Complications associated with the use of temporary pacemaker in patients waiting for definitive device implantation.

OBJECTIVE: To determine the rate of complications associated with the use of temporary pacemakers in patients in the waiting list for the definitive pacemaker implantation in a public hospital located in São Paulo, SP, Brazil. METHODS: Retrospective observational study based on data extracted from medical records of patients admitted to Hospital Municipal Dr. Moyses Deutsch, Hospital Israelita Albert Einstein from January 2014 to December 2018. Patients aged 18 years or older, diagnosed with high degree atrioventricular block upon admission and with indications for definitive pacemaker implantation were included. All-cause mortality, clinical and surgical complications and length of hospital stay while waiting for the procedure were defined as primary outcomes. RESULTS: The sample comprised 66 patient allocated to one of two groups: with and without the need of temporary pacemaker while in hospital (n=45 and n=21, respectively). The rate of complications was higher in patients who used a temporary pacemaker (p<0.001). These included primarily pneumonia (p=0.048) and length of hospital stay (p=0.029). CONCLUSION: Patients who required a temporary pacemaker stayed longer in hospital. Longer hospital stay is associated with higher rates of general complications and all-cause mortality.

Complications associated with the use of temporary pacemaker in patients waiting for definitive device implantation

ABSTRACT Objective To determine the rate of complications associated with the use of temporary pacemakers in patients in the waiting list for the definitive pacemaker implantation in a public hospital located in São Paulo, SP, Brazil. Methods Retrospective observational study based on data extracted from medical records of patients admitted to Hospital Municipal Dr. Moyses Deutsch, Hospital Israelita Albert Einstein from January 2014 to December 2018. Patients aged 18 years or older, diagnosed with high degree atrioventricular block upon admission and with indications for definitive pacemaker implantation were included. All-cause mortality, clinical and surgical complications and length of hospital stay while waiting for the procedure were defined as primary outcomes. Results The sample comprised 66 patient allocated to one of two groups: with and without the need of temporary pacemaker while in hospital (n=45 and n=21, respectively). The rate of complications was higher in patients who used a temporary pacemaker (p<0.001). These included primarily pneumonia (p=0.048) and length of hospital stay (p=0.029). Conclusion Patients who required a temporary pacemaker stayed longer in hospital. Longer hospital stay is associated with higher rates of general complications and all-cause mortality.

Exhaled breath acetone for predicting cardiac and overall mortality in chronic heart failure patients.

AIMS: Exhaled breath acetone (EBA) has been described as a new biomarker of heart failure (HF) diagnosis. EBA concentration increases according to severity of HF and is associated with poor prognosis, especially in acute decompensated HF. However, there are no data on chronic HF patients. The aim is to evaluate the role of EBA for predicting cardiac and overall mortality in chronic HF patients. METHODS AND RESULTS: In GENIUS-HF cohort, chronic patients were enrolled between August 2012 and December 2014. All patients had left ventricular ejection fraction ≤ 50%, and the diagnosis was established according to Framingham criteria. After consent, patients were submitted to clinical evaluation and exhaled breath collection. EBA identification and quantitative determination were done by spectrophotometry. The clinical characteristics associated with acetone were identified. All participants were followed for 18 months to assess cardiac and overall mortality. Around 700 participants were enrolled in the current analysis. Patients were 55.4 ± 12.2 years old, 67.6% male patients, and 81% New York Heart Association I/II with left ventricular ejection fraction of 32 ± 8.6%. EBA median concentration was 0.6 (0.3-1.2) ug/L. Acetone levels increased with the number of symptoms of HF and were associated with right HF signs/symptoms and liver biochemical changes. EBA at highest quartile (EBA > 1.2ug/L) was associated with a significantly worse prognosis (log rank test, P < 0.001). Cox proportional multivariable regression model revealed that EBA > 1.20ug/L was an independent predictor of cardiac (P = 0.011) and overall (P = 0.010) mortality in our population. CONCLUSIONS: This study shows that EBA levels reflect clinical HF features, especially right HF signs/symptoms. EBA is an independent predictor of cardiac and overall mortality in chronic HF patients.

Predictors of one-year outcomes in chronic heart failure: the portrait of a middle income country.

