Search

IntroductionRenal failure associated aortic valve calcification (AVC) is the result of hyperphosphatemia and hyperparathyroidism. Calcimimetics is an effective tool for management of secondary hyperparathyroidism. Our goal was to evaluate the effect of the medical intervention with calcimimetic R568 on the AVC process.Methods and resultsThe experimental design consisted of administering a uremia-inducing phosphate-enriched diet to rats for six weeks. Rats received a daily R568 injection at different times. Biochemical analysis demonstrated increased urea (34.72 ± 3.57 vs. 5.18 ± 0.15 mmol/L, p

IntroductionPreformed antibodies against αGal in the human and the presence of αGal antigens on the tissue constituting the commercial bioprosthetic heart valves (BHVs, mainly bovine or porcine pericardium), lead to opsonization of the implanted BHV, leading to deterioration and calcification. Murine subcutaneous implantation of BHVs leaflets has been widely used for testing the efficacy of anti-calcification treatments. Unfortunately, commercial BHVs leaflets implanted into a murine model will not be able to elicit an αGal immune response because such antigen is expressed in the recipient and therefore immunologically tolerated.MethodsThis study evaluates the calcium deposition on commercial BHV using a new humanized murine αGal knockout (KO) animal model. Furtherly, the anti-calcification efficacy of a polyphenol-based treatment was deeply investigated. By using CRISPR/Cas9 approach an αGal KO mouse was created and adopted for the evaluation of the calcific propensity of original and polyphenols treated BHV by subcutaneous implantation. The calcium quantification was carried out by plasma analysis; the immune response evaluation was performed by histology and immunological assays. Anti-αGal antibodies level in KO mice increases at least double after 2 months of implantation of original commercial BHV compared to WT mice, conversely, the polyphenols-based treatment seems to effectively mask the antigen to the KO mice’s immune system.ResultsCommercial leaflets explanted after 1 month from KO mice showed a four-time increased calcium deposition than what was observed on that explanted from WT. Polyphenol treatment prevents calcium deposition by over 99% in both KO and WT animals. The implantation of commercial BHV leaflets significantly stimulates the KO mouse immune system resulting in massive production of anti-Gal antibodies and the exacerbation of the αGal-related calcific effect if compared with the WT mouse. DiscussionThe polyphenol-based treatment applied in this investigation showed an unexpected ability to inhibit the recognition of BHV xenoantigens by circulating antibodies almost completely preventing calcific depositions compared to the untreated counterpart.

Abstract Aims This study aimed to assess the ability of a voice analysis application to discriminate between wet and dry states in chronic heart failure (CHF) patients undergoing regular scheduled haemodialysis treatment due to volume overload as a result of their chronic renal failure. Methods and results In this single‐centre, observational study, five patients with CHF, peripheral oedema of ≥2, and pulmonary congestion‐related dyspnoea, undergoing haemodialysis three times per week, recorded five sentences into a standard smartphone/tablet before and after haemodialysis. Recordings were provided that same noon/early evening and the next morning and evening. Patient weight was measured at the hospital before and after each haemodialysis session. Recordings were analysed by a smartphone application (app) algorithm, to compare speech measures (SMs) of utterances collected over time. On average, patients provided recordings throughout 25.8 ± 3.9 dialysis treatment cycles, resulting in a total of 472 recordings. Weight changes of 1.95 ± 0.64 kg were documented during cycles. Median baseline SM prior to dialysis was 0.87 ± 0.17, and rose to 1.07 ± 0.15 following the end of the dialysis session, at noon (P = 0.0355), and remained at a similar level until the following morning (P = 0.007). By the evening of the day following dialysis, SMs returned to baseline levels (0.88 ± 0.19). Changes in patient weight immediately after dialysis positively correlated with SM changes, with the strongest correlation measured the evening of the dialysis day [slope: −0.40 ± 0.15 (95% confidence interval: −0.71 to −0.10), P = 0.0096]. Conclusions The fluid‐controlled haemodialysis model demonstrated the ability of the app algorithm to identify cyclic changes in SMs, which reflected bodily fluid levels. The voice analysis platform bears considerable potential as a harbinger of impending fluid overload in a range of clinical scenarios, which will enhance monitoring and triage efforts, ultimately optimizing remote CHF management.

Abstract Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be ‘silent’ or ‘asymptomatic’, but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit.

