Left Ventricular Systolic Heart Failure Research Articles

Transcatheter transfemoral aortic valve replacement in a patient with acromegaly and severe left ventricular myocardial hypertrophy. Case report

Main causes of secondary hypertrophic cardiomyopathy include acromegalic cardiomyopathy. Heart damage in patients with the acromegaly is mediated both by the direct action of growth hormone and insulin-like growth factor-1, and increased deposition of collagen and lymphomononuclear cells in the myocardium, which leads to architectural changes, disturbances in fluid and electrolyte balance, severe left ventricular myocardial hypertrophy, diastolic and systolic left ventricular dysfunction and chronic heart failure. This article presents the world's first described observation demonstrating the possibility of successful transfemoral aortic valve repair to a comorbid patient with severe aortic stenosis according to the potential risks caused by the active form of the acromegaly.

Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study.

A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot. Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation. A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%-44%] at baseline to 42% [32%-50%] at early follow-up (P<0.001) and remained improved from baseline thereafter (P≤0.002). The QRS duration decreased from 180 [160-205] ms at baseline to 152 [133-182] ms at early follow-up (P<0.001) and remained decreased at intermediate and late follow-up (P≤0.001). Patients with upgraded CRT had consistent improvement in left ventricular ejection fraction and QRS duration at each time point (P≤0.004). Patients had a significantly improved New York Heart Association functional class after CRT implantation at each time point compared with baseline (P≤0.002). The transplant-free survival rates at 3, 5, and 8 years after CRT implantation were 85%, 79%, and 73%. In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population.

The let-7b-5p, miR-326, and miR-125a-3p are associated with left ventricular systolic dysfunction in post-myocardial infarction.

Acute ST-elevation myocardial infarction (STEMI) can lead to adverse cardiac remodeling, resulting in left ventricular systolic dysfunction (LVSd) and heart failure. Epigenetic regulators, such as microRNAs, may be involved in the physiopathology of LVSd. This study explored microRNAs in peripheral blood mononuclear cells (PBMC) of post-myocardial infarction patients with LVSd. Post-STEMI patients were grouped as having (LVSd, n = 9) or not LVSd (non-LVSd, n = 16). The expression of 61 microRNAs was analyzed in PBMC by RT-qPCR and the differentially expressed microRNAs were identified. Principal Component Analysis stratified the microRNAs based on the development of dysfunction. Predictive variables of LVSd were investigated through logistic regression analysis. A system biology approach was used to explore the regulatory molecular network of the disease and an enrichment analysis was performed. The let-7b-5p (AUC: 0.807; 95% CI: 0.63-0.98; p = 0.013), miR-125a-3p (AUC: 0.800; 95% CI: 0.61-0.99; p = 0.036) and miR-326 (AUC: 0.783; 95% CI: 0.54-1.00; p = 0.028) were upregulated in LVSd (p < 0.05) and discriminated LVSd from non-LVSd. Multivariate logistic regression analysis showed let-7b-5p (OR: 16.00; 95% CI: 1.54-166.05; p = 0.020) and miR-326 (OR: 28.00; 95% CI: 2.42-323.70; p = 0.008) as predictors of LVSd. The enrichment analysis revealed association of the targets of these three microRNAs with immunological response, cell-cell adhesion, and cardiac changes. LVSd alters the expression of let-7b-5p, miR-326, and miR-125a-3p in PBMC from post-STEMI, indicating their potential involvement in the cardiac dysfunction physiopathology and highlighting these miRNAs as possible LVSd biomarkers.

