Heart failure (HF) is a complex, debilitating disease that affects approximately 6.5 million Americans (Ades et al., 2013). HF is a large reason for hospital readmissions, and subsequently, a major contributor to rising health care costs. Unfortunately, there is no cure for HF, but various interventions such as cardiac rehabilitation (CR) have been employed to help patients manage the symptoms. However, the lack of patients ever being referred to cardiac rehabilitation is disturbing. Healthcare providers play an essential role in providing education about heart failure and CR, and thus should be knowledgeable about these principles themselves. Therefore, the aim of this project is to evaluate data from a survey sent to nurse practitioners (NPs) regarding whether HF patients are being referred to CR appropriately, and if barriers are limiting use of CR programs. This was a descriptive, nonexperimental study with a survey design seeking to understand if NP providers are following evidence-based guidelines when treating HF patients and if providers consider CR programs to be an appropriate treatment tool. A survey questionnaire was distributed to NPs who are members of Coalition of Arizona Nurses in Advanced Practice (CAZNAP). Data from 27 surveys were used for analysis. Results showed that nurse practitioner respondents felt they had a good understanding of heart failure education and diagnosis. A majority also considered CR to be a useful tool for HF patients, and all agreed that health care providers affect CR enrollment and participation rates. A mere nine respondents (33%) reported being introduced to the outcomes and benefits of CR in their graduate education. Findings also confirmed previous work suggesting that providers are not adequately referring HF patients to CR, as 33% of NPs reported they have never referred a patient to CR. With respect to these findings, it is important to identify methods to assist providers with proper education about CR and its referral methods. As supported by the literature review, improved referral rates to CR can lead to better management and health outcomes for HF patients. Therefore, further research is needed to identify interventions that promote increased CR referral rates.

Orientador: Maria Lúcia Gomes Lourenço / Resumo: A doença renal crônica (DRC) é uma alteração com elevada casuística na clínica de pequenos animais, caracterizada por lesão irreversível dos néfrons. Muitos avanços foram realizados na conduta terapêutica do paciente nefropata na clínica de cães e gatos, dentre estes, a instituição da hemodiálise intermitente (HDI), representando um tratamento suporte importante. Em medicina, muitos indicadores relacionados ao risco de mortalidade têm sido explorados, dentre eles a variabilidade da frequência cardíaca (VFC), a dispersão da onda P, bem como a dispersão do intervalo QT já muito estudados, inclusive em pacientes submetidos à hemodiálise. O objetivo do presente estudo consistiu em avaliar a VFC, bem como descrever o perfil arritmogênico de cães portadores de DRC IV submetidos à HDI e compará-los a cães portadores de DRC IV submetidos apenas ao tratamento clínico e a cães saudáveis. Foram utilizados 30 cães, de ambos os sexos, de variadas idades e raças, pesando entre 15 a 30 kg. Os animais foram divididos em três grupos, sendo o grupo I (controle) –com 10 cães saudáveis, grupo II (tratamento clínico) –com 10 cães com DRC em estádio IV, submetidos ao tratamento clínico, duas vezes por semana e grupo III (HDI) –com 10 cães com DRC IV, submetidos, ao tratamento clínico e dialítico, duas vezes por semana. As análises clínicas, laboratoriais, índices de VFC e parâmetros eletrocardiográficos, bem como as dispersões do intervalo QT e onda P foram realizadas nos dois grupos de DRC IV, an... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Chronic kidney disease (CKD) is an alteration with high casuistry in the small animal clinic, characterized by irreversible damage of the nephrons. Many advances have been made in the therapeutic management of the nephropathic patient in the clinic of dogs and cats, among them, the institution of intermittent hemodialysis (IHD), representing an important support treatment. In medicine, many indicators related to mortality risk have been explored, including heart rate variability (HRV), P-wave dispersion, as well as the dispersion of the QT interval already widely studied, including in patients undergoing hemodialysis. The objective of the present study was to evaluate the HRV, as well as to characterize the arrhythmogenic profile of dogs with CKD stage IV undergoing IHD and to compare them to dogs with CKD stage IV submitted only to clinical treatment and to healthy dogs. Thirty dogs of both sexes, of varying ages and races, weighing between 15 and 30 kg were used. The animals were divided into three groups, group I (control) - 10 healthy dogs, group II (clinical treatment) - 10 dogs with CKD IV, submitted to clinical treatment twice a week and group III (IHD) - 10 dogs with CKD IV, submitted, in addition to clinical treatment, to dialysis treatment, with intermittent hemodialysis, twice a week. Clinical, laboratory, HRV indexes and electrocardiographic parameters as well as QT and P-wave dispersions were performed in both CKD groups, prior to and after the end of each clinic... (Complete abstract click electronic access below) / Doutor

