Prevalencia e incidencia de hiperpotasemia en población española con insuficiencia cardiaca con fracción de eyección deprimida: revisión sistemática y relevancia poblacional / Prevalence and incidence of hyperkalaemia in the Spanish population with heart failure with reduced ejection fraction: a systematic review and populational relevance

Antecedentes y objetivo: La hiperpotasemia (K+≥5,5mmol/l) es un desequilibrio iónico grave cuando aparece en pacientes que padecen insuficiencia cardiaca con fracción de eyección deprimida (ICFED), ya que incrementa el riesgo de fibrilación ventricular. No existen estimaciones del número de pacientes que sufren esta complicación. El objetivo de este estudio fue estimar la prevalencia e incidencia de hiperpotasemia en pacientes con ICFED en España. Materiales y métodos: A partir de una búsqueda bibliográfica sistemática se calculó mediante un metaanálisis la prevalencia de ICFED<40% en población europea y norteamericana. A partir de otra búsqueda bibliográfica sistemática se calculó la prevalencia de hiperpotasemia en individuos con insuficiencia cardiaca, así como su incidencia anual. Considerando los anteriores valores y la pirámide de población española en 2016 se estimó el número de individuos con ICFED que presentan actualmente y que desarrollan cada año hiperpotasemia en España. Resultados: Alrededor de 17.100 individuos (10.000 hombres y 7.100 mujeres) de los 508.000 pacientes con ICFED presentan hiperpotasemia en España. Asimismo, unos 14.900 pacientes con ICFED (9.500 hombres y 5.400 mujeres) la desarrollan cada año. Conclusiones: Aproximadamente uno de cada 30 pacientes con ICFED presenta valores plasmáticos de potasio por encima de 5,5mmol/l

Background and objectives: Hyperkalaemia (K+ levels≥5.5mmol/L) is a severe ion imbalance that occurs in patients who have heart failure (HF) with reduced ejection fraction (HFrEF) and increases the risk of ventricular fibrillation. Given that there are no estimates on the number of patients with this complication, the aim of this study was to estimate the prevalence and incidence of hyperkalaemia in patients with HFrEF in Spain. Material and methods: Based on a systematic literature search and through a meta-analysis, we calculated an HFrEF prevalence of ≤40% in the European and U.S. population. Based on another systematic literature search, we calculated the prevalence of hyperkalaemia in patients with HF and its annual incidence rate. Considering the previous values and the Spanish population pyramid in 2016, we estimated the number of individuals with HFrEF who currently have hyperkalaemia and those who develop it each year in Spain. Results: Approximately 17,100 (10,000 men and 7100 women) of the 508,000 patients with HFrEF in Spain have hyperkalaemia. Furthermore, approximately 14,900 patients with HFrEF (9500 men and 5400 women) develop hyperkalaemia each year. Conclusions: Approximately 1 of every 30 patients with HFrEF has plasma potassium values >5.5 mmol/L

Prevalence and incidence of hyperkalaemia in the Spanish population with heart failure with reduced ejection fraction: a systematic review and populational relevance. / Prevalencia e incidencia de hiperpotasemia en población española con insuficiencia cardiaca con fracción de eyección deprimida: revisión sistemática y relevancia poblacional.

BACKGROUND AND OBJECTIVES: Hyperkalaemia (K+ levels≥5.5mmol/L) is a severe ion imbalance that occurs in patients who have heart failure (HF) with reduced ejection fraction (HFrEF) and increases the risk of ventricular fibrillation. Given that there are no estimates on the number of patients with this complication, the aim of this study was to estimate the prevalence and incidence of hyperkalaemia in patients with HFrEF in Spain. MATERIAL AND METHODS: Based on a systematic literature search and through a meta-analysis, we calculated an HFrEF prevalence of ≤40% in the European and U.S. POPULATION: Based on another systematic literature search, we calculated the prevalence of hyperkalaemia in patients with HF and its annual incidence rate. Considering the previous values and the Spanish population pyramid in 2016, we estimated the number of individuals with HFrEF who currently have hyperkalaemia and those who develop it each year in Spain. RESULTS: Approximately 17,100 (10,000 men and 7100 women) of the 508,000 patients with HFrEF in Spain have hyperkalaemia. Furthermore, approximately 14,900 patients with HFrEF (9500 men and 5400 women) develop hyperkalaemia each year. CONCLUSIONS: Approximately 1 of every 30 patients with HFrEF has plasma potassium values >5.5 mmol/L.

