Iron deficiency and all-cause mortality after myocardial infarction.

BACKGROUND: Data on the clinical significance of iron deficiency (ID) in patients with myocardial infarction (MI) are conflicting. This may be related to the use of various ID criteria. We aimed to compare the association of different ID criteria with all-cause mortality after MI. METHODS: Consecutive patients hospitalized for their first MI at a large tertiary heart center were included. We evaluated the association of different iron metabolism parameters measured on the first day after hospital admission with all-cause mortality. RESULTS: From the 1,156 patients included (aged 64±12 years, 25 % women), 194 (16.8 %) patients died during the median follow-up of 3.4 years. After multivariate adjustment, iron level ≤13 µmol/L (HR 1.67, 95 % CI 1.19-2.34) and the combination of iron level ≤12.8 µmol/L and soluble transferrin receptor (sTfR) ≥3 mg/L (HR 2.56, 95 % CI 1.64-3.99) termed as PragueID criteria were associated with increased mortality risk and had additional predictive value to the GRACE score. Compared to the model including iron level, the addition of sTfR improved risk stratification (net reclassification improvement 0.61, 95 % CI 0.52-0.69) by reclassifying patients into a higher-risk group. No association between ferritin level and mortality was found. 51 % of patients had low iron levels, and 58 % fulfilled the PragueID criteria. CONCLUSION: Iron deficiency is common among patients with the first MI. The PragueID criteria based on iron and soluble transferrin receptor levels provide the best prediction of mortality and should be evaluated in future interventional studies for the identification of patients potentially benefiting from intravenous iron therapy.

Development and validation of a prognostic score integrating remote heart failure symptoms and clinical variables in mortality risk prediction after myocardial infarction. The PragueMi score.

AIMS: While heart failure (HF) symptoms are associated with adverse prognosis after myocardial infarction (MI), they are not routinely used for patients' stratification. The primary objective of this study was to develop and validate a score to predict mortality risk after MI, combining remotely recorded HF symptoms and clinical risk factors, and to compare it against the guideline-recommended GRACE score. METHODS: A cohort study design using prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart centre between June 2017 and September 2022 was used. RESULTS: Data from 1,135 patients (aged 64±12 years, 26.7% women), were split into derivation (70%) and validation cohort (30%). Components of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) questionnaire and clinical variables were used as possible predictors. The best model included the following variables - age, heart failure history, admission creatinine and heart rate, ejection fraction at hospital discharge, and HF symptoms 1 month after discharge including walking impairment, leg swelling, and change in HF symptoms. Based on these variables, the PragueMi score was developed. In the validation cohort, the PragueMi score showed superior discrimination to the GRACE score for 6 months (AUC 90.1, 95% CI 81.8-98.4 vs. 77.4, 95% CI 62.2-92.5, p=0.04) and 1-year risk prediction (AUC 89.7, 95% CI 83.5-96.0 vs. 76.2, 95% CI 64.7-87.7, p=0.004). CONCLUSION: The PragueMi score combining heart failure symptoms and clinical variables performs better than the currently recommended GRACE score.

The prognosis of patients after myocardial infarction is heterogeneous. Thus, risk stratification is needed to identify and intervene patients at increased risk. While heart failure (HF) symptoms are associated with adverse prognosis, they are not used for patients' stratification. We have developed and internally validated the PragueMi score, which integrates clinical risk factors at the time of hospitalization and HF symptoms determined remotely by a questionnaire 1 month after hospital discharge. PragueMi score was able to better stratify patients' risk as compared to the currently recommended GRACE score.

Remote Heart Failure Symptoms Assessment After Myocardial Infarction Identifies Patients at Risk for Death.

