INTRODUCTION: Cirrhosis is a significant cause of mortality and morbidity worldwide. Recent studies suggested that cirrhosis is associated with an increased risk of venous thromboembolism (VTE), which disproves the old belief that chronic liver disease coagulopathy is considered protective against VTE. We conducted a retrospective study which is to our knowledge the first of its kind to assess clinical characteristics and outcomes of decompensated cirrhosis (DC) patients admitted with acute pulmonary embolism (APE). METHODOLOGY: We used the National Inpatient Sample database for the years 2016-2019. All adults admitted to the hospitals with a primary diagnosis of APE were included. Patients less than 18 years old, missing race, gender, or age were excluded. Patients were divided into two groups, either having DC or not. A multivariate logistic regression model was built by using only variables associated with the outcome of interest on univariable regression analysis at P < 0.05. RESULTS: 142 million discharges were included in the NIS database between the years 2016 and 2019, of which 1,294,039 met the study inclusion criteria, 6,200 patients (0.5%) had DC. For adult patients admitted to the hospitals with APE, odds of inpatient all-cause mortality were higher in the DC group than in patients without DC; OR of 1.996 (95% CI, 1.691-2.356, P-value < 0.000). Also, vasopressor use, mechanical ventilation, and cardiac arrest were more likely to occur in the DC group, OR of 1.506 (95% CI, 1.254-1.809, P-value < 0.000), OR of 1.479 (95% CI, 1.026-2.132, P-value 0.036), OR of 1.362 (95% CI, 1.050-1.767, P-value 0.020), respectively. In addition, DC patients tend to have higher total hospital charges and longer hospital length of stay, coefficient of 14521 (95% CI, 6752-22289, P-value < 0.000), and a coefficient of 1.399 (95% CI, 0.848-1.950, P-value < 0.000), respectively. CONCLUSION: This study demonstrates that DC is a powerful predictor of worse hospital outcomes in patients admitted with APE. An imbalance between clotting factors and natural anticoagulants produced by the liver is believed to be the primary etiology of thrombosis in patients with DC. The burden of APE can be much more catastrophic in cirrhotic than in non-cirrhotic patients; therefore, those patients require closer monitoring and more aggressive treatment.

Syfte: Syftet med studien var att beskriva vilka symtom som påverkade den hälsorelaterade livskvaliteten hos svårt leversjuka patienter samt beskriva hur symtomen påverkade patientens hälsorelaterade livskvalitet. Metod: Vetenskapliga artiklar söktes i databaserna Cinahl, Ovid Medline, Pubmed och PsycINFO. 15 vetenskapliga artiklar godkändes efter kvalitetsgranskning och låg till grund för resultatet. Resultat: I litteraturstudien framkom att patienternas hälsorelaterade livskvalitet påverkades av trötthet, hjärnpåverkan orsakat av sviktande leverfunktion, vätskeansamling i kroppen, klåda, smärta, muskelkramper, symtom från mag-tarmkanalen, benskörhet samt torrhet i ögon och mun. Symtomen påverkade i olika grad den psykiska-, fysiska- och sociala hälsorelaterad livskvaliteten. Psykiskt upplevde patienterna bristande energi och motivation, försämrad sömn, koncentrationssvårigheter, försämrad självkänsla, osäkerhet, frustration, skuld, otillräcklighet, rädsla, oro, ångest, depression och självmordstankar. De fysiska följderna innebar utmattning, andnöd, ökad smärtupplevelse och begränsad förmåga till fysisk aktivitet. Besvären innebar problem att hantera relationer, gav begränsningar i det yrkesverksamma livet, inskränkning i sociala aktiviteter samt svårigheter att klara av det dagliga livet. Slutsatser: Många symtom påverkade den svårt leversjuka patientens hälsorelaterade livskvalitet. Symtomen gav patienten problem att klara av olika vardagssituationer. Den genomförda litteraturstudien ger sjuksköterskan kunskap för att kunna tolka och bedöma de symtom som patienten beskriver.

