Increased [18F]FDG uptake in the infarcted myocardial area displayed by combined PET/CMR correlates with snRNA-seq-detected inflammatory cell invasion.

Combined [18F]FDG PET-cardiac MRI imaging (PET/CMR) is a useful tool to assess myocardial viability and cardiac function in patients with acute myocardial infarction (AMI). Here, we evaluated the prognostic value of PET/CMR in a porcine closed-chest reperfused AMI (rAMI) model. Late gadolinium enhancement by PET/CMR imaging displayed tracer uptake defect at the infarction site by 3 days after the rAMI in the majority of the animals (group Match, n = 28). Increased [18F]FDG uptake at the infarcted area (metabolism/contractility mismatch) with reduced tracer uptake in the remote viable myocardium (group Mismatch, n = 12) 3 days after rAMI was observed in the animals with larger infarct size and worse left ventricular ejection fraction (LVEF) (34 ± 8.7 vs 42.0 ± 5.2%), with lower LVEF also at the 1-month follow-up (35.8 ± 9.5 vs 43.0 ± 6.3%). Transcriptome analyses by bulk and single-nuclei RNA sequencing of the infarcted myocardium and border zones (n = 3 of each group, and 3 sham-operated controls) revealed a strong inflammatory response with infiltration of monocytes and macrophages in the infarcted and border areas in Mismatch animals. Our data indicate a high prognostic relevance of combined PET/MRI in the subacute phase of rAMI for subsequent impairment of heart function and underline the adverse effects of an excessive activation of the innate immune system in the initial phase after rAMI.

Detection of sympathetic denervation defects in Fabry disease by hybrid [11C]meta-hydroxyephedrine positron emission tomography and cardiac magnetic resonance.

BACKGROUND: Myocardial glycosphingolipid accumulation in patients with Fabry disease (FD) causes biochemical and structural changes. This study aimed to investigate sympathetic innervation in FD using hybrid cardiac positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS AND RESULTS: Patients with different stages of Fabry disease were prospectively enrolled to undergo routine CMR at 1.5T, followed by 3T hybrid cardiac PET/MRI with [11C]meta-hydroxyephedrine ([11C]mHED). Fourteen patients with either no evidence of cardiac involvement (n = 5), evidence of left ventricular hypertrophy (LVH) (n = 3), or evidence of LVH and fibrosis via late gadolinium enhancement (LGE) (n = 6) were analyzed. Compared to patients without LVH, patients with LVH or LVH and LGE had lower median T1 relaxation times (ms) at 1.5 T (1007 vs. 889 vs. 941 ms, p = 0.003) and 3T (1290 vs. 1172 vs. 1184 p = .014). Myocardial denervation ([11C]mHED retention < 7%·min) was prevalent only in patients with fibrosis, where a total of 16 denervated segments was found in two patients. The respective area of denervation exceeded the area of LGE in both patients (24% vs. 36% and 4% vs. 32%). However, sympathetic innervation defects ([11C]mHED retention ≤ 9%·min) occurred in all study groups. Furthermore, a reduced sympathetic innervation correlated with an increased left ventricular mass (p = .034, rs = - 0.57) and a reduced global longitudinal strain (GLS) (p = 0.023, rs = - 0.6). CONCLUSION: Hybrid cardiac PET/MR with [11C]mHED revealed sympathetic innervation defects, accompanied by impaired GLS, in early stages of Fabry disease. However, denervation is only present in patients with advanced stages of FD showing fibrosis on CMR.

Long-term physical activity leads to a significant increase in serum sRAGE levels: a sign of decreased AGE-mediated inflammation due to physical activity?

