0·259; and r = 0·508, P = 0·064, respectively). However, there was a significant correlation between stress AD and stress PET values (r = 0·670, P = 0·009) and between stress and rest differences for AD and PI with PET differences (r = 0·620, P = 0·006; and r = 0·639, P = 0·004, respectively). Furthermore, significant differences were observed between remote and stenotic territories for rest and stress AD (48 ± 14HU and 37 ± 16HU, P = 0·002; 76 ± 19HU and 58 ± 13HU, P

Recently, focus has changed from anatomical assessment of coronary arteries towards functional testing to evaluate the effect of stenosis on the myocardium before intervention. Besides positron-emission tomography (PET), cardiac MRI (CMR), and cardiac CT are able to measure myocardial perfusion. Myocardial perfusion abnormalities are the first sign of the ischaemic cascade in the development of coronary artery disease (CAD). PET is considered the non-invasive clinical reference standard for absolute quantification of myocardial perfusion. The diagnostic and prognostic value of PET is well-known and is used in routine clinical practice. However, PET uses radioactive tracers and has a lower spatial resolution compared to CMR and CT. CMR and CT are emerging techniques in the field of myocardial perfusion imaging. CMR uses magnetic resonance to obtain images, whereas CT uses x-rays during first-pass of non-ionic and ionic contrast agents, respectively. Absolute quantification with CMR has yet to be established in routine clinical practice, while CT has yet to prove its diagnostic and prognostic value. The upcoming years may change the way we diagnose and treat patients suspected of having CAD with more precise methods for measuring myocardial perfusion. The aim of this comprehensive review is to discuss current and emerging imaging techniques used for myocardial perfusion imaging.

Aims Regenerative treatment with mesenchymal stromal cells (MSCs) has been promising in patients with ischaemic heart failure but needs confirmation in larger randomized trials. We aimed to study effects of intra-myocardial autologous bone marrow-derived MSC treatment in patients with severe ischaemic heart failure. Methods and results The MSC-HF trial is a randomized, double-blind, placebo-controlled trial. Patients were randomized 2 : 1 to intra-myocardial injections of MSC or placebo, respectively. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured by magnetic resonance imaging or computed tomography at 6 months follow-up. Sixty patients aged 30–80 years with severe ischaemic heart failure, New York Heart Association (NYHA) classes II–III, left ventricular ejection fraction (LVEF)

To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI). There is a wide variability in the platelet reactivity to clopidogrel and HTPR has been associated with a poor prognosis.In this observational study, 923 consecutive patients without ST-elevation myocardial infarction (STEMI) and adequately pre-treated with clopidogrel were screened for HTPR with multiple electrode aggregometry after assessment of the coronary anatomy. Patients were grouped based on their response to clopidogrel and the assigned antiplatelet strategy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or stent thrombosis.HTPR was demonstrated in 237 patients (25.7%). Of these, 114 continued on conventional clopidogrel therapy, while the remaining 123 received intensified antiplatelet therapy with either double-dose clopidogrel (150 mg daily, n = 55) or the newer P2Y12-inhibitors, prasugrel or ticagrelor (n = 68) for at least 30 days after the index procedure. The median follow-up was 571 days (interquartile range, 373-746). Intensifying antiplatelet therapy reduced the rate of the composite endpoint (p0.001). After adjustment for potential confounders, HTPR in combination with conventional clopidogrel therapy remained independently associated with an increased risk of cardiovascular events (hazard ratio (HR), 2.92; 95% CI, 1.90-4.48), whereas intensified treatment reduced the risk to a level equivalent to that of patients exhibiting normal platelet reactivity (HR, 1.08; 95% CI, 0.59-1.99).Tailored antiplatelet therapy significantly reduced the event rate in patients exhibiting HTPR prior to PCI.