Bei Patienten mit akut dekompensierter Herzinsuffizienz beziehungsweise kardiogenem Schock ist die Kurz- und die Langzeitprognose stark reduziert. Ziel dieser prospektiv klinischen Studie war die Feststellung des Maximums des NTproBNP-Wertes in der Akutphase innerhalb der ersten zwölf Stunden nach Krankenhausaufnahme sowie die Untersuchung der NTproBNP-Spiegel als Prädiktor der 18-Monatsmortalität in dieser Patientengruppe. Es wurden insgesamt 148 Patienten in zwei Studienabschnitten eingeschlossen, wobei die Kurz- und Langzeitverläufe aller Patienten zu den Zeitpunkten 0, 12, 24 und 48 Stunden, 7 und 14 Tagen sowie 1, 3 und 18 Monaten untersucht wurden. Bei 32 Patienten wurden zusätzlich regelmäßige zweistündliche Untersuchungen der NTproBNP-Werte innerhalb der ersten zwölf Stunden (2, 4, 6, 8 und 10 Stunden nach Aufnahme) durchgeführt. Für Patienten mit akut dekompensierter Herzinsuffizienz bzw. kardiogenem Schock ohne akuten Myokardinfarkt fanden sich innerhalb der ersten zwölf Stunden keine siginifikant erhöhten NTproBNP-Plasmaspiegel im Vergleich zum Aufnahmewert, eine statistische Signifikanz bezüglich der 18-Monatsmortalität fand sich in dieser Gruppe innerhalb der ersten 48 Stunden nur zum Zeitpunkt 12 Stunden nach Aufnahme. In der Gruppe der Patienten mit dekompensierter Herzinsuffizienz bzw. kardiogenem Schock im Rahmen eines akuten Myokardinfarktes dagegen fanden sich statistisch signifikant steigende NTproBNP-Werte zu allen Zeitpunkten innerhalb der ersten zwölf Stunden im Vergleich zum Aufnahmewert, wobei nach zwölf Stunden der Maximalwert erreicht wurde. Weiterhin zeigten in dieser Gruppe die NTproBNP-Werte eine statistische Signifikanz in Hinsicht auf die 18-Monatsmortalität zu fast allen Zeitpunkten außer 4 Stunden nach Aufnahme. Zusammenfassend kann somit mit Bestimmung der NTproBNP-Werte 12 Stunden nach Krankenhausaufnahme unabhängig von der Genese der akuten kardialen Dekompensation eine Kurz- und Langzeitprognoseabschätzung erfolgen.

Background and Aim: Bacterial infections are a well described complication of cirrhosis and occur in 37% of hospitalized patients. Culture positive infections in addition to the presence of bacterial products and DNA lead to loss of liver function and decompensation in cirrhosis. The mechanisms and molecular pathways associated with Bacterial Translocation (BT) are unknown. The aims of this study were to determine: i. macrophage phenotype and molecular pathways associated with bacterial translocation ii. if intestinal macrophages in liver cirrhosis are capable of modulating intestinal permeability.iii. structural integrity of the epithelial barrier. Methods: Duodenal biopsies and serum samples were collected from 29 patients with decompensated cirrhosis, 15 patients with compensated and 19 controls. Duodenal macrophages were characterized by means of flow cytometry and IHC. Gene expression analysis was performed to determine molecular pathways involved in BT. Inflammatory cytokine determination was done in serum and culture supernatant by means of customized cytometric bead arrays. Results: Patients with decompensated cirrhosis demonstrated: increased frequency of CD33+/CD14+/TREM-1+ and iNOS+ macrophages in their duodenum, elevated mRNA levels of nitric oxide synthase 2 (NOS2), chemokine ligand 2 (CCL2), chemokine ligand 13 (CCL13) and interleukin 8 (IL8) and increased serum levels of interleukin 6 (IL6), IL8 and lipopolysaccharides (LPS). Additionally, patients with decompensated cirrhosis showed an increase in NO, IL6, IL8 and CCL2 levels in culture supernatant after short term duodenal biopsy culture. Although the epithelial barrier on EM seemed intact, significantly increased expression of the “pore” forming tight junction claudin 2 was observed. Conclusion: This study showed the presence of activated CD14+Trem- 1+iNOS+ intestinal macrophages and increased levels of NO, IL-6 and claudin-2 levels in the duodenum of patients with decompensated liver cirrhosis, suggesting that these factors enhance intestinal permeability to bacterial products. / Afrikaans: Inleiding: Bakteriele infeksie is ‘n beskryfde komplikasie van lewersirrose wat in 37% van gehospitaliseerde pasiente voorkom. Kultuur positiewe infeksies asook die teenwoordigheid van bakteriele produkte en DNA lei tot verlies van lewerfunksie en dekompensasie. Die molekulere meganismes wat verband hou met bakteriele translokasie is nog onbekend. Die doel van hierdie studie was om: i. Makrofaag fenotipe en molekulere meganismes geassosieerd met bakteriele translokasie te beskryf, ii. te bepaal of intestinale makrofage dermdeurlaatbaarheid beinvloed, asook iii. om die struktruele integriteit van die dermwand te