There is growing evidence that low levels of the circulating soluble receptor of advanced glycation end products (sRAGE) are a valuable predictor of cardiovascular disease (CVD). The aim of this prospective study was to investigate the influence of long-term physical activity on serum sRAGE levels. 109 subjects were recruited, and 98 completed the study. Participants were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. sRAGE was measured at baseline and after 2/6/8 months by ELISA. Backwards, multiple linear regression analysis was performed to investigate the association of co-variables age, sex, BMI, and performance at baseline, HbA1c, and lipoprotein a with baseline sRAGE levels. We identified BMI and lipoprotein a as significant predictors for baseline sRAGE levels. Compared to subjects with a performance gain ≤ 4.9% subjects with a gain > 5% showed a significant increase in sRAGE levels up to 22%. sRAGE serum levels correlate negatively with lipoprotein a levels and BMI and long-term physical activity leads to a significant increase in serum sRAGE levels (9-22%), whereby the sRAGE increase is most pronounced in subjects with initially low-performance levels, suggesting that in particular, these subject profit the most from increased physical activity. The sport-mediated increase of sRAGE might be a sign of decreased AGE-mediated inflammation and highlight the protective effect of sports on CVD and other disease which are at least partly mediated by an increased inflammation status.Clinical trials registration NCT02097199.

Endurance training significantly increases serum endocan but not osteoprotegerin levels: a prospective observational study.

BACKGROUND: Endocan (EN) was suggested a potential inflammatory and cardiovascular disease (CVD) marker which might also be involved in renal failure and/or renal failure-associated vascular events. It is not clear whether osteoprotegerin (OPG) is a pro- or anti-atherogenic factor, however, it is agreed upon that OPG is elevated in subjects with increased calcification status. The aim of the study was to investigate the influence of long-term physical activity on serum endocan (EN) and osteoprotegerin-levels. METHODS: One hundred nine subjects were told to increase their amount of physical activity for 8 months by performing 150min/week moderate or 75min/week vigorous exercise. Incremental cycle ergometer tests were performed at the beginning and the end of the study to prove and quantify the performance gain. Blood samples were drawn at baseline and every 2 months for the determination of EN and OPG. To investigate the difference between baseline and 8 months levels of EN and OPG we used a paired sample t-test. To investigate the significance of the tendency of the progression (baseline/2 months/4 months/6 months/8 months) we used a Friedman test. RESULTS: Thirty-eight female and 60 male subjects completed the study. In the group of 61 subjects who had a performance gain by >4,9% EN-levels increased from 146 ± 110 to 196 ± 238 pg/ml (p = 0,036) equivalent to an increase of 33,5% but there was no significant change in OPG (4,4 ± 2,4 pmol/l vs. 4,3 ± 2,1 pmol/l; p = 0,668). CONCLUSIONS: Physical activity increases significantly EN-levels relativizing the status of EN as proinflammatory factor. EN should rather be considered as a mediator which is involved in several physiological (e.g., angiogenesis) but also pathological processes (e.g., CVD, tumour progression or endothelium-dependent inflammation) and whose expression can be significantly influenced by long term endurance training. TRIAL REGISTRATION: Clinical trial registration number: NCT02097199 Date of trial registration at Clinical Trials.gov: 24.03.2014; last update: 6.1.2016.

Sports and HDL-Quality Reflected By Serum Amyloid A and Surfactant Protein B.

Background: The aim of this prospective study was to investigate the influence of long-term physical activity on HDL quality, reflected by serum amyloid A (SAA) and surfactant protein B (SPB). Methods and results: 109 healthy subjects were recruited, 98 completed the study. Participants perform within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. SAA and SPB were measured at baseline and after 4 and 8 months by ELISA. In contrary to HDL-quantity, there was no sports-induced change in SAA or SPB observable. However, significant predictors for SPB-levels were smoking status, BMI and weekly alcohol consumption and for SAA weekly alcohol consumption together with sex and hsCRP-levels. Conclusions: Long-term physical activity increases HDL-quantity but has no impact on HDL-quality reflected by SAA and SPB. Smoking is associated with higher SPB-levels and the weekly alcohol intake is associated with both higher SAA and SPB-levels suggesting a damaging effect of smoking and drinking alcohol on the HDL-quality. We assume that HDL-quality is at least as important as HDL-quantity when investigating the role of HDL in (cardiovascular) disease and should receive attention in further studies dealing with HDL.