BACKGROUND: Heart failure (HF) is a major public health problem with increasing prevalence worldwide. It is associated with high mortality and poor quality of life due to recurrent and costly hospital admissions. Several studies have been conducted to describe HF risk predictors in different races, countries and health systems. Nonetheless, understanding population-specific determinants of HF outcomes remains a great challenge. We aim to evaluate predictors of 1-year survival of individuals with systolic heart failure from the GENIUS-HF cohort. METHODS: We enrolled 700 consecutive patients with systolic heart failure from the SPA outpatient clinic of the Heart Institute, a tertiary health-center in Sao Paulo, Brazil. Inclusion criteria were age between 18 and 80 years old with heart failure diagnosis of different etiologies and left ventricular ejection fraction ≤50% in the previous 2 years of enrollment on the cohort. We recorded baseline demographic and clinical characteristics and followed-up patients at 6 months intervals by telephone interview. Study data were collected and data quality assurance by the Research Electronic Data Capture tools. Time to death was studied using Cox proportional hazards models adjusted for demographic, clinical and socioeconomic variables and medication use. RESULTS: We screened 2314 consecutive patients for eligibility and enrolled 700 participants. The overall mortality was 6.8% (47 patients); the composite outcome of death and hospitalization was 17.7% (123 patients) and 1% (7 patients) have been submitted to heart transplantation after one year of enrollment. After multivariate adjustment, baseline values of blood urea nitrogen (HR 1.017; CI 95% 1.008-1.027; p < 0.001), brain natriuretic peptide (HR 1.695; CI 95% 1.347-2.134; p < 0.001) and systolic blood pressure (HR 0.982;CI 95% 0.969-0.995; p = 0.008) were independently associated with death within 1 year. Kaplan Meier curves showed that ischemic patients have worse survival free of death and hospitalization compared to other etiologies. CONCLUSIONS: High levels of BUN and BNP and low systolic blood pressure were independent predictors of one-year overall mortality in our sample. TRIAL REGISTRATION: Current Controlled Trials NTC02043431, retrospectively registered at in January 23, 2014.

Temporal trends in the contribution of Chagas cardiomyopathy to mortality among patients with heart failure.

BACKGROUND: Chagas cardiomyopathy (ChC) prevalence is decreasing in Brazil and medical therapies for heart failure (HF) have improved in the last decade. Whether these changes modified the prognosis of ChC relative to non-Chagas cardiomyopathies (NChC) remains unknown. This study evaluated the temporal trends in population attributable risk (PAR) of ChC for 2-year mortality among patients with HF enrolled at years 2002-2004 (era 1) and 2012-2014 (era 2) in a Brazilian university hospital. METHODS: We prospectively studied 362 (15% with ChC) and 582 (18% with ChC) HF patients with ejection fraction ≤50% in eras 1 and 2, respectively and estimated the PAR of ChC for 2-year mortality. RESULTS: There were 145 deaths (29 in ChC) in era 1 and 85 deaths (26 in ChC) in era 2. In multivariable Cox-regression analysis adjusted for age, sex, ejection fraction, heart rate, body mass index, hypertension, diabetes mellitus, systolic blood pressure and ischaemic/valvar aetiology, ChC was associated with higher risk of death in era 1 (HR (95% CI)=1.92 (1.00 to 3.71), p=0.05) and era 2 (HR (95% CI)=3.51 (1.94 to 6.36), p<0.001). In fully adjusted analysis, the PAR of ChC for mortality increased twofold from era 1 (PAR (95% CI)=11.0 (2.8 to 18.5)%) to era 2 (PAR (95% CI)=21.9 (16.5 to 26.9)%; p=0.023 versus era 1). CONCLUSION: Although the absolute death rates decreased over time in the ChC and NChC groups, the PAR of ChC for mortality increased among patients with HF, driven by increases in the HR associated with ChC. Our results highlight the need for additional efforts aiming to prevent and treat ChC.

Genomic ancestry as a predictor of haemodynamic profile in heart failure.