BACKGROUND: Heart failure is a common complication after myocardial infarction (MI) and is associated with increased mortality. Whether remote heart failure symptoms assessment after MI can improve risk stratification is unknown. The authors evaluated the association of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) with all-cause mortality after MI. METHODS AND RESULTS: Prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart center between June 2017 and September 2022 were used. Patients remotely completed the KCCQ 1 month after discharge. A total of 1135 (aged 64±12 years, 26.7% women) of 1721 eligible patients completed the KCCQ. Ranges of KCCQ scores revealed that 30 (2.6%), 114 (10.0%), 274 (24.1%), and 717 (63.2%) had scores <25, 25 to 49, 50 to 74, and ≥75, respectively. During a mean follow-up of 46 months (interquartile range, 29-61), 146 (12.9%) died. In a fully adjusted analysis, KCCQ scores <50 were independently associated with mortality (hazard ratio [HR], 6.05 for KCCQ <25, HR, 2.66 for KCCQ 25-49 versus KCCQ ≥50; both P<0.001). Adding the 30-day KCCQ to clinical risk factors improved risk stratification: change in area under the curve of 2.6 (95% CI, 0.3-5.0), Brier score of -0.6 (95% CI, -1.0 to -0.2), and net reclassification improvement of 0.71 (95% CI, 0.45-1.04). KCCQ items most strongly associated with mortality were walking impairment, leg swelling, and change in symptoms. CONCLUSIONS: Remote evaluation of heart failure symptoms using the KCCQ among patients recently discharged for MI identifies patients at risk for mortality. Whether closer follow-up and targeted therapy can reduce mortality in high-risk patients warrants further study.

Cholesterol associated genetic risk score and acute coronary syndrome in Czech males.

BACKGROUND: Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. METHODS AND RESULTS: We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. CONCLUSIONS: We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.

From Cardiovascular Prevention and Differential Diagnosis to the Treatment of Myocardial Damage-Experimental and Human Perspectives.

Cardiovascular diseases are characterized by many clinical, morphological, functional, and biochemical markers, including age, sex, genetic factors, plasma lipids, glycemia, and many other laboratory parameters [...].

The way to data: opinions and recommendations for the provision of health data for secondary use.

Healthcare data held by state-run organisations is a valuable intangible asset for society. Its use should be a priority for its administrators and the state. A completely paternalistic approach by administrators and the state is undesirable, however much it aims to protect the privacy rights of persons registered in databases. In line with European policies and the global trend, these measures should not outweigh the social benefit that arises from the analysis of these data if the technical possibilities exist to sufficiently protect the privacy rights of individuals. Czech society is having an intense discussion on the topic, but according to the authors, it is insufficiently based on facts and lacks clearly articulated opinions of the expert public. The aim of this article is to fill these gaps. Data anonymization techniques provide a solution to protect individuals' privacy rights while preserving the scientific value of the data. The risk of identifying individuals in anonymised data sets is scalable and can be minimised depending on the type and content of the data and its use by the specific applicant. Finding the optimal form and scope of deidentified data requires competence and knowledge on the part of both the applicant and the administrator. It is in the interest of the applicant, the administrator, as well as the protected persons in the databases that both parties show willingness and have the ability and expertise to communicate during the application and its processing.

Attenuation of Hypocretin/Orexin Signaling Is Associated With Increased Mortality After Myocardial Infarction.

Background The hypocretin/orexin system has been shown to play a role in heart failure. Whether it also influences myocardial infarction (MI) outcomes is unknown. We evaluated the effect of the rs7767652 minor allele T associated with decreased transcription of the hypocretin/orexin receptor-2 and circulating orexin A concentrations on mortality risk after MI. Methods and Results Data from a single-center, prospectively designed registry of consecutive patients hospitalized for MI at a large tertiary cardiology center were analyzed. Patients without previous history of MI or heart failure were included. A random population sample was used to compare allele frequencies in the general population. Out of 1009 patients (aged 64±12 years, 74.6% men) after MI, 6.1% were homozygotes (TT) and 39.4% heterozygotes (CT) for minor allele. Allele frequencies in the MI group did not differ from 1953 subjects from general population (χ2 P=0.62). At index hospitalization, MI size was the same, but ventricular fibrillation and the need for cardiopulmonary resuscitation were more prevalent in the TT allele variant. Among patients with ejection fraction ≤40% at discharge, the TT variant was associated with a lower increase in left ventricular ejection fraction during follow-up (P=0.03). During the 27-month follow-up, there was a statistically significant association of the TT variant with increased mortality risk (hazard ratio [HR], 2.83; P=0.001). Higher circulating orexin A was associated with a lower mortality risk (HR, 0.41; P<0.05). Conclusions Attenuation of hypocretin/orexin signaling is associated with increased mortality risk after MI. This effect may be partially explained by the increased arrhythmic risk and the effect on the left ventricular systolic function recovery.

Heart failure-related quality-of-life impairment after myocardial infarction.