Long-term endurance training increases serum cathepsin S and decreases IL-6 and hsCRP levels.

Cathepsin S (CS) was shown to play a key role in cancer progression, atherosclerosis, heart valve disease, insulin resistance and diabetes mellitus. The present prospective study aimed to investigate the influence of sports on CS, interleukin-6 (Il-6) and high-sensitivity C-reactive protein (hsCRP) levels. Ninety-eight of 109 participants completed the study. Ergometries were performed at baseline and after 8 months to evaluate/quantify the performance gain. Blood samples were taken at baseline and every 2 months. CS was measured by ELISA (enzyme-linked immunosorbent assay). Compared to the control group (mean performance gain -3.41 ± 4.62%) we observed a significant physical-activity-induced increase of CS levels (3.45-3.73 ng · ml-1; P = 0.027) and a significant decrease of Il-6 (2.43-1.91 pg · ml-1; P = 0.031) and hsCRP-levels (0.11-0.09 mg · dl-1; P = 0.001) in the intervention group (mean performance gain: 12.13 ± 6.32%). Furthermore, the tendency of the progression was significant for CS and Il-6 (P = 0.002/0.033). We could show a significant sports-induced decrease of the classic inflammation parameters hsCRP/Il-6, probably expressing a downregulation of permanently prevalent inflammation processes. Simultaneously CS levels increased significantly. Our results show that increasing CS amounts are not simply to equal with an enhanced inflammation status and might even have beneficial effects on inflammation and angiogenesis.

Case report: Myocardial perfusion gated-SPECT in pulmonary artery hypertension-the Movahed's sign.

Primary pulmonary artery hypertension (PAH) is a clinical diagnosis that requires the exclusion of other underlying causes of pulmonary hypertension (PH). Increased pulmonary artery (PA) pressure and subsequent right ventricular (RV) pressure overload often result in a flattening of the curved interventricular septum, leading to a D-shaped left ventricle (LV), as observed in echocardiographic short-axis views. A similar finding may be also observed on myocardial perfusion SPECT images, the so-called Movahed's sign. We present a clinical case of a female patient with PAH and progression of exertional dyspnea that underwent myocardial perfusion SPECT to investigate LV myocardial ischemia. The SPECT images revealed enhanced tracer uptake in the dilated right ventricle. Additionally, we observed a D-shaped LV or Movahed's sign, which may serve as a potential marker of RV pressure overload, along with a small stress-induced perfusion defect on the LV septal wall. Our findings highlight the importance of considering the presence of a D-shaped LV and signs of RV pressure overload, as they can alter the interpretation of LV perfusion deficits on SPECT images. This case report aims to emphasize the complex nature of right heart abnormalities in pathologies such as PAH and the consideration of the RV implications in myocardial SPECT images-which typically focus solely on the LV.

Phenotyping of a novel COL4A4 and novel GLA variant in a patient presenting with microhematuria and mildly impaired kidney function: a case report.

We describe the case of a 44-year-old male patient with a longstanding history of microhematuria and mildly impaired kidney function (CKD G2A1). The family history disclosed three females who also had microhematuria. Genetic testing by whole exome sequencing revealed two novel variants in COL4A4 (NM_000092.5: c.1181G>T, NP_000083.3: p.Gly394Val, heterozygous, likely pathogenic; Alport syndrome, OMIM# 141200, 203780) and GLA (NM_000169.3: c.460A>G, NP_000160.1: p.Ile154Val, hemizygous, variant of uncertain significance; Fabry disease, OMIM# 301500), respectively. Extensive phenotyping revealed no biochemical or clinical evidence for the presence of Fabry disease. Thus, the GLA c.460A>G, p.Ile154Val, is to be classified as a benign variant, whereas the COL4A4 c.1181G>T, p.Gly394Val confirms the diagnosis of autosomal dominant Alport syndrome in this patient.