OBJECTIVE: The aim of this study is to assess the association between genetic ancestry, self-declared race and haemodynamic parameters in patients with chronic heart failure (HF). METHODS: Observational, cross-sectional study. Eligible participants were aged between 18 and 80 years; ejection fraction was ≤50%. Patients underwent genetic analysis of ancestry informative markers, echocardiography and impedance cardiography (ICG). Race was determined by self-classification into two groups: white and non-white. Genomic ancestry was estimated using a panel of 101 348 polymorphic markers and three continental reference populations (European, African and Native American). RESULTS: Our study included 362 patients with HF between August 2012 and August 2014. 123 patients with HF declared themselves as white and 234 patients declared themselves as non-white. No statistically significant differences were found regarding the ICG parameters according to self-declared race. The Amerindian ancestry was positively correlated with systolic time ratio (r=0.109, p<0.05). The thoracic fluid content index (r=0.124. p<0.05), E wave peak (r=0.127. p<0.05) and E/e' ratio (r=0.197. p<0.01) were correlated positively with African ancestry. In multiple linear regression, African ancestry remained associated with the E/e' ratio, even after adjustment to risk factors. CONCLUSIONS: The African genetic ancestry was associated with worse parameters of diastolic function; the Amerindian ancestry correlated with a worse pattern of ventricular contractility, while self-declared colour was not helpful to infer haemodynamic profiles in HF. TRIALS REGISTRATION NUMBER: NTC02043431.

Genetic and ElectroNic medIcal records to predict oUtcomeS in Heart Failure patients (GENIUS-HF) - design and rationale.

BACKGROUND: Studies adopting electronic medical records and genomic information are becoming widespread. Through this new modality in research, it is possible to study how genetic variants influence susceptibility towards chronic conditions and can improve patient care.Our aim is to develop a biobank with 2,000 heart failure patients treated in a tertiary cardiology hospital containing electronic medical records data and biologic samples for performing genome-wide association studies for validation and development of medical decision routines aimed at helping the clinical management of patients. METHODS/DESIGN: Patients between 18 and 80 years old with heart failure diagnosis of different etiologies and left ventricular ejection fraction ≤ 50% in the past 2 years will be eligible for enrollment on the cohort. After consent, patients will be submitted to clinical baseline, echocardiography, cardiograph impedance and biochemical evaluation. Study data will be collected and managed using Research Electronic Data Capture tools. The follow up will take place every 6 months to assess cardiovascular outcomes (all-cause mortality, cardiovascular mortality, hospitalization for worsening heart failure and current medication use). Initial analytical strategy will focus on the establishment of the accuracy of electronic medical records extraction protocols for main predictor factors of morbidity and mortality in heart failure. DISCUSSION: Building a biobank with biologic samples and clinical data of 2,000 heart failure patients we will perform genome-wide association studies. By this way, we pretend to study how genetic variants influence susceptibility towards chronic conditions. Besides, it will be created a working group focused on the development and implementation of algorithms for validation and application of medical routines using the electronic medical records of the Heart Institute (InCor - HCFMUSP). TRIAL REGISTRATION: Current Controlled Trials NTC02043431.

Association between UCP2 A55V polymorphism and risk of cardiovascular events in patients with multi-vessel coronary arterial disease.

BACKGROUND: UCP2 (uncoupling protein 2) plays an important role in cardiovascular diseases and recent studies have suggested that the A55V polymorphism can cause UCP2 dysfunction. The main aim was to investigate the association of A55V polymorphism with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease and preserved left ventricular function. METHODS: The participants of the MASS II were genotyped for the A55V polymorphism using allele-specific PCR assay. Survival curves were calculated with the Kaplan-Meier method and evaluated with the log-rank statistic. The relationship between baseline variables and the composite end-point of cardiac death, acute myocardial infarction (AMI), refractory angina requiring revascularization and cerebrovascular accident were assessed using a Cox proportional hazards survival model. RESULTS: There were no significant differences for baseline variables according genotypes. After 2 years of follow-up, dysglycemic patients harboring the VV genotype had higher occurrence of AMI (p=0.026), Death+AMI (p=0.033), new revascularization intervention (p=0.009) and combined events (p=0.037) as compared with patients carrying other genotypes. This association was not evident in normoglycemic patients. CONCLUSIONS: These findings support the hypothesis that A55V polymorphism is associated with UCP2 functional alterations that increase the risk of cardiovascular events in patients with previous coronary artery disease and dysglycemia.

Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21.

BACKGROUND: We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. METHODS: The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model. RESULTS: We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p = 0.01; 52.4% and 40.1%, p = 0.01; 47.8% and 37.9%, p = 0.04; respectively). Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p = 0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p = 0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy. CONCLUSIONS: Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios. In patients with established CAD, we observed an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.

NKX2.5 mutations in patients with non-syndromic congenital heart disease.