Computed Tomography Coronary Angiography (CTCA)is a technique for imaging coronary arteries with increasing indications in clinical cardiology. AIMS 1.Develop a heart rate (HR) lowering regime for CTCA and to measure its association with image quality. 2.Examine the diagnostic accuracy of 64 slice CTCA (CTCA64) in patients with known coronary artery disease (CAD). 3.Examine the diagnostic accuracy of CTCA64 for assessment of stent restenosis 4.Demonstrate utility of CTCA as an endpoint in assessment of novel diagnostic biomarkers of CAD. METHODS I developed a HR reducing strategy using metoprolol and assessed its effectiveness for improving CTCA64 image quality. The diagnostic value of CTCA in patients with suspected angina was evaluated by comparison with invasive coronary angiography. The diagnostic value of CTCA for quantifying stent restenosis was evaluated by comparison with intravascular ultrasound. The utility of CTCA for evaluating the diagnostic value of B-type natriuretic peptide (BNP) and high sensitivity cardiac troponin I (hs- TnI) was evaluated by blood sampling in patients with suspected angina who subsequently underwent CTCA. RESULTS 1.In 121 patients undergoing CTCA, 75 required rate control. This was achieved (rate ≤60 bpm) in 83% using a systematic regimen of oral and IV metoprolol (n=71) or verapamil (n=4). I demonstrated a significant relation between HR reduction and graded image quality (p<0.001). 2.80 patients underwent CTCA64 and invasive coronary angiography. 724 coronary arterial segments were available for analysis. The sensitivity and specificity of CTCA for significant luminal stenosis was 83.3% (95% CI 67.1-92.5%) and 96.7% (95% CI 95.1-97.9%), respectively, but the positive predictive value was only 63.5% (95% CI 50.4-75.3%). 3.80 patients with 125 stented segments underwent CTCA64 and invasive coronary angiography. Additional intravascular ult rasound (IVUS) examination of stented segments was performed in 48 patients. Using IVUS as the gold-standard for stent restenosis, CTCA and invasive coronary angiography had comparable diagnostic specificities for binary stent restenosis: 82.7% (95% confidence intervals 69.7- 91.84%)and 78.9% (95% confidence intervals 65.3-88.9%), respectively. Sensitivities were lower, particularly the sensitivity of CTCA which was only 11.8% (95% confidence intervals 1.5-36.4%) compared with 58.8% (95% confidence intervals 32.9-81.6%) for invasive coronary angiography. 4. In 93 patients with suspected angina CTCA64 provided a useful endpoint for assessing the diagnostic value of novel circulating biomarkers. BNP levels were higher in the 13 patients shown to have significant (≥50% stenosis) coronary artery disease compared with patients who had unobstructed coronary arteries (18.08pg/ml (IQR 22) vs 9.14pg/ml (IQR 12.62), p=0.024) and increased significantly with exercise, particularly in the group with anatomic coronary artery disease (2.73 ± 5.69 pg/ml vs 1.27±3.29 pg/ml, p=0.16). Conversely I found no association between hs-TnI and the presence of CAD. CONCLUSION Image quality of CTCA64 is enhanced by heart rate reduction below 60 bpm which can be achieved safely by a regimen of oral and intravenous metoprolol. Although CTCA64 is a useful non-invasive method for diagnosis of coronary artery disease, it has a low positive predictive value for identifying severe (≥50%) luminal stenosis which limits its clinical value. Its value for assessment of stent restenosis is even more limited but it finds useful application as an endpoint for diagnostic evaluation of novel biomarkers, allowing confirmation of an association between circulating BNP levels and stable coronary artery disease.