bepaal. Methods: Serum en dunderm biopsies was verkry van 29 pasiente met gedekompenseerde lewer sirrose, 15 pasiente met gekompenseerde sirrose en 19 kontroles. Dunderm makrofage was gekarakteriseer met behulp van vloeisitometrie en immunohistochemie. Molekulere meganisms belangrik tydens bakteriele translokasie was bepaal met behulp van geneekspressie. Serum en selkultuur supernatant sitokien bepalings was met Bioplex assays gedoen. Resultate: Pasiente met gedekompenseerde sirrose demonstreer: ‘n verhoogde frekwensie van CD33+/CD14+/TREM-1+ en iNOS+ makrofage in hul dunderm, verhoogde mRNA vlakke van NOS2, CCL2, CCL13 en IL8 asook verhoogde serum vlakke van IL6, IL8, LPS. Addisioneel het pasiente met gedekompenseerde sirrose vehoogde supernatant vlakke van NO, IL6, IL8 and CCL2 na kort termyn dunderm biopsie kulture. Alhoewel elekronmikroskopie gewys het dat die dundermwand intak is, was daar statisties-beduidend verhoogde ekspressie van die “porie” vormende vasteaansluitings- proteien, claudin 2 sigbaar. Gevolgtrekking: Gesamentlik het die studie gewys dat geaktiveerde CD14+/Trem-1+/iNOS+ intestinale makrofage asook verhoogde vlakke van NO, IL-6 en claudin-2 teenwoordig is in die dunderm van pasiente met gedekompenseerde sirrose. Dit dui daarop dat diè faktore derm deurlaatbaarheid vir bakteriele produkte kan verhoog. / Dissertation (MSc)--University of Pretoria, 2011. / Immunology / MSc / Unrestricted

Syfte: Att testa den patientenkät som används i utvärdering av en leversjuksköterskemottagning på patienter med dekompenserad levercirros för att undersöka upplevelsen av att besvara frågorna samt frågornas relevans till patientens situation. Metod: Pilotstudiens metod var mixad. Resultat: Spridningen av deltagarnas upplevelse av oro/obehag av enkäten var stor (VAS 6-100 millimeter). Vid få sjukdomssymtom väcktes oro om framtida sjukdomsutveckling men vid längre tids sjukdom kändes samtliga symtom igen, tankar om tidigare beteende uppstod vid alkoholsorsakad sjukdom. En mindre spridning (VAS 66-92 millimeter) sågs gällande hur viktiga/väsentliga frågorna upplevdes. Frågor om bemötande ansågs viktiga och påverkade upplevelsen av rätten till vård. Kompletterande frågor om individuellt anpassad information samt upplevelsen av delaktighet vid information efterfrågades. Deltagarna visade hög uppskattning (VAS 73-95 millimeter) till att sjukdomen/situation uppmärksammades genom enkäten. Besöken till sjuksköterskan skiljde sig från läkarbesök. Sjuksköterskan fokuserade på egenvård och mer tid fanns för information. För en informant innebar försöksverksamheten ökade antal sjukhusbesök, samordning innebar för- och nackdelar. Vid symtom på fatigue och nedsatt koncentrationsförmåga upplevdes enkäten lång, tvådelad enkät efterfrågades. Vid lindrig sjukdom upplevdes enkäten inte ansträngande. Språket var enkelt att förstå och innehållet upplevdes relevant. De öppna frågeställningarna tillförde inte något för de tre informanterna. / Purpose: To test the patient questionnaire used in the evaluation of an intervention with nurse-led clinic for patients with decompensated liver cirrhosis to examine the experience of answering the questions as well as their relevance to the patient's situation. Method: The pilot study was conducted with a mixed method. Results: The variation of the participants' experience of anxiety/discomfort of the questionnaire was large (VAS 6-100 millimeters). Individuals with few disease symptoms had concerns about future development of the disease, in the case of long disease experience all the symptoms was familiar. Following alcohol induced disease thoughts of past behavior occurred. A smaller variation (VAS 66-92 millimeters) was seen regarding the experience of how important/essential the questions felt. Questions about treatment were considered important and affected the perception of care. Questions about individualized information was requested as well as the experience of participation in the exchange of information. The participants showed a high appreciation (VAS 73-95 millimeters) that the disease/situation was highlighted by the survey. The visits to the nurse differed from appointments to physicians. The nurse focused on self-care and more time was available for information. For one informant the intervention increased the total number of hospital visits, coordination meant advantages and disadvantages. Symptoms of fatigue and impaired concentration made the questionnaire experienced as too long, a two-parted questionnaire was requested, the size was not strain in mild disease. The language was easy to understand and the content perceived relevant. The open issues brought nothing for the three informants.