BACKGROUND: Cardiac development is a complex and multifactorial biological process. Heterozygous mutations in the transcription factor NKX2.5 are between the first evidence of a genetic cause for congenital heart defects in human beings. In this study, we evaluated the presence and frequency of mutations in the NKX2.5 gene on 159 unrelated patients with a diverse range of non-syndromic congenital heart defects (conotruncal anomalies, septal defects, left-sided lesions, right-sided lesions, patent ductus arteriosus and Ebstein's anomaly). METHODS: The coding region of the NKX2.5 locus was amplified by polymerase chain reaction and mutational analysis was performed using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. RESULTS: We identified two distinct mutations in the NKX2.5 coding region among the 159 (1.26%) individuals evaluated. An Arg25Cys mutation was identified in a patient with Tetralogy of Fallot. The second mutation found was an Ala42Pro in a patient with Ebstein's anomaly. CONCLUSIONS: The association of NKX2.5 mutations is present in a small percentage of patients with non-syndromic congenital heart defects and may explain only a few cases of the disease. Screening strategies considering the identification of germ-line molecular defects in congenital heart disease are still unwarranted and should consider other genes besides NKX2.5.

Fate of bradykinin on the rat liver when administered by the venous or arterial route.

BACKGROUND AND AIM: Bradykinin (BK) infused into the portal vein elicits a hypertensive response via the B2 receptor (B2R) and is efficiently hydrolyzed by the liver. Our purpose was to characterize the mechanism of interaction between BK and the liver. METHOD: BK, HOE-140 (a B2R antagonist), des-R(9)-BK (a B1R agonist) and enzyme inhibitors were used in monovascular or bivascular perfusions and in isolated liver cell assays. RESULTS: Des-R(9)-BK did not elicit a portal hypertensive response (PHR); BK infused into the hepatic artery elicited a calcium-dependent PHR and a calcium-independent arterial hypertensive response (HAHR), with the latter being almost abolished by naproxen. BK has a predominant distribution in the extracellular space and an average hepatic extraction of 8% in the steady state. Hydrolysis products of infused BK (R(1)-F(5) and R(1)-P(7)) did not elicit PHR. Angiotensin converting enzyme (ACE) is concentrated in the perivenous region and B2R in the periportal region. Microphysiometry showed that BK (and not a B1 agonist) interacts with stellate cells and the endothelial sinusoidal/Kupffer cell fraction. This effect was inhibited by the B2R antagonist. CONCLUSIONS: Events can be summarized as: the hypertensive action of BK on sinusoidal cells of the periportal region is followed by its hydrolysis by ACE which is primarily present in the perivenous region; there is no functional B1R in the normal liver; BK induces HAHR via eicosanoid release and PHR by a distinct pathway on the B2R. Our data suggest that BK may participate in the modulation of sinusoidal microvasculature tonus both in the portal and the arterial routes.

Hemodynamic and metabolic effects of angiotensin II on the liver.

To ascertain the mechanism of interaction between angiotensins (AI and AII) and the liver, an angiotensin-converting enzyme inhibitor (captopril) and a receptor antagonist (losartan) were used. Monovascular or bivascular liver perfusion was used to assess both hemodynamic (portal and arterial hypertensive responses) and metabolic (glucose production and oxygen consumption) effects. Microphysiometry was used for isolated liver cell assays to assess AII or losartan membrane receptor-mediated interaction. Captopril abolishes portal hypertensive response (PHR) to AI but not the AII effect. AII infused via the portal pathway promotes calcium-dependent PHR but not a hypertensive response in the arterial pathway (AHR); when infused into the arterial pathway AII promotes calcium-dependent PHR and AHR. Losartan infused into the portal vein abolishes PHR to AII but not the metabolic response; when infused via both pathways it abolishes the hypertensive responses and inhibits the metabolic effects. Isolated liver cells specifically respond to AII. Sinusoidal cells, but not hepatocytes, respond to 10 nM losartan. We conclude that AI has to be converted to AII to produce PHR. Quiescent stellate cells interacts in vitro with AII and losartan. Hemodynamic responses to AII are losartan-dependent but metabolic responses are partially losartan-independent. AII hemodynamic actions are mainly presinusoidal.

Localization of EP24.15, a major liver kininase.