PO-01-208 A COMPUTATIONAL MODEL TO TRACK CHANGES IN LEFT VENTRICULAR END-DIASTOLIC PRESSURE DURING ATRIAL FIBRILLATION

Heart failure and Atrial Fibrillation (AF) commonly occur concomitantly, resulting in significant morbidity and mortality. Thus, monitoring of heart failure status is essential in directing medical therapy in these patients. Left ventricular (LV) filling pressures are one of the most important parameters in assessing worsened or acutely decompensated left heart failure, however current LV pressure monitoring strategies include invasive devices and catheterization. Our study aims to develop a computational model of heart failure in AF and demonstrate that beat-to-beat variations in RR intervals during AF can be exploited to predict changes in LV filling pressure. We used a modified Research CardioVascular SIMulator (RCVSIM) human cardiovascular model to simulate an intact circulatory system in patients with AF over 300 seconds. To simulate beat-by-beat variation of rhythm in AF, the length of each RR-interval was drawn randomly from a Mixed Gaussian Distribution. We modelled worsening HF by changing LV end-systolic compliance in the simulator, using compliances ranging from 1 to 3.5 mL/mmHg, with interval increases in compliance of 0.1 mL/mmHg. Stroke volumes, RR-intervals, and LV end-diastolic pressures are recorded for each simulation. This was repeated for mean heart rates from 60 to 110 beats per minute. Stroke volumes were found to have a strong linear correlation with the previous beat’s RR-interval for all mean heart rates tested (Spearman rho = 0.9-0.97). In Figure 1 below, we show the slope of the RR-interval versus stroke volume (SV/RR-interval) plotted against average LV end-diastolic pressure for all LV systolic compliances noted above and a mean heart rate of 84 beats per minute. A cubic function fit to this plot shows excellent goodness-of-fit with the simulated data with a coefficient of determination (R2) of 0.99. This relationship remained consistent for all mean heart rates tested, and all cubic fits had R2 greater than 0.98. Our study provides a highly accurate model for estimating LV end-diastolic pressures over a broad range of LV systolic heart failure in simulated AF patients using only stroke volume and RR-intervals. Further work using photoplethysmography or continuous non-invasive arterial pressure (CNAP) monitoring could potentially be used to obtain these measures non-invasively, thus leading to a non-invasive method for tracking heart failure in patients with AF.

Effect of low-level laser physiotherapy on left ventricular function among patients with chronic systolic heart failure

BackgroundLow-level laser therapy (LLLT) is a promising noninvasive physiotherapeutic approach that has been demonstrated to improve cardiac performance. This study aimed to assess the impact of low-level laser therapy on cardiac functions and clinical status in patients with chronic left ventricular systolic heart failure who were not candidates for cardiac revascularization or resynchronization. A case series of 27 patients received a course of low-level laser physiotherapy, the clinical outcomes, echocardiographic parameters, and serum nitric oxide levels were evaluated before and after LLLT.ResultsOf the total patients enrolled in the study, 21 (or 77.8%) were male, with a mean age of 57.7 ± 6.89 years. NYHA classification significantly improved after low-level laser therapy, 15 patients were in class III,12 were in class IV, and no one was in class II before laser therapy while after laser therapy; 25 patients shifted to class II, two patients were in class III with P < 0.001, Six-minute walk distance test was performed, and the results showed that the mean of 6MWT was less than 200 m (148.556 ± 39.092) before the study but increased to more than 300 after laser therapy (385.074 ± 61.740), left ventricular ejection fraction before laser therapy was 26 ± 7.5 while after laser therapy it became 30 ± 8.6 but diastolic function did not change after low-level laser therapy, the mean peak TR pressure was 40.0 ± 9.0 mmHg and 33.0 ± 7.0 before and after laser therapy respectively P < 0.001. A significant change was observed in NO level from 4.1 ± 1.4 IU/ml before laser therapy to 5.2 ± 1.7 IU/ml after laser therapy P < 0.001.ConclusionsLow-level laser therapy may add benefits to improve symptoms, clinical condition, and quality of life in patients with left ventricular systolic dysfunction, further studies are necessary to evaluate the changes in cardiac functions at a longer follow-up duration.

Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients: A Five-Year Retrospective Study in 10 Centers.