Introduction: Chronic kidney disease (CKD) and congestive heart failure (CHF) patients have higher serum B-type natriuretic peptide (BNP), which alters the test interpretation. We aim to define BNP cutoff levels to diagnose acute decompensated heart failure (ADHF) in CKD according to CHF subtype: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Material and methods: We reviewed 1,437 charts of consecutive patients who were admitted for dyspnea. We excluded patients with normal kidney function, without measured BNP, echocardiography, or history of CHF. BNP cutoff values to diagnose ADHF for CKD stages according to CHF subtype were obtained for the highest pair of sensitivity (Sn) and specificity (Sp). We calculated positive and negative likelihood ratios (LR+ and LR–, respectively), and diagnostic odds ratios (DOR), as well as the area under the receiver operating characteristic curves (AUC) for BNP. Results: We evaluated a cohort of 348 consecutive patients: 152 had ADHF, and 196 had stable CHF. In those with HFpEF with CKD stages 3–4, BNP < 155 pg/ml rules out ADHF (Sn90%, LR– = 0.26 and DOR = 5.75), and BNP > 670 pg/ml rules in ADHF (Sp90%, LR+ = 4 and DOR = 6), with an AUC = 0.79 (95% CI: 0.71–0.87). In contrast, in those with HFrEF with CKD stages 3–4, BNP < 412.5 pg/ml rules out ADHF (Sn90%, LR– = 0.19 and DOR = 9.37), and BNP > 1166.5 pg/ml rules in ADHF (Sp87%, LR+ = 3.9 and DOR = 6.97) with an AUC = 0.78 (95% CI: 0.69–0.86). All LRs and DOR were statistically significant. Conclusions: BNP cutoff values for the diagnosis of ADHF in HFrEF were higher than those in HFpEF across CKD stages 3–4, with moderate discriminatory diagnostic ability. / Revisión por pares

Made available in DSpace on 2015-07-22T20:50:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-11-25. Added 1 bitstream(s) on 2015-08-11T03:25:54Z : No. of bitstreams: 1 Publico-11760a.pdf: 1069601 bytes, checksum: 88c7a2d10e394e1888e3b93a69070de4 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:54Z : No. of bitstreams: 2 Publico-11760a.pdf: 1069601 bytes, checksum: 88c7a2d10e394e1888e3b93a69070de4 (MD5) Publico-11760b.pdf: 1959621 bytes, checksum: 2665d88fb8fec237d73fdc84aa78a26a (MD5) / Introdução: A insuficiência cardíaca congestiva (ICC) descompensada pode ser definida como a evidência de sinais e sintomas de insuficiência cardíaca (IC) ao repouso e representa estado de ativação neuro-hormonal intensa, secundária ao déficit de perfusão renal. Regurgitações valvares funcional mitral e tricúspide são causas reversíveis de diminuição de fluxo sanguíneo sistêmico eficaz. O impacto de tais regurgitações sobre o débito cardíaco, sobre o conteúdo de fluido torácico, sobre as dimensões de câmaras cardíacas e sobre a função do aparato valvular pode ser monitorado de forma não-invasiva, antes e após a otimização do tratamento clínico. Objetivo: Avaliar o papel das regurgitações valvares funcional mitral e tricúspide como causas reversíveis de redução do débito cardíaco em ICC descompensada, e que acompanham a disfunção ventricular sistólica em miocardiopatias isquêmica e não-isquêmica. Métodos: catorze pacientes do sexo masculino (66 ± 8 anos de idade), fração de ejeção (24 ± 5%) secundária às miocardiopatias isquêmica (71%) e não-isquêmica (29%), apresentaram ICC descompensada com evidência clínica de regurgitações valvares mitral e tricúspide, foram avaliados por Bioimpedância cardíaca e ecocardiografia antes e uma semana após otimização de tratamento clínico. Resultados: o tratamento farmacológico de ICC descompensada foi acompanhado de redução de peso corpóreo de 82,9 a 76 kg (P<0,01), elevação no índice cardíaco (de 2,1 para 2,6 L/min/m2; P<0,01), redução na pressão sistólica da artéria pulmonar (de 58 para 35 mm Hg; P<0,001), conteúdo de fluido torácico (de 39 para 32 kOhm; P<0,001) e resistência vascular sistêmica (de 1633 para 1209 dinas/seg/cm5; P<0.001). A melhora dessas regurgitações incluiu redução nas dimensões das câmaras atriais esquerda e direita (de 27 para 24 cm2 e de 26 para 23 