Role of Vascular Disease in the Evolution of Heart Transplant Patients.

BACKGROUND: The clinical profile of heart transplantation (HT) recipients has changed in recent years. Nowadays, we have to deal with a higher number of co-morbidities, including peripheral vascular disease (PVD). Previous studies suggest an increase in post-HT morbidity and mortality associated with PVD, especially when it is symptomatic. Our study aims were to analyze the prognostic implications of the presence of PVD before transplantation and to determine the factors associated with its development after it. METHODS: HT patients (n = 217) who survived the first year after surgery were included in the study. Mean follow-up was 9 ± 5 years. RESULTS: There were no statistically significant differences in mortality rates between patients with PVD (before or after HT) and those without. One third of patients with PVD required surgery in the post-HT monitoring, either revascularization or amputation. Furthermore, the prevalence of PVD was doubled. Dyslipidemia before HT (odds ratio [OR]: 2.9, 95% confidence interval [CI]: 1.3-6.4; P < .01) and older recipient age (OR: 1.05, 95% CI: 1.01-1.09; P < .05) were independently associated with development of PVD by means of multivariate analysis. CONCLUSIONS: The presence of PVD must be evaluated individually in candidates for heart transplantation despite being a relative contraindication to it at the present time.

A new measuring and identification approach for time-varying bioimpedance using multisine electrical impedance spectroscopy.

The bioimpedance measurement/identification of time-varying biological systems Z(ω, t) by means of electrical impedance spectroscopy (EIS) is still a challenge today. This paper presents a novel measurement and identification approach, the so-called parametric-in-time approach, valid for time-varying (bio-)impedance systems with a (quasi) periodic character. The technique is based on multisine EIS. Contrary to the widely used nonparametric-in-time strategy, the (bio-)impedance Z(ω, t) is assumed to be time-variant during the measurement interval. Therefore, time-varying spectral analysis tools are required. This new parametric-in-time measuring/identification technique has experimentally been validated through three independent sets of in situ measurements of in vivo myocardial impedance. We show that the time-varying myocardial impedance Z(ω, t) is dominantly periodically time varying (PTV), denoted as ZPTV(ω, t). From the temporal analysis of ZPTV(ω, t), we demonstrate that it is possible to decompose ZPTV(ω, t) into a(n) (in)finite sum of fundamental (bio-)impedance spectra, the so-called harmonic impedance spectra (HIS) Zk(ω)s with [Formula: see text]. This is similar to the well-known Fourier series of a periodic signal, but now understood at the level of a periodic system's frequency response. The HIS Zk(ω)s for [Formula: see text] actually summarize in the bi-frequency (ω, k) domain all the temporal in-cycle information about the periodic changes of Z(ω, t). For the particular case k = 0 (i.e. on the ω-axis), Z0(ω) reflects the mean in-cycle behavior of the time-varying bioimpedance. Finally, the HIS Zk(ω)s are directly identified from noisy current and voltage myocardium measurements at the multisine measurement frequencies (i.e. nonparametric-in-frequency).

The feasibility of transoesophageal bioimpedance measurements for the detection of heart graft rejection.

Previous studies demonstrate that it is possible to evaluate a heart graft rejection condition using a bioimpedance technique by means of an intracavitary catheter. We propose to use a less invasive technique consisting in the use of a transoesophageal catheter and two standard ECG electrodes on the thorax. The aim of this work is to evaluate, using the finite element method, several parameters affecting the transoesophageal impedance measurement, including sensitivity to electrical conductivity and permittivity of different organs in the thorax, changes in magnitude and phase due to a lesion producing a scar, a global ischaemia of the heart, pleural effusion in the lungs, fat thickness increase, displacement of the catheter inside the oesophagus and movement of one electrode on the thorax surface. From these results, we deduce the best estimator for cardiac rejection detection and obtain the tools to identify eventual cases of false positives due to other factors. To achieve these objectives we have created a thoracic model and we have simulated different situations at the frequencies of 13, 30, 100, 300 and 1000 kHz. Our simulation demonstrates that the phase, at 100 and 300 kHz, would be a better estimator than the magnitude to evaluate a heart rejection condition.

Umbilical cord blood-derived stem cells spontaneously express cardiomyogenic traits.