Cardiotoxicity as a result of anthracycline chemotherapy has been linked to increased morbidity and mortality in breast cancer patients. There is a need for early detection through risk factor identification. To date, no large multicenter study has been conducted to describe the incidence, risk factors and clinical and demographic profiles of breast cancer patients with anthracycline-induced cardiotoxicity (AIC) in the Philippines. This was a nationwide multicenter retrospective cohort study among adult breast cancer patients who underwent anthracycline chemotherapy from 2015 to 2020 in 10 sites in the Philippines. Baseline characteristics and possible risk factors for AIC were retrieved from medical records and cancer registries. AIC was defined as a reduction of left ventricular ejection fraction (LVEF) by > 10% from baseline to a value of < 53% or the development of overt left ventricular systolic dysfunction or heart failure (HF). Odds ratios from logistic regression were computed to determine risk factors associated with AIC using STATA-15.0 software. Out of 341 patients included, 33 had AIC, accounting for an incidence of 9.68%. Nine patients (2.6%) had clinical HF. AIC patients had a mean age of 53.91 ± 10.84 years. Breast cancer AIC patients were significantly older and had lower body mass index (BMI) than those without AIC. AIC patients had significantly more comorbidities, especially hypertension and atrial fibrillation. Multivariate analysis showed that patients with any preexisting comorbidity are approximately 12.37 times as likely to have AIC, while those with concurrent chemotherapy are 0.07 times or 93% less likely to have AIC. Among adult breast cancer patients undergoing anthracycline chemotherapy, we determined a high incidence of cardiotoxicity at 9.68%. Having preexisting comorbidities gave patients 12 times increased odds of developing anthracycline cardiotoxicity. The presence of concurrent non-anthracycline chemotherapy showed an inverse association with the development of AIC which we attribute largely to patient selection in a retrospective study. The significantly higher propensity for AIC development in patients with preexisting comorbidities may warrant closer monitoring and control of patient comorbidities such as hypertension among patients undergoing anthracycline chemotherapy.

The new 2022 ESC Guidelines on Cardio-oncology and their impact on the Acute Cardiovascular Care Society.

In this perspective piece on the recently published ESC Guidelines on Cardio-oncology and the Consensus Statements from the Acute Cardiovascular Care Association, we summarize key learning points regarding the management of acute cardiovascular disease in patients with cancer. This document outlines where other pre-existing ESC Guidelines can be applied to the management of acute cardiovascular disease in patients with cancer while simultaneously highlighting important gaps in knowledge that require further research. Cancer and cardiovascular disease share common risk factors and often co-exist, especially in older patients. In addition, patients with cancer undergoing active treatment are exposed to multiple, potentially cardiotoxic drugs, which may manifest as a variety of cardiovascular events, including left-ventricular systolic dysfunction and heart failure, arrhythmias, hypertension, or acute venous and arterial vascular events. Knowledge about potential causative cancer therapeutics is necessary for rapid recognition and management to improve cardiovascular outcomes and guide ongoing cancer treatment. Specifically, the importance of rapidly interrupting culprit cancer drugs is highlighted, as well as instituting standard guideline-based therapies for conditions such as acute heart failure and acute coronary syndromes [ST-elevation myocardial infarction and high-risk non-ST-elevation acute coronary syndrome (ACS)]. Given the high prevalence of thrombocytopenia and increased bleeding risk in patients with cancer, we are provided with platelet cut-offs for the use of different antiplatelet agents and anticoagulants for patients with ACS and atrial arrhythmias. In contrast, given the hypercoagulable milieu of cancer, we are provided information regarding types of anticoagulants, drug-drug interactions, and duration of anticoagulation in patients with acute venous thromboembolism, as well as for atrial fibrillation. They also discuss the diagnostic and treatment strategies for the unique cardiotoxicities seen with novel cancer therapeutics such as immune checkpoint inhibitors and chimeric receptor antigen T-cell therapy. Last, but not least, the authors emphasize that the care of these patients requires close collaboration between cardiology and oncology to maximize both cardiovascular and cancer outcomes.