Heart failure (HF) is associated with considerable mortality. The electrocardiographic frontal QRS-T angle is a simple parameter to measure, reflects changes in the direction of the repolarization sequence and predicts outcome in patients with HF. Data regarding temporal changes in the frontal QRS-T angle in patients with HF and its impact on outcome is limited.To evaluate temporal changes in the frontal QRS-T angle and its effect on survival in patients with HF.Baseline and follow-up QRS-T angle were calculated from the frontal QRS and T axis of the 12-lead surface electrocardiogram. Patients were followed for survival.2,929 HF patients were evaluated. Median interval between baseline ECG and follow-up ECG was 895 days, median follow-up time was 1526 days. Overall, the QRS-T angle tended to be stable, with minor changes in the angle over time. The median QRS-T angle change was +3° (IQR -19° to +30°). Overall survival during follow-up was 60%. Cox regression analysis after adjustment for significant predictors demonstrated that the QRS-T angle was an incremental predictor of increased mortality. A widening of the QRS-T angle during follow-up was independently associated with an increase in mortality, evident with an increase of the QRS-T angle difference above 0° (P

Exercise is considered a valuable nonpharmacological intervention modality in cardiac rehabilitation (CR) programs in patients with ischemic heart disease. The effect of aerobic interval exercise combined with alternating sets of resistance training (super-circuit training, SCT) on cardiac patients' with reduced left ventricular function, post-myocardial infarction (MI) has not been thoroughly investigated.to improve cardiac function with a novel method of combined aerobic-resistance circuit training in a randomized control trial by way of comparing the effectiveness of continuous aerobic training (CAT) to SCT on mechanical cardiac function. Secondary to compare their effect on aerobic fitness, manual strength, and quality of life in men post MI. Finally, to evaluate the safety and feasibility of SCT.29 men post-MI participants were randomly assigned to either 12-weeks of CAT (n = 15) or SCT (n = 14). Both groups, CAT and SCT exercised at 60%-70% and 75-85% of their heart rate reserve, respectively. The SCT group also engaged in intermittently combined resistance training. Primary outcome measure was echocardiography. Secondary outcome measures were aerobic fitness, strength, and quality of life (QoL). The effectiveness of the two training programs was examined via paired t-tests and Cohen's d effect size (ES).Post-training, only the SCT group presented significant changes in echocardiography (a reduction in E/e' and an increase in ejection fraction, P

[This corrects the article DOI: 10.1371/journal.pone.0188551.].

BackgroundModerate exercise training has been shown to decrease sudden cardiac death post myocardial infarction. However, the effects of intensive exercise are still controversial. Methods and ResultsFourteen myocardial‐infarcted rats were divided into sedentary (n=8) and intensive training groups (n=6) and 18 sham control rats to sedentary (n=10) and intensive training groups (n=8). Heart rate variability was obtained at weeks 1 and 8. The inducibility of ventricular tachycardia/fibrillation was assessed in a Langendorff system. Fast Fourier transforms were applied on the recorded ventricular tachycardia/fibrillations. Training reduces low to high frequency ratio of heart rate variability at week 8 compared with that at week 1 (P

BackgroundWe investigated national trends in volume and outcomes of percutaneous coronary angioplasty (PCI), coronary artery bypass grafting (CABG), and ischemic heart disease–related mortality in Israel. Methods and ResultsUsing International Classification of Diseases 9th and 10th revision codes, we linked 5 Israeli national databases, including the Israel Center for Disease Control National PCI and CABG Registries, the Ministry of Health Hospitalization Report, the Center of Bureau of Statistics, and the Ministry of Interior Mortality Report, to assess the annual PCI and CABG volume, procedural mortality, comorbidities, and ischemic heart disease‐related mortality between 2002 and 2014. Trends over time were analyzed using linear regression, assuming a Poisson distribution. A total of 298 390 revascularization procedures (PCI: 255 724, CABG: 42 666) were performed during the study period. PCI volume increased by 9% from 2002 to 2008 (387.4/100 000 to 423.2/100 000), steadily decreasing by 10.5% to 378.5/100 000 in 2014 (P=0.70 for the trend). CABG volume decreased by 59% (109.0/100 000 to 45.2/100 000) from 2002 to 2013, leveling at 46.4/100 000 (P

High precision is necessary during percutaneous transcatheter heart valve implantation. The precision of the implantation has been established by increasing the heart rate (usually to 200 beats per minute) to the point of significantly reduced cardiac output and thus minimizing valve movement. Routinely, this tachycardia is induced by rapid pacing. Here we report a case of failure to pace during valve-in-valve (VIV) Edwards Sapien XT implantation in the tricuspid valve position. Transient cardiac arrest was induced by intravenous adenosine injection enabling accurate valve implantation.