Long-Term Monitoring of Cardiac Involvement under Migalastat Treatment Using Magnetic Resonance Tomography in Fabry Disease.

Background: Fabry cardiomyopathy is characterized by left ventricular hypertrophy, myocardial fibrosis, arrhythmia, and premature death. Treatment with migalastat, an oral pharmacological chaperone, was associated with a stabilization of cardiac biomarkers and a reduction in left ventricular mass index, as measured by echocardiography. A recent study, using cardiac magnetic resonance (CMR) as the gold standard, found a stable course of myocardial involvement after 18 months of treatment with migalastat. Our study aimed to provide long-term CMR data for the treatment with migalastat. Methods: A total of 11 females and four males with pathogenic amenable GLA mutations were treated with migalastat and underwent 1.5T CMR imaging for routine treatment effect monitoring. The main outcome was a long-term myocardial structural change, reflected by CMR. Results: After migalastat treatment initiation, left ventricular mass index, end diastolic volume, interventricular septal thickness, posterior wall thickness, estimated glomerular filtration rate, and plasma lyso-Gb3 remained stable during the median follow-up time of 34 months (min.: 25; max.: 47). The T1 relaxation times, reflecting glycosphingolipid accumulation and subsequent processes up to fibrosis, fluctuated over the time without a clear trend. No new onset of late gadolinium enhancement (LGE) areas, reflecting local fibrosis or scar formation of the myocardium, could be detected. However, patients with initially present LGE showed an increase in LGE as a percentage of left ventricular mass. The median α-galactosidase A enzymatic activity increased from 37.3% (IQR 5.88-89.3) to 105% (IQR 37.2-177) of the lower limit of the respective reference level (p = 0.005). Conclusion: Our study confirms an overall stable course of LVMi in patients with FD, treated with migalastat. However, individual patients may experience disease progression, especially those who present with fibrosis of the myocardium already at the time of therapy initiation. Thus, a regular treatment re-evaluation including CMR is needed to provide the optimal management for each patient.

The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure.

PURPOSE: Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO(2)) in patients with chronic heart failure using (11)C-acetate positron emission tomography (PET). METHODS: We prospectively enrolled 21 patients with severe heart failure. (11)C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. RESULTS: Under resting conditions, the values of myocardial blood flow (MBF), MVO(2) and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 ± 0.18 ml min(-1) g(-1) with the device off and 0.80 ± 0.15 ml min(-1) g(-1) with the device on (p = 0.818), MVO(2) was 6.81 ± 1.69 ml/min/100 g with the device off and 7.15 ± 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 ± 1.14 mmHg ml/m(2) with the device off and 5.21 ± 1.36 mmHg ml/m(2) with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO(2) and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. CONCLUSION: These results indicate that CCM does not induce increased MVO(2), even under stress conditions.

Patient Selection and Clinical Indication for Chronic Total Occlusion Revascularization-A Workflow Focusing on Non-Invasive Cardiac Imaging.

Percutaneous coronary intervention of chronic total occlusion (CTO PCI) is a challenging procedure with high complication rates and, as not yet fully understood long-term clinical benefits. Ischemic symptom relief in patients with high ischemic burden is to date the only established clinical indication to undergo CTO PCI, supported by randomized controlled trials. In this context, current guidelines suggest attempting CTO PCI only in non-invasively assessed viable CTO correspondent myocardial territories, with large ischemic areas. Hence, besides a comprehensive coronary angiography lesion evaluation, the information derived from non-invasive cardiac imaging techniques is crucial to selecting candidates who may benefit from the revascularization of the occluded vessel. Currently, there are no clear recommendations for a non-invasive myocardial evaluation or choice of imaging modality pre-CTO PCI. Therefore, selecting among available options is left to the physician's discretion. As CTO PCI is strongly recommended to be carried out explicitly in experienced centers, full access to non-invasive imaging for risk-benefit assessment as well as a systematic institutional evaluation process has to be encouraged. In this framework, we opted to review the current myocardial imaging tools and their use for indicating a CTO PCI. Furthermore, based on our experience, we propose a cost-effective systematic approach for myocardial assessment to help guide clinical decision-making for patients presenting with chronic total occlusions.