AIMS: Recent advances in therapy led to a significant decrease in mortality and morbidity after myocardial infarction (MI). However, little is known about quality of life (QoL) after MI. We examined heart failure (HF)-related quality-of-life (QoL) impairment, its trajectories, and determinants after MI. METHODS: Data from a single-center prospectively designed registry of consecutive patients hospitalized for MI at a large tertiary cardiology center were utilized. At 1 month and 1 year after hospital discharge, patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: In total, 850 patients (aged 65 ± 12 years, 27% female) hospitalized between June 2017 and October 2020 completed KCCQ at 1 month after discharge. Of these, 38.7% showed HF-related QoL impairment (KCCQ ≤ 75). In addition to characteristics of MI (MI size, diuretics need, heart rate), comorbidities as renal dysfunction and anemia were associated with QoL impairment. Of the 673 eligible, 500 patients (74.3%) completed KCCQ at 1 year after MI. On average, QoL improved by 5.9 ± 16.8 points during the first year after MI (p < 0.001); but, in 18% of patients QoL worsened. Diabetes control and hemoglobin level at the time of hospitalization were associated with QoL worsening. CONCLUSION: Two out of 5 patients after MI present with HF-related QoL impairment. In addition to guideline-directed MI management, careful attention to key non-cardiac comorbidities as chronic kidney disease, anemia and diabetes may lead to further augmentation of the benefit of modern therapies in terms of QoL.

Trajectories and determinants of left ventricular ejection fraction after the first myocardial infarction in the current era of primary coronary interventions.

Background: Left ventricular ejection fraction (EF) is an independent predictor of adverse outcomes after myocardial infarction (MI). However, current data on trajectories and determinants of EF are scarce. The present study aimed to describe the epidemiology of EF after MI. Methods: Data from a single-center prospectively-designed registry of consecutive patients hospitalized at a large tertiary cardiology center were utilized. Results: Out of 1,593 patients in the registry, 1,065 were hospitalized for MI type I (65.4% STEMI) and had no previous history of heart failure or MI. At discharge, EF < 40% was present in 238 (22.3%), EF 40-50% in 326 (30.6%) and EF > 50% in 501 (47.0%). Patients with EF < 40% were often those who suffered subacute and anterior STEMI, had higher heart rate at admission and higher maximal troponin level, and had more often HF signs requiring intravenous diuretics. Among subjects with EF < 40%, the follow-up EF was available in 166 (80% of eligible). Systolic function recovered to EF > 50% in 39 (23.1%), slightly improved to EF 40-50% in 44 (26.0%) and remained below 40% in 86 (50.9%). Systolic function improvement to EF > 40% was predicted by lower severity of coronary atherosclerosis, lower leukocyte count, and the absence of atrial fibrillation. Conclusions: Despite recent improvements in in-hospital MI care, one in five patients has systolic dysfunction at hospital discharge. Out of these, EF improves in 51%, and full recovery is observed in 23%. The severity of coronary atherosclerosis, inflammatory response to MI, and atrial fibrillation may affect EF recovery.

International Union of Angiology (IUA) consensus paper on imaging strategies in atherosclerotic carotid artery imaging: From basic strategies to advanced approaches.

Cardiovascular disease (CVD) is the leading cause of mortality and disability in developed countries. According to WHO, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to major adverse cardiac and cerebral events. Early detection and care for individuals at high risk could save lives, alleviate suffering, and diminish economic burden associated with these diseases. Carotid artery disease is not only a well-established risk factor for ischemic stroke, contributing to 10%-20% of strokes or transient ischemic attacks (TIAs), but it is also a surrogate marker of generalized atherosclerosis and a predictor of cardiovascular events. In addition to diligent history, physical examination, and laboratory detection of metabolic abnormalities leading to vascular changes, imaging of carotid arteries adds very important information in assessing stroke and overall cardiovascular risk. Spanning from carotid intima-media thickness (IMT) measurements in arteriopathy to plaque burden, morphology and biology in more advanced disease, imaging of carotid arteries could help not only in stroke prevention but also in ameliorating cardiovascular events in other territories (e.g. in the coronary arteries). While ultrasound is the most widely available and affordable imaging methods, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), their combination and other more sophisticated methods have introduced novel concepts in detection of carotid plaque characteristics and risk assessment of stroke and other cardiovascular events. However, in addition to robust progress in usage of these methods, all of them have limitations which should be taken into account. The main purpose of this consensus document is to discuss pros but also cons in clinical, epidemiological and research use of all these techniques.