BACKGROUND: Umbilical cord blood (UCB) has been widely used for hematopoietic stem cell transplantation. The UCB-derived stem cells (UCBSCs) have been proposed as an alternative to bone marrow (BM)-derived mesenchymal stem cells (MSCs) for cardiac cell-based therapy. Herein we studied whether UCBSCs spontaneously exhibit cardiac-specific markers in vitro. METHODS: Human UCBSCs were isolated, expanded, and phenotyped by flow cytometry, quantitative RT-PCR, and immunofluorescence. Cell pluripotency and proliferation were also assessed by adipogenic and osteogenic media and in growth assays. RESULTS: Among 25 analyzed UCB, 16% of cases afforded primary culture satisfactory generation of UCBSCs. Duplication time (Td) of cultures was 2.16 +/- 0.06 days. The cells were strongly positive for CD105 (18.5 +/- 0.14), CD44 (27 +/- 2.8), CD166 (13 +/- 9), CD29 (59 +/- 9.4), CD90 (60 +/- 11) and consistently negative for CD117 (1.2 +/- 0.1), CD106 (1.1 +/- 0), CD34 (1.2 +/- 0.2), CD14 (1 +/- 0), and CD45 (1 +/- 0), consistent with a mesenchymal lineage. Adipogenesis and osteogenesis of cells resulted in low accumulation of intracellular lipid droplets and high deposition of calcium. The UCBSCs showed gene transcripts for alpha-actinin, connexin (Cx)-43, SERCA-2, and stromal cell-derived factor (SDF)-1alpha. At the protein level, the cells abundantly expressed alpha-actinin, Cx-43, SERCA-2 and SDF-1alpha. In contrast, these cells did not express the cardiac transcription factors GATA-4, Tbx5, and Nkx2.5, nor the sarcomeric proteins beta-myosin heavy chain (beta-MyHC) or cardiac troponin I (cTnI). CONCLUSIONS: Human UCBSCs may represent an alternative source of stem cells for myocardial-cell replacement. These cells can be highly expanded. They spontaneously express proteins of paramount importance for cardiovascular regeneration, such as Cx-43, SERCA-2, and SDF-1alpha.

Identification of cardiomyogenic lineage markers in untreated human bone marrow-derived mesenchymal stem cells.

BACKGROUND: Recent reports refute the classic paradigm by which human heart is unable to repair itself following disease or injury. Cardiac and noncardiac stem cells with cardiac regeneration potential have been documented. We studied whether untreated mesenchymal stem cells express markers of cardiomyogenic lineage in vitro. METHODS: Mesenchymal stem cells were obtained from human iliac crest marrow aspirates. Cells were isolated and characterized using flow cytometry by surface expression of CD105, CD166, CD29, CD44, CD14, and CD34. To evaluate their cardiomyogenic potential, presence of cardiac proteins (cardiac troponin I, sarcomeric alpha-actinin, beta myosin heavy chain (beta-MyHC), connexin-43, and SERCA-2), and transcription factors (GATA-4) were assessed. RESULTS: Mesenchymal stem cells expressed CD105 (4.25 +/- 0.35), CD166 (27.83 +/- 1.89), and CD29 (9.4 +/- 0.57) and were negative for CD34, CD14, and CD45. In absence of additional stimuli in the culture media, these cells expressed connexin-43, alpha-actinin, and GATA-4, and were negative for SERCA-2, cardiac troponin I, and beta-MyHC. CONCLUSIONS: Human adult mesenchymal stem cells spontaneously exhibit markers of cardiac phenotype in vitro. In the appropiate myocardial environment, these cells may transdifferentiate into mature cardiomyocytes.

Serological response to Cryptosporidium parvum in adult cattle from the Andean region of Colombia.

Single faecal and serum samples were individually collected from 135 asymptomatic adult cows on seven farms in Cundinamarca (Colombian Andean region). Tests for the presence of oocysts of Cryptosporidium parvum (carbol fuchsin stain) and Eimeria spp (flotation in saturated saline solution) revealed that none of the animals had coccidia in their faeces. The IgG antibody levels to C. parvum were measured by an enzyme-linked immunosorbent assay (ELISA) technique and the reactivity to C. parvum antigens by a Western blotting procedure. Cryptosporidial antibodies were detected in cattle from all farms, with 53.3% (72 animals) being seropositive. Sera recognized 5-11 protein fractions with molecular masses ranging from 12 14 kDa to 97-100 kDa. Sera considered as positive by ELISA reacted intensely and more frequently with protein fractions of approximately 20-22, 42-48, 51-57 and 60-69 kDa, whereas only the 42-48 kDa antigen was strongly recognized by sera without IgG antibodies. The presence of IgG antibody against C. parvum in most animals, as well as the reactivity to major proteins of C. parvum, could be indicative of continuous exposure to this parasite.