FUNDAMENTO: Diferenças entre regiões geográficas em relação à características de pacientes e desfechos, particularmente em síndromes coronarianas agudas, tem sido demonstradas em testes clínicos. Os desfechos clínicos após intervenções coronarianas percutâneas com o stent eluidor de Zotarolimus em uma população real foram analisados com o tempo. OBJETIVO: A influência da localização geográfica sobre os desfechos clínicos com o stent eluidor de Zotarolimus foi avaliada em três regiões: Pacífico Asiático, Europa e América Latina. MÉTODOS: Um total de 8.314 pacientes (6.572 da Europa, 1.522 do Pacífico Asiático e 220 da América Latina) foram acompanhados por 1 ano; 2.116 desses (1.613, 316, e 187, respectivamente) foram acompanhados por 2 anos. Características dos pacientes e lesões, terapia antiplaquetária dupla e desfechos clínicos foram comparados entre a América Latina e as outras duas regiões. RESULTADOS: Os pacientes da América Latina apresentavam a maior proporção de fatores de risco e infarto do miocárdio prévio. O uso da terapia antiplaquetária dupla declinou rapidamente na América Latina, de 44,9% em 6 meses para 22,5% em 1 ano e 7,8% em 2 anos (Europa: 87,4%, 61,5%, 19,7%; Pacífico Asiático: 82,4%, 67,0%, 45,7%, respectivamente). Não houve diferenças significantes entre a América Latina e a Europa ou Pacífico Asiático para qualquer desfecho em qualquer ponto do tempo. A incidência de trombose de stent provável e definitiva pelo Academic Research Consortium foi baixa (FUNDAMENTO: Las diferencias entre las regiones geográficas en relación con las características de pacientes y desenlaces, sobre todo en los síndromes coronarios agudos se ha demostrado en ensayos clínicos. Los desenlaces clínicos después de las intervenciones coronarias percutáneas con stent liberador de zotarolimus en una población real se analizaron a través del tiempo. Objetivos: La influencia de la ubicación geográfica sobre los desenlaces clínicos con el stent liberador de zotarolimus se evaluó en tres regiones: Pacífico Asiático, Europa y América Latina. MÉTODOS: A total of 8,314 patients (6.572 Europe, 1.522 Asia Pacific, and 220 Latin America) were followed for 1 year; 2.116 of these (1.613, 316, and 187, respectively) were followed for 2 years. Patient and lesion characteristics, dual antiplatelet therapy, and clinical outcomes were compared between Latin America and the other regions. RESULTADOS: Los pacientes en América Latina tuvieron la mayor proporción de factores de riesgo e infarto de miocardio previo. Hubo un rápido descenso en el uso de la terapia antiplaquetaria en América Latina, el 44,9% en 6 meses para 22,5% en 1 año y 7,8% en 2 años (Europa: un 87,4%, un 61,5%, un 19,7%; Pacífico Asiático: un 82,4%, un 67,0%, un 45,7%, respectivamente). No hubo diferencias significativas entre América Latina y Europa o Pacífico Asiático para cualquier desenlace en cualquier momento. La incidencia de trombosis de stent probable y definitiva por el Academic Research Consortium fue baja (< 1,2%) entre todos los pacientes en 1 año y 2 años. CONCLUSIONES: Los desenlaces clínicos fueron comparables entre los pacientes de América Latina y Europa, y América Latina y Pacífico Asiático, pese a los subgrupos clínicos menos favorables en América Latina, perfil de riesgo más elevado y menor uso acentuado de terapia antiplaquetaria doble con el tiempo. (Arq Bras Cardiol 2011;96(5):353-362)BACKGROUND: Differences between geographic regions in patient characteristics and outcomes, particularly for acute coronary syndromes, have been demonstrated in clinical trials. Clinical outcomes after percutaneous coronary interventions with the Zotarolimus-eluting stent in a real-world population were assessed over time. OBJECTIVE: The influence of geographic location on clinical outcomes with the Zotarolimus-eluting stent was assessed in 3 regions: Asia Pacific, Europe, and Latin America. METHODS: A total of 8,314 patients (6,572 Europe, 1,522 Asia Pacific, and 220 Latin America) were followed for 1 year; 2,116 of these (1,613, 316, and 187, respectively) were followed for 2 years. Patient and lesion characteristics, dual antiplatelet therapy, and clinical outcomes were compared between Latin America and the other regions. RESULTS: Patients in Latin America had the highest proportions of risk factors and prior myocardial infarction. Dual antiplatelet therapy usage rapidly declined in Latin America, from 44.9% at 6 months to 22.5% at 1 year and 7.8% at 2 years (Europe: 87.4%, 61.5%, 19.7%; Asia Pacific: 82.4%, 67.0%, 45.7%). There were no significant differences between Latin America and Europe or Asia Pacific for any outcome at either time point. The incidence of Academic Research Consortium definite and probable stent thrombosis was low (