Aim was to compare absolute myocardial perfusion using cardiac magnetic resonance imaging (CMRI) based on Tikhonov's procedure of deconvolution and rubidium-82 positron emission tomography (Rb-82 PET).Fourteen patients with coronary artery stenosis underwent rest and adenosine stress imaging by 1.5-Tesla MR Scanner and a mCT/PET 64-slice Scanner. CMRI were analyzed based on Tikhonov's procedure of deconvolution without specifying an explicit compartment model using our own software. PET images were analyzed using standard clinical software. CMRI and PET data was compared with Spearman's rho and Bland-Altman analysis.CMRI results were strongly and significantly correlated with PET results for the absolute global myocardial perfusion differences (r=0.805, p=0.001) and for global myocardial perfusion reserve (MPR) (r=0.886, p0.001). At vessel territorial level, CMRI results were also significantly correlated with absolute PET myocardial perfusion differences (r=0.737, p0.001) and MPR (r=0.818, p0.001). Each vessel territory had similar strong correlation for absolute myocardial perfusion differences (right coronary artery (RCA): r=0.787, p=0.001; left anterior descending artery (LAD): r=0.796, p=0.001; left circumflex artery (LCX): r=0.880, p0.001) and for MPR (RCA: r=0.895, p0.001; LAD: r=0.886, p0.001; LCX: r=0.886, p0.001).On a global and vessel territorial basis, CMRI-measured absolute myocardial perfusion differences and MPR were strongly and significantly correlated with the Rb-82 PET findings.

High on-treatment platelet reactivity (HTPR) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). The antiplatelet effect and safety of prasugrel was compared to that of double-dose clopidogrel in patients with stable coronary artery disease or acute coronary syndrome (ACS) exhibiting HTPR on clopidogrel and treated with PCI, using multiple electrode aggregometry (MEA) to assess platelet reactivity. Of 923 patients screened, 237 (25.7%) exhibited HTPR. Of these, 106 were eligible for participation in a randomized trial comparing two intensified antiplatelet regimen: 52 were assigned to double maintenance-dose clopidogrel and 54 to standard-dose prasugrel. At 1 month, tailoring antiplatelet therapy improved platelet inhibition to a level considered as therapeutic in 73.1% of patients. Prasugrel entailed greater platelet inhibition (p = 0.02) and a lower rate of persisting HTPR at follow-up compared to double-dose clopidogrel (HTPR persisted in 20.4% and 42% respectively, p = 0.02). Within the 30-day follow-up, no major bleeds were observed and the incidence of major adverse cardiovascular events (MACE) was similar in the two treatment arms. Prasugrel demonstrated superiority to double-dose clopidogrel in overcoming HTPR and reducing platelet activity. Intensifying antiplatelet therapy in both ACS and stable angina pectoris (SAP) patients exhibiting HTPR prior to PCI was well tolerated.

Number of stromal cells injected in patients with ischaemic heart disease (IHD) may be of importance for the treatment efficacy, which in turn may be influenced by various patient-related factors. In this study, we investigate whether patient-related factors influence the number of autologous stromal cells reached after in vitro culture expansion for clinical therapy.Culture expansion data from 111 patients with IHD treated with autologous stromal cells in three clinical trials were used. We correlated the final cell count after two passages of cultivation with different patient factors.There was a significant relation between body mass index (BMI) and the number of adipose derived stromal cells (ASCs) reached after culture expansion and for all patients included into the three studies (r = 0.375, p = .019 and r = 0.200, p = .036, respectively). Moreover, there was a significantly higher number of ASCs reached in patients with hypertension compared to those without hypertension and for all patients overall (68.8 ± 39.6 × 10Patient related factors such as BMI, hypertension and gender may influence the number of MSCs reached after in vitro culture expansion.