Treatment with beta-cyclodextrin of natural Cryptosporidium parvum infections in lambs under field conditions.

Following the unexpected activity of the excipient beta-cyclodextrin against experimental infection by Cryptosporidium parvum in suckling mice, its efficacy in the prevention and treatment of natural infections in lambs was evaluated under field conditions. Fifty-three crossbred neonatal lambs were randomly selected for the study. Treatment consisted of oral administration of an aqueous suspension of beta-cyclodextrin at a dose of 500 mg/kg of body weight. To test prophylactic efficacy, the suspension was administered at 1, 2 and 3 days of age. To evaluate therapeutic efficacy, the suspension was administered on each of the 3 days following onset of diarrhoea. Infection was monitored by daily examination of faecal samples, from birth to 30 days. The criteria studied in evaluating efficacy were: oocyst shedding, the presence of diarrhoea, and weight gain at 15 and 30 days. In the group that received prophylactic treatment with beta-cyclodextrin, there were no mortalities and, compared with control lambs, there was a decrease in the number of animals infected, a longer prepatent period and notable reduction in the patent period and the duration of diarrhoea. Therapeutic treatment also reduced the patent period and the severity of diarrhoea. beta-cyclodextrin was well tolerated by all of the treated animals.

Percutaneous electrocatheter technique for on-line detection of healed transmural myocardial infarction.

Healed myocardial infarction has been recognized by its particular tissue electrical impedance spectrum measured with intramural needle electrodes in animal models. The aim of this study was to develop a percutaneous approach for in vivo recognition of areas of healed myocardial infarction by measuring myocardial electrical impedance with an intracavitary contact electrocatheter. Electrical impedance (resistance and phase angle) of normal myocardium and of a 2-month-old anterior transmural infarction were measured in nine chloralose anesthetized pigs by applying alternating currents from 1 kHz to 1 MHZ between a bipolar intracavitary catheter and a reference electrode placed on the epicardium (group I, n = 4) or on the precordium (group II, n = 5). Resistance of the infarcted myocardium was lower than that of healthy tissue at all current frequencies (ANOVA, P < 0.001) (i.e., at 1 kHz: 15 +/- 4 omega vs 50 +/- 19 omega in group I, and 64 +/- 13 omega vs 76 +/- 13 omega in group II). Phase angle at 316 kHz best differentiated transmural infarction from normal tissue (group I: -2.5 +/- 1.9 degrees vs -14.8 +/- 4.6 degrees, P < 0.001; group II: +0.7 +/- 1.0 degrees vs -2.7 +/- 1.4 degrees, P < 0.001). This study shows that analysis of myocardial impedance spectrum using a percutaneous intracavitary contact catheter approach permits on-line recognition of areas of healed transmural myocardial infarction. This technique may be useful to optimize clinical application of energy sources (i.e., radiofrequency ablation, laser myocardial revascularization).

Neurally mediated depressor hemodynamic response induced by intracoronary catheter balloon inflation in pigs.

OBJECTIVES: To assess whether intracoronary catheter balloon inflation triggers a neurally mediated hemodynamic response that interacts with the ischemia-induced myocardial dysfunction. METHODS: Forty-eight chloralose anesthetized pigs underwent a 60 s intraluminal catheter balloon inflation of the proximal left anterior descending (LAD) coronary artery before and after one of these treatments: disruption of LAD pericoronary nerves with phenol (n=6), bilateral stellectomy (n=8), bilateral cervical vagotomy (n=6), atropine (n=5), and ganglionic blockade with hexamethonium (n=10). In 13 other pigs, we assessed the reproducibility of two balloon inflations spaced 15 min (n=6) or 60 min (n=7). The ECG, left ventricular (LV) pressure, and LV dP/dt were recorded during each intervention. Right ventricular (RV) pressure, RV dP/dt, and aortic blood flow were also measured in a subset of pigs. RESULTS: Balloon inflation induced an early (10 s) and reproducible (ANOVA, P<0.001) drop in systolic pressure and peak dP/dt; a decrease in aortic blood flow; a rise in end-diastolic pressure; and elevation of the ST segment. Pericoronary denervation, stellectomy and ganglionic blockade attenuated (P<0.001) the drop in LV parameters during coronary inflation, but atropine and vagotomy did not. CONCLUSIONS: A depressor hemodynamic response subserved by pericoronary nerves worsens the LV dysfunction induced by brief coronary catheter balloon inflation in anesthetized pigs. Cholinergic fibers do not appear to play a major role.