Peripartum Cardiomyopathy: Case Reports

Peripartum cardiomyopathy (PPCM) is a potentially fatal peripartum condition marked by left ventricular systolic dysfunction and heart failure in the absence of any established cardiac illness. Though its prevalence is increasing, there is still ambiguity about its prevalence, pathophysiology, and best management strategy. Our case study is about a patient who was hospitalized for shortness of breath that quickly worsened into asthma cardiale shortly after spontaneous birth. Because the origin of the symptoms was determined to be heart failure caused by peripartum cardiomyopathy, diuretics, inotropes, beta-blockers, and ACEIs were used to treat the symptoms. Mechanical cardiac assistance was unnecessary. Within three weeks, the symptoms of heart failure eased, and the left ventricular ejection fraction returned to its original level.

Cardiac resynchronization considerations in left bundle branch block.

Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP) is an established treatment for patients with left ventricular systolic heart failure and intraventricular conduction delay resulting in wide QRS. Seminal trials demonstrating mortality benefit from CRT were conducted in patients with wide left bundle branch block (LBBB) pattern on electrocardiogram (ECG) and evidence of clinical heart failure. The presence of conduction block was assumed to correlate with commonly applied criteria for LBBB. More recent data has challenged this assertion, revealing that LBBB pattern may include distinct underlying pathophysiology, including patients with complete conduction block, either at the left-sided His fibers or the proximal left bundle, intact Purkinje activation with wide LBBB-like QRS, and patients demonstrating both proximal block and distal delay. Currently, BiVP-CRT is indicated for all QRS duration ≥150 ms and may be considered for BBB patterns from 130 to 149 ms with robust clinical data to support its use. Despite this, however, there remains a significant number of non-responders to BVP. Conduction system pacing (CSP) has emerged as an alternative approach to deliver CRT and correct QRS in patients with conduction block. Newer hybrid approaches which combine CSP and traditional BiVP-CRT and may hold promise for patients with IP or mixed-level block. As various approaches to CRT continue to be studied, physiologic phenotyping of the LBBB pattern remains an important consideration.

Management and treatment of cardiotoxicity due to anticancer drugs: 10 questions and answers.

Since the introduction of anthracyclines into clinical practice in the 1960s, chemotherapy has always been associated with cardiotoxicity. Patients on cardiotoxic drugs can develop a wide range of cardiovascular diseases, including left ventricular (LV) systolic dysfunction and heart failure (HF), arrhythmias, hypertension, and coronary artery disease (CAD). The rising number of cancer patients, population ageing, and the frequent overlap of cardiovascular and oncological diseases have highlighted the importance of close collaboration between cardiologists and oncologists. As a result, in 1995, cardiologists at the IEO (European Institute of Oncology) coined the term cardioncology, a new discipline focused on the dynamics of cardiovascular disease in cancer patients. Given the complex scenario characterized by a constant dialogue between the oncological condition and cardiovascular comorbidity, it is essential for the clinician to get the knowledge to properly fulfill the needs of the oncological patient under cardiotoxic treatment. Through the answer to 10 questions, we aim to describe the complex issue of cardiotoxicity by addressing the main critical points and current evidence related to the assessment, management, treatment, and surveillance of cancer patients under chemotherapy.

Incidence of morbidity and mortality in a cohort of congenital complete heart block patients followed over 40 years.