BackgroundAortic valve calcification (AVC) secondary to renal failure (RF) is an inflammation-regulated process, but its pathogenesis remains unknown. We sought to assess the cellular processes that are involved in the early phases of aortic valve disease using a unique animal model of RF-associated AVC.MethodsAortic valves were obtained from rats that were fed a uremia-inducing diet exclusively for 2, 3, 4, 5, and 6 weeks as well as from controls. Pathological examination of the valves included histological characterization, von Kossa staining, and antigen expression analyses.ResultsAfter 2 weeks, we noted a significant increase in urea and creatinine levels, reflecting RF. RF parameters exacerbated until the Week 5 and plateaued. Whereas no histological changes or calcification was observed in the valves of any study group, macrophage accumulation became apparent as early as 2 weeks after the diet was started and rose after 3 weeks. By western blot, osteoblast markers were expressed after 2 weeks on the diet and decreased after 6 weeks. Collagen 3 was up-regulated after 3 weeks, plateauing at 4 weeks, whereas collagen 1 levels peaked at 2 and 4 weeks. Fibronectin levels increased gradually until Week 5 and decreased at 6 weeks. We observed early activation of the ERK pathway, whereas other pathways remained unchanged.ConclusionsWe concluded that RF induces dramatic changes at the cellular level, including macrophage accumulation, activation of cell signaling pathway and extracellular matrix modification. These changes precede valve calcification and may increase propensity for calcification, and have to be investigated further.

Myocarditis consists of an inflammation of the cardiac muscle, definitively diagnosed by endomyocardial biopsy. The causal agents are primarily infectious: in developed countries, viruses appear to be the main cause, whereas in developing countries rheumatic carditis, Chagas disease, and HIV are frequent causes. Furthermore, myocarditis can be indirectly induced by an infectious agent and occurs following a latency period during which antibodies are created. Typically, myocarditis observed in rheumatic fever related to group A streptococcal (GAS) infection occurs after 2- to 3-week period of latency. In other instances, myocarditis can occur within few days following a streptococcal infection; thus, it does not fit the criteria for rheumatic fever. Myocarditis classically presents as acute heart failure, and can also be manifested by tachyarrhythmia or chest pain. Likewise, GAS-related myocarditis reportedly mimics myocardial infarction (MI) with typical chest pain, electrocardiograph changes, and troponin elevation. Here we describe a case of recurrent myocarditis, 5 years apart, with clinical presentation imitating an acute MI in an otherwise healthy 37-year-old man. Both episodes occurred 3 days after GAS pharyngitis and resolved quickly following medical treatment.

There is strong evidence supporting the claim that endogenous cardiac progenitor cells (CPCs) are key players in cardiac regeneration, but the anatomic source and phenotype of the master cardiac progenitors remains uncertain. Our aim was to investigate the different cardiac stem cell populations in the left atrial appendage (LAA) and their fates.We investigated the CPC content and profile of adult murine LAAs using immunohistochemistry and flow cytometry. We demonstrate that the LAA contains a large number of CPCs relative to other areas of the heart, representing over 20% of the total cell number. We grew two distinct CPC populations from the LAA by varying the degree of proteolysis. These differed by their histological location, surface marker profiles and growth dynamics. Specifically, CD45(pos) cells grew with milder proteolysis, while CD45(neg) cells grew mainly with more intense proteolysis. Both cell types could be induced to differentiate into cells with cardiomyocyte markers and organelles, albeit by different protocols. Many CD45(pos) cells expressed CD45 initially and rapidly lost its expression while differentiating.Our results demonstrate that the left atrial appendage plays a role as a reservoir of multiple types of progenitor cells in murine adult hearts. Two different types of CPCs were isolated, differing in their epicardial-myocardial localization. Considering studies demonstrating layer-specific origins of different cardiac progenitor cells, our findings may shed light on possible pathways to study and utilize the diversity of endogenous progenitor cells in the adult heart.