The liver is important for the kallikrein-kinin system modulation. This system plays a role in the inflammatory cascade with anticoagulant, profibrinolytic, and anti-adhesive attributes. The metalloendopeptidase EP24.15 is a major hepatic kininase. We studied the tissue distribution and subcellular localization of this enzyme in rat liver by cell fractionation and immunohistochemistry. Our results showed that EP24.15 is predominant in the soluble fraction of the liver homogenate and is present in the cytoplasm of hepatocytes, particularly in the perivenous zone (Z3). This localization is relevant because most hepatotoxin-induced necrosis, as well as ischemic hepatocellular injury, is predominant in Z3.

Ação hemodinâmica e metabolismo da bradicinina no fígado / Hemodynamic action and metabolism of bradykinin on the liver

Bradicinina (R1P2P3G4S6P7F8R9) infundida na veia porta provoca resposta hipertensiva via receptor B2 e, por outro lado, é eficientemente hidrolisada pelo fígado. A EC 3.4.24.15 é a principal enzima inativadora de BK in vitro e é liberada de fígados normais preservados ex vivo em líquido Braun Collins. Nossos objetivos foram: 1) estudar a liberação da EC 3.4.24.15 no reperfusato de fígados (normais e em fase aguda de inflamação) preservados ex vivo; 2) localizar a EC 3.4.24.15 no fígado; 3) caracterizar a interação entre bradicinina (BK) e fígado eluciando o local da ação do peptídeo e o papel das cininases ECA (enzima conversora de angiotensina) e EC 3.4.24.15 na sua inativação. Para tanto, fígados normais e inflamados foram preservados em líquido University of Wisconsin e reperfundidos após 8 ou 24 h. Alíquotas do reperfusato foram recolhidas para dosagens enzimáticas. BK, antagonista do receptor B2 (HOE-140), agonista do receptor B1 (des-R9-BK) e inibidores enzimáticos foram utilizados em perfusões monovascular (entrada pela veia porta) e bivascular (entrada pela veia porta e artéria hepática) de fígado e em ensaios com células hepáticas isoladas. Verificamos que a liberação da EC 3.4.24.15 no reperfusato de figados inflamados foi superior aos normais. Des-R9-BK não produz resposta hipertensiva portal (RHP); BK infundida na artéria hepática provocou RHP (cálcio-dependente) e resposta hipertensiva arterial (RHA) (cálcio-independente), esta quase abolida por naproxeno. Os produtos de hidrólise da BK infundida são R1-F5 e R1-P7; estes fragmentos não foram capazes de produzir RHP. ECA e EC 3.4.24.15 estão presentes no fígado e concentram-se na região perivenular (imuno-histoquímica); BK tem distribuição predominante no espaço extracelular e média de extração hepática de 8 por cento em condições estacionárias (diluição de indicadores); o receptor B2 concentra-se na região periportal em células sinusoidais (imuno-histoquímica), resultado confirmado com Cytosensor microphysiometer onde BK (mas não des-R9-BK) elicia mudanças na taxa de acidificação basal de células estreladas e da fração contendo células sinusoidais endoteliais/Kupffer, este efeito é inibido por HOE-140. Concluímos que a EC3.4.24.15 é indicador sensível do estado inflamatório de fígados preservados mas não indica disfunção do órgão; a seqüência de eventos é ação hipertensiva da BK em células sinusoidais da região periportal e sua hidrólise pela ECA e não pela EC 3.4.24.15...

Enzyme release from injured, preserved, and ex vivo reperfused liver does not indicate malfunction.

OBJECTIVE: We compared the enzyme release from preserved and ex vivo reperfused livers after acute injury or inflammatory stimulus with organ function. METHODS: Acute injury was induced by carbon tetrachloride and inflammation was induced by turpentine oil treatments. Livers were exsanguinated and preserved for 8 or 24 hr. Enzymes were measured in preservation and reperfusion solutions, and reperfused liver function was evaluated by O(2) consumption and bromsulphalein clearance. RESULTS: The release of lysosomal enzymes was negligible in the preservation solution, and that of alanine aminotransferase and lactate dehydrogenase was similar in all groups. Release of aspartate aminotransferase and of EC 3.4.24.15 was more than that of the controls. During reperfusion liver function was normal in the injured group. CONCLUSION: Release of enzymes, mainly aspartate aminotransferase and EC 3.4.24.15, into the preservation solution is a sensitive and early indicator of either inflammatory or acute injury alterations of the preserved liver, but does not reflect organ malfunction.