Congenital complete heart block (CCHB) is seen in 1:15,000-20,000 births and commonly requires pacemaker placement by young adulthood. There is limited understanding of cardiac morbidity and mortality. The purpose of this study was to determine the long-term incidence of cardiac morbidity and mortality in subjects with CCHB and identify associated risk factors. Retrospective cohort analysis of subjects with CCHB at Children's Hospital of Philadelphia between 1976 and 2018 was performed. The primary outcome was a composite of death, left ventricular systolic dysfunction, heart failure, cardiomyopathy, or cardiac resynchronization therapy (CRT). Cox proportional hazard models assessed independent risk factors for the primary outcome and its components (death, heart failure and/or cardiomyopathy, CRT). One-hundred fourteen subjects (58% female; median age at last visit 15.2 years) were included. Eighty-eight (77%) underwent pacemaker implantation (median age at placement 1.9 years; interquartile range [IQR] 0.1-8.0 years). Twenty-six subjects (23%) reached the primary outcome; 7 (6%) died and 14 (12%) were diagnosed with heart failure and/or cardiomyopathy. Median time from diagnosis to primary outcome was 3.1 years (IQR 0.0-10.8 years). There were no significant associations between age at diagnosis <1 year (hazard ratio [HR] 1.5; 95% confidence interval [CI] 0.6-3.9), fetal diagnosis (HR 2.3; 95% CI 0.96-5.6), or maternal antibody positivity (HR 2.4; 95% CI 0.9-6.6) and the primary outcome. Fetal diagnosis had a higher associated hazard of heart failure and/or cardiomyopathy (HR 4.5; 95% CI 1.3-15.0). In 114 subjects with CCHB, 23% reached the composite outcome of cardiac morbidity and mortality, with no significant association between age at diagnosis, fetal diagnosis, and maternal antibody status with composite cardiac morbidity and mortality.

Insights from the use of erythropoietin in experimental Chagas disease

In addition to the long-established role in erythropoiesis, erythropoietin (Epo) has protective functions in a variety of tissues, including the heart. This is the most affected organ in chronic Chagas disease, caused by the protozoan Trypanosoma cruzi. Despite seven million people being infected with T. cruzi worldwide, there is no effective treatment preventing the disease progression to the chronic phase when the pathological involvement of the heart is often observed. Chronic chagasic cardiomyopathy has a wide variety of manifestations, like left ventricular systolic dysfunction, dilated cardiomyopathy, and heart failure. Since Epo may help maintain cardiac function by reducing myocardial necrosis, inflammation, and fibrosis, this study aimed to evaluate whether the Epo has positive effects on experimental Chagas disease. For that, we assessed the earlier (acute phase) and also the later (chronic phase) use of Epo in infected C57BL/6 mice. Blood cell count, biochemical parameters, parasitic load, and echocardiography data were evaluated. In addition, histopathological analysis was carried out. Our data showed that Epo had no trypanocide effect nor did it modify the production of anti-T. cruzi antibodies. Epo-treated groups exhibited parasitic burden much lower in the heart compared to blood. No pattern of hematological changes was observed combining infection with treatment with Epo. Chronic Epo administration reduced CK-MB serum activity from d0 to d180, irrespectively of T. cruzi infection. Likewise, echocardiography and histological results indicate that Epo treatment is more effective in the chronic phase of experimental Chagas disease. Since treatment is one of the greatest challenges of Chagas disease, alternative therapies should be investigated, including Epo combined with benznidazole.

PCI in Patients With Heart Failure: Current Evidence, Impact of Complete Revascularization, and Contemporary Techniques to Improve Outcomes

Coronary artery disease (CAD) is the most common cause of left ventricular systolic dysfunction (LVSD) and heart failure (HF). Revascularization with coronary artery bypass grafting (CABG) reduces all-cause mortality compared with medical therapy alone for these patients. Despite this, CABG is performed in a minority of patients with HF, partly due to patient unwillingness or inability to undergo major cardiac surgery and partly due to physician reluctance to refer for surgery due to high operative risk. Percutaneous coronary intervention (PCI) is a less-invasive method of revascularization that has the potential to reduce periprocedural complications compared with CABG in patients with HF. Recent advances in PCI technology and technique have made it realistic to achieve more complete revascularization with PCI in high-risk patients with HF, although no randomized controlled clinical trials (RCTs) of PCI in HF compared with either medical therapy or CABG have been performed. In this review, we discuss the currently available evidence for PCI in HF and the association between the extent of revascularization and clinical outcomes in HF. We also review recent advances in PCI technology and techniques with the potential to improve clinical outcomes in HF. Finally, we discuss emerging clinical trial evidence of revascularization in HF and the large, persistent evidence gaps that should be addressed with future clinical trials of revascularization in HF.