Cardiovascular, Metabolic and Inflammatory Changes after Ovariectomy and Estradiol Substitution in Hereditary Hypertriglyceridemic Rats.

BACKGROUND: If menopause is really independent risk factor for cardiovascular disease is still under debate. We studied if ovariectomy in the model of insulin resistance causes cardiovascular changes, to what extent are these changes reversible by estradiol substitution and if they are accompanied by changes in other organs and tissues. METHODS: Hereditary hypertriglyceridemic female rats were divided into three groups: ovariectomized at 8th week (n = 6), ovariectomized with 17-ß estradiol substitution (n = 6), and the sham group (n = 5). The strain of abdominal aorta measured by ultrasound, expression of vascular genes, weight and content of myocardium and also non-cardiac parameters were analyzed. RESULTS: After ovariectomy, the strain of abdominal aorta, expression of nitric oxide synthase in abdominal aorta, relative weight of myocardium and of the left ventricle and circulating interleukin-6 decreased; these changes were reversed by estradiol substitution. Interestingly, the content of triglycerides in myocardium did not change after ovariectomy, but significantly increased after estradiol substitution while adiposity index did not change after ovariectomy, but significantly decreased after estradiol substitution. CONCLUSION: Vascular and cardiac parameters under study differed in their response to ovariectomy and estradiol substitution. This indicates different effects of ovariectomy and estradiol on different cardiovascular but also extracardiac structures.

Omega-3 Polyunsaturated Fatty Acids-Vascular and Cardiac Effects on the Cellular and Molecular Level (Narrative Review).

In the prevention and treatment of cardiovascular disease, in addition to the already proven effective treatment of dyslipidemia, hypertension and diabetes mellitus, omega-3 polyunsaturated fatty acids (n-3 PUFAs) are considered as substances with additive effects on cardiovascular health. N-3 PUFAs combine their indirect effects on metabolic, inflammatory and thrombogenic parameters with direct effects on the cellular level. Eicosapentaenoic acid (EPA) seems to be more efficient than docosahexaenoic acid (DHA) in the favorable mitigation of atherothrombosis due to its specific molecular properties. The inferred mechanism is a more favorable effect on the cell membrane. In addition, the anti-fibrotic effects of n-3 PUFA were described, with potential impacts on heart failure with a preserved ejection fraction. Furthermore, n-3 PUFA can modify ion channels, with a favorable impact on arrhythmias. However, despite recent evidence in the prevention of cardiovascular disease by a relatively high dose of icosapent ethyl (EPA derivative), there is still a paucity of data describing the exact mechanisms of n-3 PUFAs, including the role of their particular metabolites. The purpose of this review is to discuss the effects of n-3 PUFAs at several levels of the cardiovascular system, including controversies.

Increased pulsatility index is associated with adverse outcomes in left ventricular assist device recipients.

AIMS: Recipients of left ventricular assist devices (LVAD) are exposed to increased risk of adverse clinical events. One of the potential contributing factors is non-pulsatile flow generated by LVAD. We evaluated the association of flow patterns in carotid arteries and of increased arterial stiffness with death and cerebrovascular events in LVAD recipients. METHODS AND RESULTS: We analysed data from 83 patients [mean age 54 ± 15 years; 12 women; HeartMate II (HMII), n = 34; HeartMate 3 (HM3), n = 49]. Pulsatile and resistive indexes, atherosclerotic changes in carotid arteries (measured by duplex ultrasound), and arterial stiffness [measured by Endo-PAT 2000 as the augmentation index standardized for heart rate (AI@75)] were evaluated 3 and 6 months after LVAD implantation. Sixteen patients died during follow-up (27.3 months; interquartile range 15.7-44.3). After adjusting for the main variables examined, the pulsatility index measured at 3 months was positively associated with increased hazard ratios (HR) for death and cerebrovascular events [HR 9.8, 95% confidence interval (CI) 1.62-59.42], with HR increasing after adding AI@75 to the model (HR 18.8, 95% CI 2.44-145.50). In HM3 recipients, HR was significantly lower than in HMII recipients (HR 0.31, 95% CI 0.11-0.91), but the significance disappeared after adding AI@75 to the model (HR 0.33, 95% CI 0.09-1.18). CONCLUSIONS: The risk of death and cerebrovascular events in LVAD recipients is associated with increased pulsatility index in carotid arteries and potentiated by increased arterial stiffness. The same risk is attenuated by HM3 LVAD implantation, but this effect is weakened by increased arterial stiffness.