Although, treatment of ischemic heart disease (IHD) has improved considerably within the last decades, it is still the main cause of death worldwide. Despite maximum treatment, many IHD patients suffer from refractory angina and heart failure, which severely limits their daily lives. Moreover, IHD is very costly for the health care system. Therefore, new treatment options and strategies are being researched intensely. Stem cell therapy to improve myocardial perfusion and stimulate growth of new cardiomyocytes could be a new way to go. Nevertheless, the results from clinical studies have varied considerably, probably due to the use of many different cell lines obtained from different tissues and the different patient populations. The present review will focus on treatment with the mesenchymal stromal cell from bone marrow and adipose tissue in animal and patients with acute and chronic IHD (CIHD).

INTRODUCTION: The legitimacy of Mawlid-un-Nabi is oftened questioned,since Mawlid is not expressly mentioned in the Quran or Hadiths.The aims of the article is to evaluate ligitimacy of celebrating the bith of Prophet Muhammad(P.B.U.H). METHOD: We have evaluated the legitimacy of celebrating Mawlid-un- Nabi based on reference from the Quran. Sahih Al Bukhari and Sahih Muslim by first looking at the basic principle of islamic jurisprudence(fiqh). Secondly the article evaluates the meaning of Prophet(P.B.U.H).birth according to islam. Finally this article discusses the birth and value of Prophet Muhammad (P.B.U.H). Based on the concept of celebration in general and the value of celebration of islam. RESULT: The birth of Prophet(P.B.U.H) are specific mentioned as special days in the Quran(Maryam 19:15, Maryam 19:33) and the birthday of Prophet Muhammad(P.B.U.H). is thereby also a special day(dalalah-al-nass). Special days are encouraged by Allah almighty to be celebrated(mutlaq command)(Yonus 10:58, As-Duha 93:11). The Prophet MuhammadP.B.U.H) imself celebrated his birthday(Sahih Muslim. book 6, chapter 33, Hadith number 2603) and the Companions (Allah be placed with them) Of the Prophet Muhammad(P.B.U.H) used to gather in remembrnace of Allah almighty and tell story about yhe life

The aim was to compare absolute quantified myocardial perfusion (MP) to semi-quantitative measurements of MP using MRI for detection of ischemia. Twenty-nine patients underwent rest and stress MP imaging obtained by 1.5T MRI and analyzed using own developed software and by commercial available software. Linear regression analysis demonstrated that absolute quantitative data correlated stronger to maxSI (rest: r=0.296, p=.193; stress: r=0.583, p=0.011; myocardial perfusion reserve (MPR): r=0.789, p

Since the introduction of percutaneous coronary intervention for coronary artery disease, thousands of patients have been treated with the implantation of coronary stents. Moreover, several of the patients with coronary stent undergo cardiac magnetic resonance (CMR) imaging every year. This case report is of a 77-year-old man who was previously treated with the implantation of a coronary stent in the left circumflex artery. He underwent CMR imaging, which revealed a process 14×21 mm in the left atrium. Cardiac contrast computed tomography did not demonstrate any cardiac pathology. While the signal loss on MRI associated with implanted metallic devices is known, we report a case where an implanted coronary stent in the left circumflex artery led to an intracardiac signal loss mimicking intracardiac thrombus/tumor.

Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants in the Copenhagen General Population Study (CGPS), of which 991 and 1,693 participants, respectively, had developed myocardial infarction (MI) by August 2010. Participants in the CCHS were genotyped for all six variants identified by resequencing lecithin-cholesterol acyltransferase in 380 individuals. One variant, S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies combined was 0.49 (0.11–2.16), whereas the hazard ratio for MI for a 50% reduction in plasma HDL cholesterol in the CCHS was 2.11 (1.70–2.62) (Pcomparison = 0.03).Conclusion:Low plasma HDL cholesterol levels robustly associated with increased risk of MI but genetically decreased HDL cholesterol did not. This may suggest that low HDL cholesterol levels per se do not cause MI.