Heart rate variability is associated with left ventricular systolic, diastolic function and incident heart failure in the general population

BackgroundHRV has mostly shown associations with systolic dysfunction and more recently, with diastolic dysfunction in Heart failure (HF) patients. But the role of sympathetic nervous system in changes of left ventricular (LV) systolic and diastolic function and new-onset HF has not been extensively studied.MethodsAmong 3157 men and 4405 women free of HF and atrial fibrillation retrospectively included from the population-based Rotterdam Study, we used linear mixed models to examine associations of RR-interval differences and standard deviation of RR-intervals corrected for heart rate (RMSSDc and SDNNc) with longitudinal changes of LV ejection fraction (LVEF), E/A ratio, left atrial (LA) diameter, E/e’ ratio. Afterwards, using cox regressions, we examined their association with new-onset HF.ResultsMean (SD) age was 65 (9.95) in men and 65.7 (10.2) in women. Every unit increase in log RMSSDc was accompanied by 0.75% (95%CI:-1.11%;-0.39%) and 0.31% (− 0.60%;-0.01%) lower LVEF among men and women each year, respectively. Higher log RMSSDc was linked to 0.03 (− 0.04;-0.01) and 0.02 (− 0.03;-0.003) lower E/A and also − 1.76 (− 2.77;− 0.75) and − 1.18 (− 1.99;-0.38) lower LVM index in both sexes and 0.72 mm (95% CI: − 1.20;-0.25) smaller LA diameters in women. The associations with LVEF in women diminished after excluding HF cases during the first 3 years of follow-up. During a median follow-up of 8.7 years, hazard ratios (95%CI) for incident HF were 1.34 (1.08;1.65) for log RMSSDc in men and 1.15 (0.93;1.42) in women. SDNNc showed similar associations.ConclusionsIndices of HRV were associated with worse systolic function in men but mainly with improvement in LA size in women. Higher HRV was associated with higher risk of new-onset HF in men. Our findings highlight potential sex differences in autonomic function underlying cardiac dysfunction and heart failure in the general population.

Prognostic relevance of magnesium alterations in patients with a myocardial infarction and left ventricular dysfunction: insights from the EPHESUS trial.

Magnesium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). The relation between serum magnesium and clinical outcomes is insufficiently elucidated in this population. The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hypomagnesemia and hypermagnesemia were defined as a serum magnesium <0.66 and >1.10 mmol/L, respectively. Linear mixed models and time-dependent Cox regression analysis were used to determine the effect of eplerenone on magnesium changes and the prognostic importance of magnesium. The co-primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV hospitalization. A total of 5371 patients had a post-baseline magnesium measurement. At baseline, 231 (4.3%) patients had hypomagnesemia and 271 (5.0%) patients had hypermagnesemia. During a median follow-up of 16 months, 682 (13%) developed hypomagnesemia and 512 (9.5%) hypermagnesemia. Eplerenone treatment did not result in a different magnesium level during follow-up (P = 0.14). After covariate adjustment hypo- and hypermagnesemia were not associated with a higher risk of CV events. Magnesium levels did not modulate the effect of a high potassium (>5 mmol/L) or low potassium (<4 mmol/L) on the clinical outcome. Baseline magnesium levels did not influence the treatment effect of eplerenone (P-interaction > 0.1 for all primary and secondary endpoints). In patients with MI complicated by LVSD or HF, magnesium alterations were not associated with clinical outcomes nor did they influence the effect of eplerenone. Serum magnesium did not modulate the effect of potassium changes on clinical outcome or the treatment effect of eplerenone. NCT00232180.