Cardiovascular reflex responses induced by epicardial chemoreceptor stimulation.

The cardiac mechano- and chemoreceptors are broadly distributed in the myocardium and coronary vessels. A portion of these receptors extends over the epicardium and pericardium and therefore can be excited by mechanical or chemical stimuli directly applied to the surface of the heart. Excitation of epicardial receptors by topical application of chemical compounds elicits a variety of reflex cardiovascular responses, without the vascular or systemic effects of the drug administered systemically. A considerable number of studies has used the epicardial sensory field as a tool to delineate the functional characteristics of the cardiac afferent neurones in normal as well as in pathological conditions. In this review we analyze the cardiovascular reflex responses induced by epicardial application of a variety of substances like bradykinin, nicotine, muscarine, isoprenaline, adenosine, potassium chloride, capsaicin, prostaglandins or substance P in physiological models and also in models with acute myocardial ischemia or heart failure. The data highlight the contribution of the epicardial sensory neurites to the overall control of the cardiovascular system and, on the other hand, strengthen the need for further investigations directed to better elucidate the reflex cardiovascular responses that may develop in patients with pericardial abnormalities.

[Sudden death (II). Myocardial ischemia and ventricular arrhythmias in experimental models: triggering mechanisms]. / Muerte súbita (II). Isquemia miocárdica y arritmias ventriculares en modelos experimentales: mecanismos desencadenantes.

Metabolic and electrolytic alterations generated in the acute ischemic myocardium, such as an increase in extracellular potassium or acidosis, are responsible for the occurrence of ventricular arrhythmias. In the first 5-10 minutes following coronary occlusion, reentry seems to have an important role, although not in the next 15 minutes. If the patient survives, a subacute arrhythmia period appears, 6 to 72 hours after the onset of ischemia, probably due to abnormal automaticity in the surviving Purkinje fibers. Finally, reentry in the epicardial border zone is the most likely mechanism for chronic arrhythmias. In this review we focus on the studies dealing with the mechanisms of ischemia-induced arrhythmias, with special reference to those conducted in experimental models.

In vivo and in situ ischemic tissue characterization using electrical impedance spectroscopy.

The investigation of processes of ischemia in different organ tissues is very important for the development of methods of protection and preservation during surgical procedures. Electrical impedance spectroscopy was used to distinguish between different tissues and their degree of ischemia. We describe mathematical methods used to adjust experimental data to Cole-Cole models for one-circle and two-circle impedance loci and a study of the main parameters for representing the behavior of ischemia in time. In vivo and in situ postmortem measurements of different tissues from pigs are shown in the 100 Hz to 1 MHz range. The Cole parameters that best characterize the ischemia are R0 and fc.

Oocysts, IgG levels and immunoblot patterns determined for Cryptosporidium parvum in bovine examined during a visit to a farm (northeastern Spain).

Single fecal and serum samples were individually collected from 101 bovines selected at random during a visit to a farm in northeastern Spain (Group I, 26 animals aged 2-36 days; Group II, 34 animals aged 1.5-4.5 months; Group III, 41 animals aged 20-24 months). Testing for the presence of Cryptosporidium parvum oocysts in feces (Monofluo Kit Cryptosporidium, Diagnostics Pasteur, France) indicated that 26% animals were infected (81% of Group I, 15% of Group II and 0% of Group III). Serological testing (ELISA for detection of specific anti-C. parvum IgG) indicated that 59% animals were seropositive (12% of Group I, 74% of Group II and 78% of Group III). Immunoblotting results indicate that cattle sera recognize C. parvum antigens of widely varying molecular weights and that the number of antigens recognized increases with age. Immunoblots revealed that some of the sera belonging to the Group I reacted with protein fractions between 15 and 20 kDa but none recognized the 21-23 kDa antigen. Only few sera in the Group II recognized the protein fraction between 15 and 20 kDa. The recognition of 21-23 kDa fraction was observed by four sera from uninfected and seropositive animals. Sera from all the seronegative Group II animals recognized few antigens and always with molecular weight greater than 50 kDa. Serum samples from both seropositive and seronegative animals belonging to the Group III recognized antigens with molecular weight ranging 15-20 kDa. Surprisingly, the protein fractions between 21 and 28 kDa reacted with approximately 30% of the sera from seropositive animals and only one of the nine sera from seronegative animals. The recognition of 42-46 kDa antigens increased with the age and only reacted with the sera from uninfected animals.