cm2, respectivamente; (P<0,001), diminuição das regurgitações mitral e tricúspide detectadas pelo Doppler colorido (P < 0,01), do volume regurgitante mitral (de 105 para 65 ml; P<0,001), e do tamanho efetivo do orifício regurgitante mitral (de 0,8 para 0,6 cm2; P<0,01). Conclusões: Na ICC descompensada, as regurgitações funcionais mitral e tricúspide contribuem para redução do débito cardíaco, aumento do conteúdo fluido torácico e da resistência vascular sistêmica, simultaneamente ao aumento de câmaras atriais e do orifício valvar, os quais podem ser melhorados com tratamento clínico. A bioimpedância cardíaca e a ecocardiografia fornecem avaliação seriada não-invasiva de parâmetros hemodinâmicos e função valvar nestes pacientes. / Objective: We hypothesized that functional mitral and tricuspid valvular incompetence (MR and TR, respectively) are reversible causes of reduced cardiac output in decompensated heart failure (DF) that accompanies systolic dysfunction in ischemic or nonischemic cardiomyopathy. Background: DF, defined as signs and symptoms of heart failure at rest, is rooted in a salt-avid state transduced by neurohormonal activation secondary to impaired renal perfusion. Functional MR and TR are reversible causes of reduced systemic blood flow. Their impact on cardiac output, thoracic fluid content, cardiac chamber dimensions, and valvular apparatus function can be monitored noninvasively, before and after optimized medical management. Methods: Fourteen male subjects (66 ± 8 years old) with reduced ejection fraction (24 ± 5%) secondary to ischemic (71%) or nonischemic (29%) cardiomyopathy, who developed DF with clinical evidence of mitral (MR) and tricuspid (TR) valvular incompetence, were each assessed by bioimpedance and echocardiography before and 1 week after optimized medical management restored compensated failure. Results: Pharmacologic elimination of DF was accompanied by a reduction in body weight (p<0.01). Hemodynamic improvements included a rise in cardiac index (2.1 to 2.6 L/min/m2; p<0.01) and a reduction in predicted pulmonary artery systolic pressure (58 to 35 mm Hg; p<0.001), thoracic fluid content (39 to 32 kOhm; p<0.001), and systemic vascular resistance (1633 to 1209 dynes/sec/cm5; p<0.001). Improvements in functional MR and TR included reductions in left and right atrial areas (27 to 24 cm and 26 to 23 cm2, respectively; p<0.001), color-flow grading of MR and TR severity (p<0.01), mitral regurgitant volume (105 to 65 mL; p<0.001), and effective MR orifice size (0.8 to 0.6 cm2; p<0.01). Conclusions: In DF, functional MR and TR contribute to reduced cardiac output, increased thoracic fluid content, and systemic vascular resistance, together with enlarged atria and valvular orifice size, which can be improved by medical management. Bioimpedance and echocardiography provide for serial noninvasive assessments of hemodynamic status and valvular function in such cases. / TEDE / BV UNIFESP: Teses e dissertações

Akut hjärtsvikt definieras som en debut eller försämring av hjärtsvikt. Hjärtsvikt är ett allvarligt tillstånd där hjärtat inte upprätthåller adekvat hjärtminutvolym för att möta kroppens metaboliska behov vilket leder till trötthet och försämrad livskvalitet. Symtom som relaterar till systemisk vätskeansamling är vanliga vid akut hjärtsvikt. Vätskeansamling och hypoperfusion ökar morbiditet och mortalitet. Patienter med akut hjärtsvikt behöver således snabba och effektiva behandlingar, men också långtidsbehandling efter utskrivning. Avsvällande/vattendrivande behandling är hörnstenen i den terapeutiska behandlingen och loopdiuretika anses som det mest effektiva och snabbverkande läkemedlet. I dagsläget är empagliflozin ett rekommenderat läkemedel för behandling av kronisk hjärtsvikt med nedsatt ejektionsfraktion, då empagliflozins diuretiska egenskap kan stärka effekten av loopdiuretika.   