The Oxidative Stress and Chronic Inflammatory Process in Chagas Disease: Role of Exosomes and Contributing Genetic Factors

Chagas disease is a neglected tropical disease caused by the flagellated protozoa Trypanosoma cruzi that affects several million people mainly in Latin American countries. Chagas disease has two phases, which are acute and chronic, both separated by an indeterminate time period in which the infected individual is relatively asymptomatic. The acute phase extends for 40-60 days with atypical and mild symptoms; however, about 30% of the infected patients will develop a symptomatic chronic phase, which is characterized by either cardiac, digestive, neurological, or endocrine problems. Cardiomyopathy is the most important and severe result of Chagas disease, which leads to left ventricular systolic dysfunction, heart failure, and sudden cardiac death. Most deaths are due to heart failure (70%) and sudden death (30%) resulting from cardiomyopathy. During the chronic phase, T. cruzi-infected macrophages respond with the production of proinflammatory cytokines and production of superoxide and nitric oxide by the NADPH oxidase 2 (NOX2) and inducible nitric oxide synthase (iNOS) enzymes, respectively. During the chronic phase, myocardial changes are produced as a result of chronic inflammation, oxidative stress, fibrosis, and cell death. The cellular inflammatory response is mainly the result of activation of the NF-κB-dependent pathway, which activates gene expression of inflammatory cytokines, leading to progressive tissue damage. The persisting production of reactive oxygen species (ROS) is the result of mitochondrial dysfunction in the cardiomyocytes. In this review, we will discuss inflammation and oxidative damage which is produced in the heart during the chronic phase of Chagas disease and recent evidence on the role of macrophages and the production of proinflammatory cytokines during the acute phase and the origin of macrophages/monocytes during the chronic phase of Chagas disease. We will also discuss the contributing factors and mechanisms leading to the chronic inflammation of the cardiac tissue during the chronic phase of the disease as well as the innate and adaptive host immune response. The contribution of genetic factors to the progression of the chronic inflammatory cardiomyopathy of chronic Chagas disease is also discussed. The secreted extracellular vesicles (exosomes) produced for both T. cruzi and infected host cells can play key roles in the host immune response, and those roles are described. Lastly, we describe potential treatments to attenuate the chronic inflammation of the cardiac tissue, designed to improve heart function in chagasic patients.

Left Ventricular Diastolic Function Following Anthracycline-Based Chemotherapy in Patients with Breast Cancer without Previous Cardiac Disease-A Meta-Analysis.

Background: Anthracycline-based chemotherapy (ANT) remains among the most effective therapies for breast cancer. Cardiotoxicity from ANT represents a severe adverse event and may predominantly manifest as heart failure. While it is well-recognised that left ventricular systolic heart failure assessment is key in ANT-treated patients, less is known about the relevance of LV diastolic functional impairment and its characterisation. Methods: Studies reporting on echocardiographic diastolic function parameters before and after ANT in breast cancer patients without cardiac disease were included. We evaluated pulsed wave (E/A ratio and mitral E-wave deceleration time (EDT)) and tissue Doppler (mean velocities of the mitral ring in the early diastole (e′) and E/e′ ratio) echocardiographic parameters. Results: A total of 892 patients from 13 studies were included. E/A ratio was significantly reduced at the end of ANT while EDT was not influenced by ANT. Additionally, e’ and E/e’ ratio showed no significant change after ANT. A modest reduction in LV ejection fraction and global longitudinal strain was observed at the end of ANT therapy. Conclusions: ANT had a modest early impact on E/A ratio, without changing EDT, e’, or E/e’ in patients with breast cancer without cardiac disease. Randomised studies on larger populations, using new parameters are required to define the role of diastolic dysfunction in the early diagnosis of ANT-induced cardiotoxicity.

Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were eplerenone exhibits some of its pleotropic effects. Little is known about the effect of eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF. The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium < 135mmol/L or > 145mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization. A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to eplerenone had a lower mean serum sodium over the follow-up (140 vs 141mmol/L; p < 0.0001) and more often developed hyponatremia episodes (15 vs 11% p = 0.0001) and less often hypernatremia episodes (22 vs. 26% p = 0.0003). Hyponatremia, but not hypernatremia was associated with adverse outcome for all outcome endpoints in the placebo group but not in the eplerenone group (interaction p value < 0.05 for all). Baseline sodium values did not influence the treatment effect of eplerenone in reducing the various endpoints (interaction p value > 0.05 for all). Development of new-onset hyponatremia following eplerenone initiation did not diminish the beneficial eplerenone treatment effect. Eplerenone induces minor reductions in serum sodium. The beneficial effect of eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing eplerenone to patients who had an MI complicated with LVSD and/or HF. ClinicalTrials.gov identifier: NCT00232180. Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