The effect of long-term left ventricular assist device support on flow-sensitive plasma microRNA levels.

BACKGROUND: Implantation of current generation left ventricular assist devices (LVADs) in the treatment of end-stage heart failure (HF), not only improves HF symptoms and end-organ perfusion, but also leads to cellular and molecular responses, presumably in response to the continuous flow generated by these devices. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in multiple biological processes, including the pathogenesis of HF. In our study, we examined the influence of long-term LVAD support on changes in flow-sensitive miRNAs in plasma. MATERIALS AND METHODS: Blood samples from patients with end-stage heart failure (N = 33; age = 55.7 ± 11.6 years) were collected before LVAD implantation and 3, 6, 9, and 12 months after implantation. Plasma levels of the flow-sensitive miRNAs; miR-10a, miR-10b, miR-146a, miR-146b, miR-663a, miR-663b, miR-21, miR-155, and miR-126 were measured using quantitative PCR. RESULTS: Increasing quantities of miR-126 (P < 0.03) and miR-146a (P < 0.02) was observed at each follow-up visit after LVAD implantation. A positive association between miR-155 and Belcaro score (P < 0.04) and an inverse correlation between miR-126 and endothelial function, measured as the reactive hyperemia index (P < 0.05), was observed. CONCLUSIONS: Our observations suggest that after LVAD implantation, low pulsatile flow up-regulates plasma levels of circulating flow-sensitive miRNAs, contributing to endothelial dysfunction and vascular remodeling.

The Effect of Artificial Pulsatility on the Peripheral Vasculature in Patients With Continuous-Flow Ventricular Assist Devices.

BACKGROUND: Implantation of left-ventricular assist systems (LVASs) has become the standard of care for advanced heart failure (HF). The absence of pulsatility in previous devices contributes to vascular and endothelial dysfunction related to atherosclerotic or vascular complications. We hypothesized that the artificial pulsatility provided by the HeartMate 3 (HM3) (Abbott, Chicago, IL) LVAS would exert a favourable effect on the vasculature. METHODS: In 32 patients implanted with HM3 (5 female patients, mean age 55 ± 13.6 years), the reactive hyperemia index (RHI) and peripheral augmentation index (AI), markers of endothelial function and arterial stiffness, were measured with an EndoPAT2000 before and in the third and sixth month after implantation. RHI and AI data from 30 HeartMate II (HM II) (Abbott) recipients in the third and sixth month after implantation, from 15 patients with advanced HF without LVASs and from 13 healthy volunteers were also analyzed. RESULTS: In HM3 recipients, the mean RHI significantly decreased at 3 and 6 months after implantation. The RHI was substantially lower at baseline than that of healthy or the HF reference group. Increasing AI values, indicating worsening arterial stiffness, were also observed. Similar trends were observed in HM II recipients between the third and sixth months but with higher absolute values of RHI and AI. CONCLUSIONS: We detected impaired vascular function in HM3 patients and provided additional evidence on the negative effect of low pulsatility on vascular function after LVAS implantation. The results suggest that the artificial pulsatility of the HM3 does not avert the progression of endothelial dysfunction.

Very low lipoprotein(a) and increased mortality risk after myocardial infarction.