Syftet med detta examensarbete var att beskriva effekter hos empagliflozin vid behandling av akut hjärtsvikt som en litteraturstudie. En sökning av randomiserade kliniska prövningar gjordes i PubMed där nio artiklar valdes ut för att ingå i detta examenarbete. Resultatet av de granskade artiklarna visade att empagliflozin som tilläggsbehandling till loopdiuretika ökade urinutsöndring hos patienterna. Resultatet visade också en statistiskt signifikant minskning av NT-proBNP i studierna vars behandlingstid var 5, 7, 15 och 30 dagar jämfört med placebo. Vidare minskade empagliflozin också plasmavolymen och mängden urinsyran i plasman. Två av studierna rapporterade en statistiskt signifikant ökning i andel röda blodkroppar i behandlingsgruppen. Insättning av empagliflozin, hos kliniskt stabila sjukhusvårdade patienterna i studien EMPULSE, gav en statistiskt signifikant klinisk nytta definierat som ett hierarkiskt kompositmått av död oavsett orsak, antal hjärtsviktsepisoder, tid till första hjärtsviktsepisod och klinisk meningsfull förbättring i KCCQ-TSS med vinstratio 1,36. Vidare gav empagliflozin en positiv effekt på viktminskning, ökad diuretisk respons, ödemlindring och ökad livskvalitet under 90 dagars behandling. Hos patienter som fick empagliflozin sänktes eGFR något till en början men återställdes senare. Det fanns dock inte någon statistiskt signifikant skillnad i eGFR mellan grupperna. En av studierna visade på en signifikant minskning av biomarkörer hos patienter som fick empagliflozin vilket gav en njurfunktionsskyddande effekt mot akut njurskada.  Slutsatsen var att empagliflozin gav gynnsamma effekter såsom till exempel avsvällande/vätskedrivande effekt och klinisk fördel hos patienter med såväl akut de novo som med dekompenserad kronisk hjärtsvikt vilket betydde att läkemedlet var både säkert och effektivt. I framtiden behöver effekterna dock styrkas genom ytterligare studier med större antal deltagare och under längre behandlingstid efter sjukhusutskrivning.

A sobrecarga crônica de pressão causa hipertrofia, disfunção e insuficiência cardíaca (IC). O mecanismo envolvido na transição da hipertrofia cardíaca compensada para descompensada ainda não é totalmente entendido. Evidências sugerem que modificações nas proteínas contráteis poderiam contribuir para disfunção contrátil e evolução para IC. Neste sentido, estudos mostraram mudanças na expressão das proteínas da maquinaria contrátil durante o desenvolvimento da doença cardíaca como um mecanismo inicialmente benéfico. Porém, na insuficiência cardíaca, ocorrem alterações estruturais que prejudicam a contratilidade. Contudo, não se sabe ao certo quais proteínas estariam contribuindo para a transição da hipertrofia compensada para a insuficiência cardíaca. Este estudo teve como objetivo investigar as alterações das proteínas da maquinaria contrátil na transição da hipertrofia cardíaca compensada para descompensada e correlacionar essas alterações com a função cardíaca. Ratos Wistar machos foram submetidos a estenose da aorta abdominal. Após 90d da cirurgia, foram realizados ecocardiograma, análise da pressão sanguínea e os corações foram coletados para realização do Western blot e imunofluorescência para miosina de cadeia pesada, actina sarcomérica, troponina T e troponina I. Os dados foram considerados significantes quando p<0,05. Aos 90d, 70,0±5,35% dos animais apresentaram hipertrofia cardíaca (HH) e 30,3±4,79% corações hipertrofiados+dilatados (HD). A pressão arterial média aumentou 58,2% no HH e 55,0% no HD. As? expressões? de? ?-actina sarcomérica, miosina de cadeia pesada, troponina T e I aumentaram no grupo HH. No grupo HD, a miosina de cadeia pesada e a troponina T reduziram significantemente. A função sistólica manteve-se preservada nos grupos controle e HH, porém reduzida no HD. A perda estrutural da miosina de cadeia pesada e da troponina T poderia contribuir para a insuficiência cardíaca observada nesse modelo experimental. / Hypertension causes hypertrophy, cardiac dysfunction and heart failure (HF). The mechanisms implicated in the transition from compensated to decompensated cardiac hypertrophy are not fully understood. There is considerable evidence that changes in the contractile proteins may contribute to the contractile dysfunction and progression to HF. Studies have shown changes in the expression of contractile proteins during the development of heart disease as a mechanism that is initially beneficial. However, in heart failure there is an intrinsic reduction of cross-bridges that contributes to impaired contractility. It is not known which proteins are contributing to the transition from compensated hypertrophy to heart failure. We investigated ?