Although a rare disease, light chain (LC) amyloidosis (AL) is the most common systemic amyloidosis in developed countries. It is caused by an overproduction of immunoglobulin LC proteins in bone marrow plasma cells. In AL amyloidosis, LCs that are prone to misfolding and insolubility will aggregate, form fibrils, and deposit themselves in various tissues, thereby causing organ dysfunction. The most fatal manifestation of AL amyloidosis is associated with cardiac involvement, defined by the presence of extracellular AL amyloid deposits within the heart. Cardiac amyloid infiltration typically leads to diastolic dysfunction followed by heart failure and has a median survival of approximately 6 months from the time of diagnosis if untreated. Clinical observation suggests that a reduction in circulating LCs results in an improvement in heart failure symptoms despite minimal changes in amyloid deposition. This has led to the concept that LCs themselves are cytotoxic to cardiomyocytes. Recent studies indicate that AL LCs induce oxidative stress, cellular dysfunction, and apoptosis (programmed cell death) in cardiomyocytes via a p38α mitogen-activated protein kinase (MAPK) mechanism. They may therefore be a target for amyloidosis therapy. By understanding how LCs cause cardiac dysfunction, we can target this process with therapies and utilize downstream measures of LC activity as diagnostic and prognostic tools. The objective of this study was to determine the role of autophagy in AL amyloidosis. Autophagy is the intracellular process of degrading aging or dysfunctional cellular components. Autophagy can be beneficial by preventing proteotoxicity and providing nutrients, amino acids, and other necessities during times of cellular stress. On the other hand, increased autophagy, like apoptosis, may mediate cellular death depending on the type of stimulus and its duration. Autophagy is induced by a variety of stimuli, including oxidative stress. AL has been demonstrated to increase reactive oxygen species (ROS), and it is unknown if autophagy mediates cardiomyocyte dysfunction in AL cardiac amyloidosis. We thus sought to determine if it is a factor in amyloid cardiotoxicity. We explored the ERK1/2, p38, and JNK MAPK pathways in particular, since MAPK signaling cascades regulate several transcription factors involved in the cell cycle and p38α has been implicated in ROS-induced cardiac AL amyloidosis. Adult rat ventricular myocytes (ARVM) were harvested from healthy adult male rats and exposed to a variety of experimental conditions in vitro. ARVM were treated with vehicle control, human LC obtained from a patient without cardiac involvement, a positive control (aldosterone), and human AL light chains obtained from a patient with AL cardiac amyloidosis in the presence or absence of UO126, SB203580, or SP600125 (specific inhibitors of ERK1/2, p38, and JNK, respectively). The resulting protein expression levels of autophagy indicators LC3II and ATG4B in cardiomyocytes were analyzed by Western blotting. The ratio of phosphorylated to total ERK1/2 protein expression was also explored. We found that AL light chains did not contribute to autophagy via the ERK1/2, p38, or JNK pathways. In contrast to our previous unpublished findings, the protein levels of autophagy indicators in AL-treated ARVM did not differ from vehicle control levels, suggesting that AL did not activate autophagy. However non-cardiomyopathic light chains (LC) did increase LC3II expression in ARVM, despite their human source exhibiting no clinical indications of cardiac involvement. This implies that autophagy induced by non-cardiomyopathic LCs may be beneficial and protect against the development of the cardiotoxicity seen in AL cardiac amyloidosis. Further studies are necessary to understand the effect of autophagy in the heart and its role in cardiac amyloidosis. Continuing to explore the underlying mechanisms of AL light chain toxicity will contribute to the development of diagnostic, prognostic, and treatment strategies for AL amyloidosis.