RANTES and CD40L under Conditions of Long-Term Physical Exercise: A Potential Link to Adaptive Immunity.

Regular physical exercise was found to be associated with an improved immune response in previous studies. RANTES and CD40L play a pivotal role in host defense, and individuals lacking adequate expression are prone to virus and opportunistic infections. A total of 98 participants were enrolled in this study. The probands were asked to perform moderate physical activity, and bicycle stress tests were performed at the baseline and after 8 months of training to evaluate individual performance. RANTES and CD40L were found to be increased by long-term physical exercise. In particular, probands with a performance gain of ≥3% displayed a pronounced elevation of both markers, paired with a decrease in circulating IL6 levels and an improved lipid profile. In summary, we were able to highlight rising levels of serum RANTES and CD40L under the conditions of physical exercise. Taking their role in host defense into account, a conjunction of physical activity and the adaptive immune system could therefore be assumed. Furthermore, low inflammatory profiles in probands with a significant performance gain suggest a modulation through exercise rather than a generalized pro-inflammatory status.

Natural history of very severe aortic stenosis.

BACKGROUND: We sought to assess the outcome of asymptomatic patients with very severe aortic stenosis. METHODS AND RESULTS: We prospectively followed 116 consecutive asymptomatic patients (57 women; age, 67 + or - 16 years) with very severe isolated aortic stenosis defined by a peak aortic jet velocity (AV-Vel) > or = 5.0 m/s (average AV-Vel, 5.37 + or - 0.35 m/s; valve area, 0.63 + or - 0.12 cm(2)). During a median follow-up of 41 months (interquartile range, 26 to 63 months), 96 events occurred (indication for aortic valve replacement, 90; cardiac deaths, 6). Event-free survival was 64%, 36%, 25%, 12%, and 3% at 1, 2, 3, 4, and 6 years, respectively. AV-Vel but not aortic valve area was shown to independently affect event-free survival. Patients with an AV-Vel > or = 5.5 m/s had an event-free survival of 44%, 25%, 11%, and 4% at 1, 2, 3, and 4 years, respectively, compared with 76%, 43%, 33%, and 17% for patients with an AV-Vel between 5.0 and 5.5 m/s (P<0.0001). Six cardiac deaths occurred in previously asymptomatic patients (sudden death, 1; congestive heart failure, 4; myocardial infarction, 1). Patients with an initial AV-Vel > or = 5.5 m/s had a higher likelihood (52%) of severe symptom onset (New York Heart Association or Canadian Cardiovascular Society class >II) than those with an AV-Vel between 5.0 and 5.5 m/s (27%; P=0.03). CONCLUSIONS: Despite being asymptomatic, patients with very severe aortic stenosis have a poor prognosis with a high event rate and a risk of rapid functional deterioration. Early elective valve replacement surgery should therefore be considered in these patients.

The endocardial binary appearance ('binary sign') is an unreliable marker for echocardiographic detection of Fabry disease in patients with left ventricular hypertrophy.