Background Stem cell therapy is an emerging treatment modality in cardiovascular disease. The best cell type and delivery method in different cardiovascular diseases remain to be determined. Study Design The MSC-HF trial is a phase 2, single-center, double-blind, randomized, placebo-controlled trial of intramyocardial delivery of autologous bone-marrow derived mesenchymal stromal cells (MSCs) in patients with chronic ischemic heart failure. A total of 60 patients will be randomized in a 2:1 pattern to receive intramyocardial injections of either MSCs or placebo. Patients will be followed up for 12 months. Methods Bone marrow will be obtained by aspiration from the iliac crest. Mesenchymal stromal cells will be isolated, and culture will be expanded for 6 to 8 weeks. A total of 12 to 15 MSC or placebo injections will be placed in an ischemic viable region of the myocardium using the electromechanical NOGA-XP system (Biologics Delivery Systems Group, Johnson & Johnson, Irwindale, CA). Endpoints The primary endpoint is change in left ventricle end-systolic volume, measured by magnetic resonance imaging (MRI) or computed tomography (CT) at 6-month follow-up. Secondary endpoints are left ventricle ejection fraction, ventricular volumes, wall thickness, and systolic wall thickening measured by MRI or CT in addition to measurement of myocardial scar tissue by MRI. Other secondary endpoints are safety of treatment, clinical symptoms and functional capacity, weekly angina attacks, use of short-term nitroglycerine, and quality of life. Conclusion A randomized, double-blind, placebo-controlled, clinical trial of intramyocardial delivery of MSCs in patients with ischemic heart failure has been set up to confirm the positive findings in open-labeled clinical trials.

The present Cochrane review included 23 studies randomized placebo-controlled clinical trials with a total of 1,255 patients. The effect of autologous cell therapy versus placebo was examined on left ventricular ejection fraction (LVEF), adverse effects and mortality in patients with chronic ischaemic heart disease. Patients treated with cell therapy had improved LVEF and functional status compared to patients who received placebo. There were no cell-related and only few procedure-related side effects. A positive effect of cell therapy on long-term survival was also demonstrated.

Diabetes mellitus is a well-known risk factor for coronary artery disease (CAD), which can lead to acute myocardial infarction, chronic myocardial ischaemia and heart failure. Despite the advantages in medical treatment, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), morbidity and mortality is still high in patients with CAD. Along with PCI and CABG or in patients without options for revascularization, stem cell regenerative therapy in controlled trials is a possibility. Stem cells are believed to exert their actions by angiogenesis and regeneration of cardiomyocytes. Recently published clinical trials and meta-analysis of stem cell studies have shown encouraging results with increased left ventricle ejection fraction and reduced symptoms in patients with CAD and heart failure. There is some evidence of mesenchymal stem cell being more effective compared to other cell types and cell therapy may be more effective in patients with known diabetes mellitus. However, further investigations are warranted.

The clinical consequence of the increasing incidence of coronary artery disease is a growing problem worldwide and ischemic heart disease remains the most common cause of death and a major cause of hospital admissions in industrialised countries. Early treatment with stabilizing drugs and mechanical revascularization by percutaneous coronary intervention or coronary by-pass surgery has reduced the mortality significantly. However, there is still a group of patients, which cannot be treated satisfactorily with these interventions. Treatment with genes encoding vascular growth factors or stem cells with the potential to regenerate the damaged myocardium is a relatively new approach. The results from early clinical studies on gene and stem cell therapy for cardiac regeneration in patients with acute or chronic ischemic heart disease have been inconsistent. Some of the discrepancy could be due to differences in study designs or patient selection. This review will present the conducted clinical trials and try to clarify the influence of patient selection, chosen cell type, cell source, delivery methods and mechanisms of action on the differences in results.