The mechanisms whereby aerobic training reduces the occurrence of sudden cardiac death in humans are not clear. We test the hypothesis that exercise-induced increased resistance to ventricular tachycardia and fibrillation (VT/VF) involve an intrinsic remodeling in healthy hearts.Thirty rats were divided into a sedentary (CTRL, n = 16) and two exercise groups: short- (4 weeks, ST, n = 7) and long-term (8 weeks, LT, n = 7) trained groups. Following the exercise program hearts were isolated and studied in a Langendorff perfusion system. An S1-S2 pacing protocol was applied at the right ventricle to determine inducibility of VT/VF. Fast Fourier transforms were applied on ECG time-series. In-vivo measurements showed training-induced increase in aerobic capacity, heart-to-body weight ratio and a 50% low-to-high frequency ratio reduction in the heart rate variability (p

BackgroundPatients with heart failure (HF) have a poor prognosis. The proportion of patients with HF and preserved left ventricular function (LVF) is increasing. Long term prognosis of HF with preserved LVF may not be so benign.ObjectivesTo evaluate the long term clinical outcome of patients with HF and preserved LVF and predictors of outcome.MethodsWe prospectively evaluated 309 patients hospitalized with a definite clinical diagnosis of HF. Patients were followed for a mean of 6.5 years for clinical outcome.ResultsMore than a third (36%) of the patients had preserved systolic LVF based on echocardiography. The long term survival rate in this group was poor and not significantly different from patients with reduced LVF (28% vs 23% respectively, P=0.2). The adjusted survival rate by Cox regression analysis was also not significantly different (hazard ratio 1.16, 95% confidence interval 0.87-1.55, P=0.31). The event free survival from death or heart failure re-hospitalization was also low in both groups and not significantly different between patients with preserved vs. reduced LVF (12% vs. 10% respectively, P=0.2). Predictors of mortality in patients with preserved LVF were age, functional capacity and serum urea levels.ConclusionsThe long term clinical outcome of patients with heart failure and preserved LVF is poor and not significantly different from patients with reduced LVF.

BACKGROUND: Endurance exercise may induce transient cardiac dysfunction. Data regarding the effect of caloric restriction on cardiac function is limited. We studied the effect of physical activity performed during extreme caloric deprivation on cardiac function. METHODS: Thirty-nine healthy male soldiers (mean age 20 ± 0.3 years) were studied during a field training exercise lasted 85-103 hours, with negligible food intake and unlimited water supply. Anthropometric measurements, echocardiographic examinations and blood and urine tests were performed before and after the training exercise. RESULTS: Baseline VO(2) max was 59 ± 5.5 ml/kg/min. Participants' mean weight reduction was 5.7 ± 0.9 kg. There was an increase in plasma urea (11.6 ± 2.6 to 15.8 ± 3.8 mmol/L, p

PURPOSE OF REVIEW: This review provides a practical overview of the performance capabilities of automatic external defibrillators (AEDs), and of advances in technology and dissemination programmes for these devices. RECENT FINDINGS: Arrhythmia analysis by AEDs is extremely reliable in most settings (sensitivity 81100%, specificity 99.997.6%). Accurate detection of arrhythmias has also been demonstrated in children, leading the US Food and Drug Administration to approve the use of several AEDs in children aged 8 years or younger. Factors that potentially may reduce the quality of arrhythmia detection are the presence of wide complex supraventricular tachycardia and location of an arryhthmic event near to high-power lines. AED use by professional basic life support providers resulted in increased survival in the prehospital setting. However, provision of AEDs to nonmedical rescue services did not result in universal improvement in patient outcome. Public access defibrillation programmes have led to higher rates of survival from cardiac arrest. The role of AEDs in hospitals has yet to be elucidated, although in-hospital mortality from ventricular arrhythmias has been shown to decrease following AED deployment. SUMMARY: Given the correct setting, AEDs can ensure that defibrillation is not limited by lack of medical knowledge or difficulties in decision making. However, event-related variables and operator-related factors, that are yet to be determined, can significantly affect the efficacy of automatic external defibrillation. [ABSTRACT FROM AUTHOR]