AIMS: The binary sign, a binary appearance of the left ventricular endocardial border, was suggested to be an echocardiographic hallmark in diagnosing Fabry disease, a hereditary, lysosomal storage disorder. The aim of the present study was to examine the reliability of the binary sign as a screening tool to identify patients with Fabry disease. METHODS AND RESULTS: In total 309 subjects with an interventricular septum (IVS) thickness of ≥12 mm were investigated, of which 14 had a confirmed diagnosis of Fabry disease. Urinary globotriaosylceramide testing was used to rule out Fabry disease in the control group. From all patients echocardiographic images of the apical four-chamber view were analysed offline by a blinded observer. A binary sign was seen in 63 patients (20%), 4 had Fabry disease and 59 belonged to the control group. Although the proportion of binary signs in patients with Fabry disease was higher (29%) compared with the control group (20%) this difference was not statistically significant. The sensitivity and specificity were 28% (95% confidence interval (CI): 12-65%) and 80% (95% CI: 76-85%), respectively. In a logistic regression model adjusted for age, sex and presence of Fabry disease, the occurrence of a binary sign was highly dependent on the IVS thickness (odds ratio: 1.21; 95% CI: 1.1-1.35; P<0.001). CONCLUSION: The endocardial binary appearance is associated with the degree of septal hypertrophy but cannot adequately distinguish between patients with Fabry disease and patients with other causes of left ventricular hypertrophy.

Speckle Tracking-Derived Longitudinal Strain: Validation and Influence of Scanner Settings.

Speckle tracking-based strain analysis is an evolving technique for the assessment of left ventricular function. We evaluated the influence of machine settings on global longitudinal peak systolic strain (GLPSS) values in an everyday patient population (n = 35). In each patient, the four-chamber view was recorded multiple times with different machine parameters. Ejection fraction ranged between 10% and 76% and correlated well with GLPSS (r = -0.778). GLPSS was not altered systematically by modifications of gain and frame rate. Conversely, higher transducer frequencies (mean effect: 1.102%/MHz, p < 0.001, and 0.662%/MHz, p = 0.033, for harmonic and fundamental imaging frequencies, respectively) and lower sector depth (mean effect: -0.156%/cm, p < 0.001) were associated with a slight-but statistically significant-reduction in absolute GLPSS values. Intra- and inter-observer variability exhibited satisfactory repeatability. GLPSS analysis proved to be reproducible and robust in our patient cohort if common settings for adult echocardiography were applied.

MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease.

BACKGROUND: Fabry disease is a hereditary genetic defect resulting in reduced activity of the enzyme α-galactosidase-A and the accumulation of globotriaosylceramide (Gb3) in body fluids and cells. Gb3 accumulation was especially reported for the vascular endothelium in several organs. METHODS: Three Fabry disease patients were screened using a micro-RNA screen. An in vitro approach in human endothelial cells was used to determine miRNA regulation by Gb3. RESULTS: In a micro-RNA screen of three Fabry patients undergoing enzyme replacement therapy, we found that miRNAs let-7a and let-7d were significantly increased after therapy. We demonstrate in vitro in endothelial cells that Gb3 induced activation of NF-κB and activated downstream targets. In addition, NF-κB activity directly reduced let-7a and let-7d miRNA expression as inhibiting NF-kB nuclear entry abolished the Gb3 effects. CONCLUSION: We suggest that let-7a and let-7d are potential markers for enzyme activity and inflammation in Fabry disease patients.

Electrical optimization of cardiac resynchronization in chronic heart failure is associated with improved clinical long-term outcome.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment option for symptomatic chronic heart failure (CHF) patients with pharmacological baseline therapy, but not all patients benefit from device therapy. One reason for this may be inadequate device settings. In real-world practice, echocardiographic evaluation of atrioventricular (AV) delay is not performed in a high proportion of patients, as the effect of electrical optimization of CRT is an issue open for investigation. MATERIALS AND METHODS: We performed a retrospective observational study analysing the effect of AV-interval evaluation with echocardiography on long-term [32 (23?43) months] clinical outcome in 205 CHF patients. A stepwise Cox regression model including a co-morbidity score, failed AV-interval evaluation, satisfactory device function after the first implantation attempt, failure to reach 100% of the recommended renin-angiotensin system inhibitor and beta-blocker dose at follow-up and CRT device implantation compared with CRT in combination with an implanted cardioverter defibrillator (ICD) was applied. RESULTS: In the total study cohort, 124 (60.5%) patients had reached the primary combined endpoint death or cardiac hospitalization and 59 (28.8%) had died. Cox regression analysis revealed that failed AV-interval evaluation [HR = 1.72 (1.19-2.49), P = 0.004] non-optimized CHF pharmacotherapy dosages [HR = 2.12 (1.32-3.42), P = 0.002], the presence of a CRT/ICD combination device [HR = 1.87 (1.28-2.71), P = 0.001] and satisfactory device function after the first implantation attempt [HR = 0.44 (0.25-0.77), P = 0.004] were associated with the primary endpoint. CONCLUSION: Echocardiographic evaluation of the AV-interval in patients with CRT was independently associated with improved clinical outcome, impacting on daily clinical practice of HF patient care.