The cardiac ryanodine receptor (RyR2) plays a key role in excitation-contraction coupling (ECC). Mutations in RyR2 are known to be linked to the arrhythmogenic disorder, catecholaminergic polymorphic ventricular tachycardia (CPVT), a deadly disease which is characterized by a leak of calcium from sarcoplasmic reticulum and a decrease in calmodulin (CaM) binding. A novel drug, 84F2, shown to inhibit arrhythmias in RyR2-R176Q heterozygous CPVT mouse hearts (2.5 µg/kg), decrease spark frequency in cells derived from CPVT mice (IC50 = 35 nM), and inhibit RyR2 single channel activity at low nanomolar concentrations (IC50 = 8 nM). When CaM is added back to RyR2, 84F2's ability to inhibit channel activity is suppressed approximately 250 fold. A metabolite of 84F2, 78F3, is shown to also be active in the inhibition of RyR2. We propose that 84F2 decreases arrhythmias by binding to the CaM deficient RyR2, but does not affect normal ECC when CaM is present. This work characterizes for the first time a class of drugs whose inhibitory affects are dependent upon the removal of CaM from RyR2.

Abstract not available

<p>Background: Patients with heart failure is a patient group growing in numbers, the most common treatment focuses on reliving symptoms and the only cure is heart transplantation. <strong>Objective:</strong> Aim of the study was to illuminate patients' experiences of living with heart failure at his home. <strong>Method:</strong> Qualitative design, with a manifest content analysis. The results are based on 12 scientific articles.  <strong>Results:</strong> Patients with heart failure find that the disease is limited to their daily lives through mental illness and physical symptoms. The short comings of given information to the Patients are a necessary element to include in the planning for Patients future life. The Patients are experiencing that their lives are hanging on a thread as their life is running out, giving anxiety and worries. The need for palliative care is great, but is experienced by patients as containing large gaps. <strong>Discussion:</strong> Heart failure is a hidden disease, where patients with heart failure often feel like a burden on the environment. Dependence on other people gives a feeling of hope and hopelessness. <strong>Conclusion:</strong> information plays a large role in how patients with heart failure are able to live with their everyday lives.</p>

Remote ischemic preconditioning (rIPC) through transient limb ischemia induces potent cardioprotection against ischemia reperfusion (IR) injury. I examined the delayed phase of protection that appears 24 hours after the initial rIPC stimulus. The primary objective of this study was to establish a mode of sedation and control treatment for delayed rIPC experiments. I used an ex-vivo, Langendorff isolated-mouse heart preparation of IR injury to examine the delayed effects of an intra-peritoneal (IP) injection, sodium-pentobarbital (SP), halothane and nitrous oxide (N2O) anesthesia on post-ischemic cardiac function. Each anesthetic method improved left-ventricular function after IR injury. SP and halothane anesthesia also reduced LV infarct size. Delayed cardioprotection after IP injections was associated with an increase in phosphorylated-Akt levels. The present study shows that IP injections and inhalational anesthesia invoke cardioprotection and, therefore, indicates that these modes of sedation should not be used as control treatments for studies examining the delayed rIPC phenotype.

Remote ischemic preconditioning (rIPC) through transient limb ischemia induces potent cardioprotection against ischemia reperfusion (IR) injury. I examined the delayed phase of protection that appears 24 hours after the initial rIPC stimulus. The primary objective of this study was to establish a mode of sedation and control treatment for delayed rIPC experiments. I used an ex-vivo, Langendorff isolated-mouse heart preparation of IR injury to examine the delayed effects of an intra-peritoneal (IP) injection, sodium-pentobarbital (SP), halothane and nitrous oxide (N2O) anesthesia on post-ischemic cardiac function. Each anesthetic method improved left-ventricular function after IR injury. SP and halothane anesthesia also reduced LV infarct size. Delayed cardioprotection after IP injections was associated with an increase in phosphorylated-Akt levels. The present study shows that IP injections and inhalational anesthesia invoke cardioprotection and, therefore, indicates that these modes of sedation should not be used as control treatments for studies examining the delayed rIPC phenotype.