BACKGROUND: Inconclusive data exist on risk associated with Lp(a) in patients after myocardial infarction (MI). Aims of the present study were to evaluate the association of Lp(a) level with total mortality and recurrent cardiovascular events. DESIGN AND METHODS: Single center prospective registry of consecutive patients hospitalized for acute myocardial infarction between June 2017 and June 2020 at a large tertiary cardiac center with available blood samples drawn <24h of admission. RESULTS: Data from 851 consecutive patients hospitalized for MI were evaluated. During the median follow-up of 19 months (interquartile range 10-27), 58 (6.8%) patients died. Nonlinear modelling revealed a U-shaped association between Lp(a) and total mortality risk. Compared to patients with Lp(a) ranging between 10-30 nmol/L and after multivariate adjustment, total mortality risk was increased both in patients with Lp(a)<7 nmol/L (hazard ratio (HR) 4.08, 95% confidence interval (CI) 1.72-9.68) and Lp(a) ≥125 nmol/L (HR 2.92, 95% CI 1.16-7.37), respectively. Similarly, the risk of combined endpoint of acute coronary syndrome recurrence or cardiovascular mortality was increased both in patients with low (sub-HR 2.60, 95% CI 1.33-5.08) and high (sub-HR 2.10, 95% CI 1.00-4.39) Lp(a). Adjustment for heart failure signs at the time of hospitalization weakened the association with total mortality and recurrent cardiovascular events. CONCLUSIONS: In the present analysis, both high and low concentrations of Lp(a) were associated with an increased risk of total mortality and recurrent cardiovascular events after MI. The excess of mortality associated with Lp(a) was partially attributable to more prevalent heart failure.

The Truth About Fish (Oil) in the Treatment of Dyslipidemia.

PURPOSE OF REVIEW: To discuss the effect of fish oils on dyslipidemias and associated disorders. RECENT FINDINGS: The most important lipid effect of fish oils is reducing plasma triglycerides and the main potential protection against cardiovascular events is very probably mediated also through other mechanisms including anti-inflammatory ones. The best results are available for omega-3 fatty acids, namely, eicosapentaenoic acid. Less evidence is available for the impact of ω-3 fatty acids on liver steatosis/steatohepatitis and acute pancreatitis. In addition, particular fish oils have variable content of saturated and unsaturated fatty acids with different anti- or pro-oxidative potential, and the suboptimal ratio of these compounds could attenuate or abolish their beneficial properties. Fish products with optimal proportion of fatty acids, particularly high content of eicosapentaenoic acid, could be recommended to patients with dyslipidemias, especially to those at high risk for cardiovascular disease; less evidence is available for liver disease and acute pancreatitis.

Deleterious Effects of Hyperactivity of the Renin-Angiotensin System and Hypertension on the Course of Chemotherapy-Induced Heart Failure after Doxorubicin Administration: A Study in Ren-2 Transgenic Rat.

Doxorubicin's (DOX) cardiotoxicity contributes to the development of chemotherapy-induced heart failure (HF) and new treatment strategies are in high demand. The aim of the present study was to characterize a DOX-induced model of HF in Ren-2 transgenic rats (TGR), those characterized by hypertension and hyperactivity of the renin-angiotensin-aldosterone system, and to compare the results with normotensive transgene-negative, Hannover Sprague-Dawley (HanSD) rats. DOX was administered for two weeks in a cumulative dose of 15 mg/kg. In HanSD rats DOX administration resulted in the development of an early phase of HF with the dominant symptom of bilateral cardiac atrophy demonstrable two weeks after the last DOX injection. In TGR, DOX caused substantial impairment of systolic function already at the end of the treatment, with further progression observed throughout the experiment. Additionally, two weeks after the termination of DOX treatment, TGR exhibited signs of HF characteristic for the transition stage between the compensated and decompensated phases of HF. In conclusion, we suggest that DOX-induced HF in TGR is a suitable model to study the pathophysiological aspects of chemotherapy-induced HF and to evaluate novel therapeutic strategies to combat this form of HF, which are urgently needed.

Changes in circulating stem cells and endothelial progenitor cells over a 12-month period after implantation of a continuous-flow left ventricular assist device.

INTRODUCTION: Changes in circulating CD34+CD45low stem cells (SC) and CD34+CD45low+KDR+ endothelial progenitor cells (EPC) may reflect pathological endothelial activation. Non-pulsatile/continuous-flow left ventricular assist devices (CF-LVAD) can enhance this process. The aim of this study was to analyse the impact of 12-month CF-LVAD treatment on SC and EPC. METHODS: We analysed changes in SC and EPC from the pre-implantation period up until 12 months after implantation over 3-month intervals in 14 patients. Data from 12 patients with heart failure (HF) and from 13 healthy volunteers were used as controls. RESULTS: Baseline EPC were significantly higher in CF-LVAD and HF patients than in healthy controls, substantially decreasing 3 months after CF-LVAD implantation and then returning to high baseline values at 12 months. CONCLUSIONS: Changes in circulating SC and EPC may reflect pathological endothelial activation after CF-LVAD implantation.