Assessment of left ventricular volume and ejection fraction: comparison of QGS and MBGS analyses of ECG-gated myocardial perfusion SPECT imaging.

OBJECTIVES: The purpose of this study was to compare quantitative ECG-gated single-photon emission computed tomography (SPECT) (QGS) and model-based ECG-gated single-photon emission computed tomography (MBGS) for determination of end-diastolic cardiac volume (EDV), end-systolic cardiac volume (ESV), and left ventricular ejection fraction (LVEF). The accuracy of both methods was evaluated by measurements obtained from contrast left ventriculography (LVG). METHODS: Forty-five patients (40 male, age: 55+/-11 years) with coronary artery disease were studied by angiography and ECG-gated SPECT using technetium-99m-sestamibi for the evaluation of myocardial perfusion and LVEF. Short axis SPECT images were analyzed by QGS and MBGS to estimate endocardial and epicardial surfaces and to derive EDV, ESV, and LVEF. RESULTS: EDV by gated SPECT (QGS: 187+/-71 ml; MBGS: 191+/-76 ml) were lower than corresponding values by LVG (203+/-59 ml), whereas ESV by gated SPECT (QGS: 121+/-62 ml; MBGS: 108+/-54 ml) were higher than by LVG (105+/-49 ml). Thus, LVEFs by gated SPECT (QGS: 39+/-12%; MBGS: 45+/-9%) were significantly lower than by LVG (50+/-15%). LVEF by MBGS was significantly higher than by QGS (P<0.05). A significant correlation was observed among QGS, MBGS, and LVG for the calculation of EDV, ESV, and LVEF. CONCLUSION: Measurements of LV volumes and LVEF by QGS and MBGS showed close agreement with each other and with results from LVG. However, both methods measure lower values for EDV and higher values for ESV and thus underestimate LVEF compared with LVG.

Role of adult bone marrow stem cells in the repair of ischemic myocardium: current state of the art.

OBJECTIVE: To review the milestones in stem cell therapy for ischemic heart disease from early basic science to large clinical studies and new therapeutic approaches. MATERIALS AND METHODS: Basic research and clinical trials (systematic review) were used. The heart has the ability to regenerate through activation of resident cardiac stem cells or through recruitment of a stem cell population from other tissues, such as bone marrow. Although the underlying mechanism is yet to be made clear, numerous studies in animals have documented that transplantation of bone marrow-derived stem cells or circulating progenitor cells following acute myocardial infarction and ischemic cardiomyopathy is associated with a reduction in infarct scar size and improvements in left ventricular function and myocardial perfusion. RESULTS: Cell-based cardiac therapy has expanded considerably in recent years and is on its way to becoming an established cardiovascular therapy for patients with ischemic heart disease. There have been recent insights into the understanding of mechanisms involved in the mobilization and homing of the imported cells, as well as into the paracrine effect, growth factors, and bioactive molecules. Additional information has been obtained regarding new stem cell sources, cell-based gene therapy, cell-enhancement strategies, and tissue engineering, all of which should enhance the efficacy of human cardiac stem cell therapy. CONCLUSIONS: The recently published trials using bone marrow-origin stem cells in cardiac repair reported a modest but significant benefit from this therapy. Further clinical research should aim to optimize the cell types utilized and their delivery mode, and pinpoint optimal time of cell transplantation.