Εισαγωγή: Οι υπερκοιλιακές ταχυκαρδίες (ΥΤ) αποτελούν σημαντική αιτία νοσηρότητας στα παιδιά. Λόγω της χρονιότητας των συμπτωμάτων, η αντιαρρυθμική φαρμακευτική αγωγή δεν είναι ιδεώδης λύση. Η κατάλυση με ρεύμα ραδιοσυχνότητας (ΡΡ) μπορεί να προσφέρει ριζική θεραπεία. Στόχος: Η μελέτη αυτή είχε ως στόχο την ανάλυση των αποτελεσμάτων κατάλυσης υπερκοιλιακής ταχυκαρδίας (ΥΤ) στα παιδιά με ρεύμα ραδιοσυχνότητας (ΡΡ). Μεθοδολογία: Εξετάσαμε αναδρομικά τα στοιχεία 140 παιδιών ηλικίας 4-18 (12,8±3,5) ετών με ΥΤ που υπεβλήθησαν σε πλήρη ηλεκτροφυσιολογικό έλεγχο και κατάλυση με ΡΡ, είτε υπό γενική αναισθησία (84), είτε υπό καταστολή (56). Αποτελέσματα: Η τελική επιτυχία της κατάλυσης με ΡΡ μετά από τυχόν υποτροπές, ήταν 90/94 (95,7%) για ασθενείς (Α) με παραπληρωματικά δεμάτια (ΠΔ), 36/37 (97,3%) για Α με κομβική ταχυκαρδία επανεισόδου (ΚΤΕ), 10/10 για Α με έκτοπη κολπική ταχυκαρδία (ΕΚΤ), 3/3 για Α με κολπική ταχυκαρδία επανεισόδου και 1/1 για Α έκτοπη κομβική ταχυκαρδία. Σε Α με πρόσθια/διάμεσα διαφραγματικά ΠΔ παρατηρήθηκε υψηλότερος χρόνος ακτινοσκόπησης (p=0,05) και χαμηλότερη τελική επιτυχία (p=0,02). Οι υπόλοιπες κατηγορίες είχαν παρόμοια μεταξύ τους αποτελέσματα. Τα δεξιά πλάγια ΠΔ είχαν υψηλότερο ποσοστό συγγενών καρδιοπαθειών (p<0,001). Οι υποτροπές ήταν συχνότερες σε Α με πολλαπλά ΠΔ (p=0,007). Το ποσοστό μόνιμων σοβαρών επιπλοκών ήταν 1,4% (1 Α με ανεπάρκεια αορτής μετά από κατάλυση αριστερού ΠΔ με διαορτική τεχνική και 1 Α με πλήρη κολποκοιλιακό αποκλεισμό μετά από κατάλυση ΚΤΕ). Η τελική επιτυχία της επέμβασης, και τα ποσοστά υποτροπών και επιπλοκών ήταν ανεξάρτητα της ηλικίας. Συμπεράσματα: Η κατάλυση με ΡΡ μπορεί να αποτελέσει ριζική θεραπεία των ΥΤ στα παιδιά, χωρίς διαφορές στα αποτελέσματα σε ηλικίες >4 ετών. / Background: Supraventricular tachycardia (SVT) represents a significant cause of morbidity in children. Because of the chronic course, long-term treatment with antiarrythmic drugs is not an ideal solution. Radiofrequency ablation (RFA) may offer curative treatment. Purpose: The purpose of this study was to analyze the outcome of radiofrequency ablation (RFA) of supraventricular tachycardia (SVT) in children. Methodology: We reviewed retrospectively the charts of 140 patients (pts) 4-18 (12,8±3,5) years of age, who underwent complete electrophysiologic study and RFA., either under general anesthesia (84), or conscious sedation (56). Results: The final success of RFA, after possible recurrences, was 90/94 (95,7%) for pts with accessory pathways (AP), 36/37 (97,3%) for pts with AV nodal reentry tachycardia (AVNRT), 10/10 for pts with ectopic atrial tachycardia, 3/3 for pts with atrial reentry tachycardia, and 1/1 for a pt with junctional ectopic tachycardia. Longer fluoroscopy time (p=0,05) and lower final success (p=0,02) was observed in pts with anterior/mid-septal AP. The remaining categories had comparable results. Patients with right lateral AP had a higher prevalence of congenital heart disease (p<0,001). Recurrences were more frequent in pts with multiple AP (p=0,007). The incidence of severe permanent complications was 1,4% (1 pt with aortic insufficiency after retrograde RFA of left lateral AP, and 1 pt with complete AV block after RFA of AVNRT). The final success, recurrence rates and complication rates were independent of age. Conclusions: Treatment of SVT in children with RFA may offer permanent cure, without differences in outcomes in pts older than 4 years of age.