Systemic tPA Treatment for Thrombosis in a Patient with Dilated Cardiomyopathy on Berlin Heart

Introduction ite advances in anticoagulation management in pediatric VAD, thrombosis and stroke remain a major concern. For patients with thrombosis who fail intensification of standard anticoagulation options are limited. We present a case of thrombosis in a patient on Berlin Heart LVAD that was successfully treated with systemic alteplase. Case Report The patient is a 2 year old 13.6 kg girl (BSA 0.58) with dilated cardiomyopathy and left ventricular systolic heart failure necessitating placement of a Berlin Heart EXCOR LVAD as a bridge to heart transplantation. She was implanted with a 15mL pump at a rate of 100 beats/min. There were no intra-operative complications and anticoagulation was initiated with bivalirudin; target PTT 70-90 sec (achieved consistently by POD#3). On POD#5 she became febrile with rising inflammatory markers and broad spectrum antibiotic therapy was initiated. She then required escalating doses of bivalirudin for decreasing PTT values. After negative blood cultures for 24 hours, she completed a course of pulse steroids for possible inflammatory reaction on the pump. She was also started on aspirin and then dipyridamole. By POD#15, she had an escalating respiratory support requirement in the setting of a large pleural effusion and bivalirudin was held briefly for placement of a chest tube. Despite no obvious fibrin or clot in the device or cannulas, an echocardiogram a revealed a 5mm thrombus in the left ventricle adjacent to the inflow cannula. Given the position of the thrombus, clot extraction by surgical or cardiac catheterization was deemed not feasible due to limited ability to perform thrombectomy without embolization. Therefore, we treated medically with systemic alteplase while maintaining the patient on continuous bivalirudin infusion at lower PTTs. We achieved successful resolution of the thrombus by echocardiogram with no significant complications or neurologic deficits. The patient was supported by the Berlin Heart for 5 months until transplant with no other complications. On evaluation of the explanted heart there was no residual thrombus. A head CT performed after heart transplant for follow up of an unrelated concern revealed no evidence of intracranial hemorrhage or infarct. Summary Systemic tPA may be considered as a treatment option in patients with thrombosis on ventricular assist device in lieu of more invasive treatment options.

Cardiotoxic effects of angiogenesis inhibitors.

The development of new therapies for cancer has led to dramatic improvements in survivorship. Angiogenesis inhibitors represent one such advancement, revolutionising treatment for a wide range of malignancies. However, these drugs are associated with cardiovascular toxicities which can impact optimal cancer treatment in the short-term and may lead to increased morbidity and mortality in the longer term. Vascular endothelial growth factor inhibitors (VEGFIs) are associated with hypertension, left ventricular systolic dysfunction (LVSD) and heart failure as well as arterial and venous thromboembolism, QTc interval prolongation and arrhythmia. The mechanisms behind the development of VEGFI-associated LVSD and heart failure likely involve the combination of a number of myocardial insults. These include direct myocardial effects, as well as secondary toxicity via coronary or peripheral vascular damage. Cardiac toxicity may result from the ‘on-target’ effects of VEGF inhibition or ‘off-target’ effects resulting from inhibition of other tyrosine kinases. Similar mechanisms may be involved in the development of VEGFI-associated right ventricular (RV) dysfunction. Some VEGFIs can be associated with QTc interval prolongation and an increased risk of ventricular and atrial arrhythmia. Further pre-clinical and clinical studies and trials are needed to better understand the impact of VEGFI on the cardiovascular system. Once mechanisms are elucidated, therapies can be investigated in clinical trials and surveillance strategies for identifying VEGFI-associated cardiovascular complications can be developed.