-sarcomeric actin, heavy chain myosin and troponins T and I in the transition from compensated to decompensated cardiac hypertrophy and correlate these alterations with cardiac function. Male Wistar rats were submitted to abdominal aorta constriction and killed at 90 days post-surgery (dps). The hearts were collected; Western blot and immunofluorescence were performed to investigate ?-sarcomeric actin, heavy chain myosin and troponins T and I. Blood pressure and cardiac systolic function were evaluated. Data were considered significant when p<0.05. At 90 dps, 70,0±5,35% presented hypertrophic hearts (HH) and 30,3±4,79% hypertrophic+dilated hearts (HD). Mean blood pressure increased 58.19% in HH and 54.96% in HD. Heavy chain myosin, troponin T, troponin I and ?-sarcomeric actin expression increased in HH. In HD, only heavy chain myosin and troponin T reduced significantly. The systolic function was the same in control and HH animals and reduced in HD. The structural loss of heavy chain myosin and troponin T could contribute to heart failure observed in this experimental model of abdominal aorta constriction.

Introdução. Frequência cardíaca (FC) elevada é reconhecida como um fator prognóstico de maior mortalidade na insuficiência cardíaca aguda descompensada (ICAD). Entretanto, pouco se conhece sobre os efeitos da redução da FC na evolução de pacientes com ICAD em ritmo sinusal, não havendo estudo clínico desenhado especificamente para o esclarecimento desta questão até o momento. Objetivos. Avaliar a eficácia e segurança da redução da FC através da inibição da corrente I(f) atrial em pacientes hospitalizados com ICAD em ritmo sinusal. Avaliar os efeitos de curto prazo da redução da FC nos parâmetros hemodinâmicos e de função ventricular por ecocardiografia e sobre os biomarcadores séricos de IC. Métodos. Estudo clínico randomizado, duplo-cego, controlado com placebo, unicêntrico. Os critérios de inclusão foram admissão por ICAD, fração de ejeção do ventrículo esquerdo (FEVE) < 40%, FC >80 bpm, INTERMACS >= 3 e ritmo sinusal. Os participantes do estudo (n=46, 48% feminino, idade média de 48±15 anos) receberam tratamento da ICAD orientado por diretriz e 5 mg de ivabradina (N = 23) ou placebo (N = 23) de 12/12 horas por 1 mês. Os desfechos estudados foram a variação em relação ao basal, aferida no quinto dia de intervenção, das seguintes variáveis: FC, pressão arterial sistêmica; volume sistólico (VS), índice cardíaco (Icar), FEVE, strain longitudinal global do VE (SLG-VE), índice de performance do miocárdio (IPM), relação E/A, tempo de desaceleração da onda E (TD onda E), relação E/e´, excursão sistólica máxima do anel tricúspide lateral (TAPSE), velocidade sistólica máxima do anel tricúspide lateral (s´), variação fracional da área do ventrículo direito (VFA), strain longitudinal global do ventrículo direito (SLG-VD), peptídeo natriurético tipo B (BNP), troponina, proteína C reativa (PCR), creatinina e NGAL (neutrophil gelatinase-associated lipocalin). Os pacientes foram acompanhados durante a internação e após a alta até o sexto mês, ou até a ocorrência de um evento cardiovascular pré-especificado. Resultados. A ivabradina reduziu significativamente a FC em comparação com o placebo (-14 ± 5 vs 0,2 ± 6 bpm, p < 0,001). A redução da FC acompanhou-se de melhora na FEVE (5,5 ± 15 vs -3,0 ± 11%, p = 0,03), no VS do VE (5,8 ± 11 vs -1,8 ± 10 mL, p = 0,02), no SLG-VD (2,0± 2,2 versus 0,3 ± 3,1%, p = 0,007), no TAPSE (1,6 ± 2,4 vs. -0,2 ± 1,7 mm, p = 0,004), na VFA (5,1 ± 7,8 vs -1,4 ± 4,5%, p = 0,001) e na s´ (0,5 ± 1,3 vs. -0.4 ± 1,0 cm/s, p = 0,009). Não houve diferença na pressão arterial sistêmica, Icar, IPM, TD onda E, BNP, troponina, PCR, NGAL e creatinina. Dos 46 pacientes, 24 (52%) apresentaram eventos adversos durante o acompanhamento, com 6 óbitos e 3 transplantes no grupo placebo e 5 óbitos e 2 transplantes no grupo tratado com ivabradina. A FC no quinto dia da intervenção foi um forte preditor de eventos de acordo com o modelo de risco proporcional de Cox (HR 1,08 [IC95% 1,03-1,12], p < 0.001), mesmo quando corrigida pela idade, tempo de diagnóstico de IC e gênero. Conclusão. Os dados sugerem que a inibição da I(f) reduz de forma segura a FC em pacientes admitidos por ICAD em ritmo sinusal, com benefício para a função cardíaca global. Nosso estudo sugere que a FC elevada pode ser considerada um potencial alvo terapêutico em pacientes com ICAD em ritmo sinusal, sendo necessário um estudo multicêntrico sobre o tema / Introduction. Elevated heart rate (HR) is a known prognostic factor of higher mortality in acute decompensated heart failure (ADHF). However, little is known about the effects of HR reduction on the progression of patients with ADHF in sinus rhythm, and there was no clinical study specifically designed to clarify this issue to date. Aims. To evaluate the efficacy and safety of HR reduction through inhibition of the atrial I(f) current in patients hospitalized with ADHF in sinus rhythm. To evaluate the short-term effects of HR reduction on hemodynamic and ventricular function parameters by echocardiography and on serum biomarkers of HF. Methods. Randomized, double-blind, placebo-controlled, single-center clinical trial. Inclusion criteria were ADHF, left ventricle ejection fraction (LVEF) <40%, HR >80 bpm, INTERMACS >= 3 and sinus rhythm. Participants in the study (n = 46, 48% female, mean age 48 ± 15 years) received guideline-guided treatment for ADHF and 5 mg ivabradine (N = 23) or placebo (N = 23) 12/12 hours for 1 month. Outcomes were change from baseline measured on the fifth day of intervention for the following variables: HR, systemic arterial pressure, LV stroke volume (LVSV), cardiac index (CI), LVEF, LV global longitudinal strain (LV-GLS), myocardial performance index (MPI), E/A, E wave deceleration time (E wave DT), E/e\' ratio, tricuspid annular plane systolic excursion (TAPSE), tricuspid annular plane peak-systolic velocity (s´), right ventricle (RV) fractional area change (FAC), RV global longitudinal strain (RV-GLS), B-type natriuretic peptide (BNP), troponin, reactive C protein (RCP), creatinine, and neutrophil gelatinase-associated lipocalin (NGAL). Patients were followed up during hospitalization and after discharge until the sixth month, or until the occurrence of a pre-specified cardiovascular event. Results. Ivabradine significantly reduced HR compared with placebo (-14 ± 5 vs 0.2 ± 6 bpm, p < 0.001). The HR reduction was accompanied by improvement in LVEF (5.5 ± 15 vs -3.0 ± 11%, p = 0.03), LVSV (5.8 ± 11 vs -1.8 ± 10 mL, p = 0.02), RV-GLS (2.0 ± 2.2 versus 0.3 ± 3.1%, p = 0.007), TAPSE (1.6 ± 2.4 vs. -0.2 ± 1,7 mm, p = 0.004), FAC (5.1 ± 7.8 vs -1.4 ± 4.5%, p = 0.001) and s´ (0.5 ± 1.3 vs. -0.4 ± 1.0 cm / s, p = 0.009). There was no difference in systemic arterial pressure, CI, MPI, E wave TD, BNP, troponin, RCP, NGAL and creatinine. Of the 46 patients, 24 (52%) presented events during follow-up, with 6 deaths and 3 transplants in placebo group and 5 deaths and 2 transplants in ivabradine group. HR on the fifth day of the intervention was a strong event predictor according to Cox proportional hazards model (HR 1.08 [95% CI 1.03-1.12], even when corrected for age, time from diagnosis of HF and gender. Conclusion. The data suggest that I(f) inhibition safely reduces HR in patients admitted with ADHF in sinus rhythm, with benefit to global cardiac function. Our study suggests that elevated HR may be considered a potential therapeutic target in patients with ADHF in sinus rhythm, requiring a multicenter study on the subject