The challenge for therapies targeting perfusion abnormalities is to identify and evaluate the region of interest. The aim of this study was to compare rest and stress myocardial perfusion measured by cardiac multi-detector computed tomography (MDCT) and cardiac magnetic resonance (CMR) imaging in patients with invasive coronary angiography demonstrated occluded vessels. Twenty-four patients with refractory angina due to occluded coronary arteries underwent perfusion imaging obtained by 320-MDCT scanner and 1.5 T MR scanner. Rest and adenosine stress images were obtained and interpreted using the modified 17-segment American Heart Association model. For the qualitative analysis, each segment was graded according to the following scoring system: 0 = no defect, 1 = hypoperfusion transmural extent1/3, 2 = 1/3-1/2, 3 =1/2, and 4 = infarct stigmata. In the semiquantitative analysis the perfusion was either scored 0 (normal) or 1 (abnormal). The summed rest and stress scores were calculated. MDCT and CMR had a high probability to identify perfusion defects. An excellent correlation between MDCT and CMR summed rest (r = 0.916) and stress scores (r = 0.915) was found. The interobserver reproducibility was high for MDCT and CMR images. The qualitative and semiquantitative MDCT against CMR analysis of rest and stress images showed high concordance to detect perfusion defects per vascular territory and on a per myocardial segment basis. 320-MDCT and CMR perfusion imaging can be used clinically to identify myocardial perfusion defects and potentially evaluate the effect of therapy targeting perfusion abnormalities.

Adipose tissue represents an abundant, accessible source of multipotent adipose-derived stromal cells (ADSCs). Animal studies have suggested that ADSCs have the potential to differentiate in vivo into endothelial cells and cardiomyocytes. This makes ADSCs a promising new cell source for regenerative therapy to replace injured tissue by creating new blood vessels and cardiomyocytes in patients with chronic ischemic heart disease. The aim of this special report is to review the present preclinical data leading to clinical stem cell therapy using ADSCs in patients with ischemic heart disease. In addition, we give an introduction to the first-in-man clinical trial, MyStromalCell Trial, which is a prospective, randomized, double-blind, placebo-controlled study using culture-expanded ADSCs obtained from adipose-derived cells from abdominal adipose tissue and stimulated with VEGF-A165 the week before treatment.

The present first-in-human clinical trial evaluated the safety and feasibility of a newly developed and cryopreserved Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors for intramyocardial injection in ten patients with ischemic heart disease and ischemic heart failure (IHF). Batches of CSCC_ASC were isolated from three healthy donors by liposuction from abdominal adipose tissue. Adipose mesenchymal stromal cells were culture expanded in bioreactors without the use of animal constituents, cryopreserved, and stored in vials in nitrogen dry-storage containers until use. Direct injection of CSCC_ASC into the myocardium did not cause any complications or serious adverse events related to either treatment or cell administration in a 6-month follow-up period. Four out of ten heart failure patients developed donor-specific de novo human leukocyte antigen (HLA) class I antibodies, and two out of ten patients had donor-specific HLA antibodies already at baseline. There were no clinical symptoms or changes in inflammatory parameters in the follow-up period that indicated an ongoing immune response. There was a tendency toward improvement in cardiac function after CSCC_ASC treatment at 6-month follow-up: left ventricular end systolic volume decreased and left ventricular ejection fraction increased. In addition, exercise capacity increased. These changes were independent of the presence or absence of HLA antibodies. It is concluded that the newly developed cryopreserved product CSCC_ASC from healthy donors was a safe and feasible treatment. We observed a tendency toward efficacy in patients with IHF. These findings have to be confirmed in larger placebo controlled clinical trials.

Even in absence of obstructive coronary artery disease women with angina pectoris have a poor prognosis possibly due to coronary microvascular disease. Coronary microvascular disease can be assessed by transthoracic Doppler echocardiography measuring coronary flow velocity reserve (CFVR) and by positron emission tomography measuring myocardial blood flow reserve (MBFR). Diffuse myocardial fibrosis can be assessed by cardiovascular magnetic resonance (CMR) T1 mapping. We hypothesized that coronary microvascular disease is associated with diffuse myocardial fibrosis. Women with angina, a clinically indicated coronary angiogram with