Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure

After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1â (3.8X) and TNF-á (6.0X). IFN-ã was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.

Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure.

After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1beta (3.8X) and TNF-alpha (6.0X). IFN-gamma was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.

Efficacy of a diagnostic strategy for patients with chest pain and no ST-segment elevation in the emergency room.

PURPOSE: To evaluate the efficacy of a systematic model of care for patients with chest pain and no ST segment elevation in the emergency room. METHODS: From 1003 patients submitted to an algorithm diagnostic investigation by probability of acute ischemic syndrome. We analyzed 600 ones with no elevation of ST segment, then enrolled to diagnostic routes of median (route 2) and low probability (route 3) to ischemic syndrome. RESULTS: In route 2 we found 17% acute myocardial infarction and 43% unstable angina, whereas in route 3 the rates were 2% and 7%, respectively. Patients with normal/non-specific ECG had 6% probability of AMI whereas in those with negative first CKMB it was 7%; the association of the 2 data only reduced it to 4%. In patients in route 2 the diagnosis of AMI could only be ruled out with serial CKMB measurement up to 9 hours, while in route 3 it could be done in up to 3 hours. Thus, sensitivity and negative predictive value of admission CKMB for AMI were 52% and 93%, respectively. About one-half of patients with unstable angina did not disclose objective ischemic changes on admission. CONCLUSION: The use of a systematic model of care in patients with chest pain offers the opportunity of hindering inappropriate release of patients with ACI and reduces unnecessary admissions. However some patients even with normal ECG should not be released based on a negative first CKMB. Serial measurement of CKMB up to 9 hours is necessary in patients with medium probability of AMI.

Chest pain in the emergency room. Importance of a systematic approach.

OBJECTIVE: To evaluate the efficiency of a systematic diagnostic approach in patients with chest pain in the emergency room in relation to the diagnosis of acute coronary syndrome (ACS) and the rate of hospitalization in high-cost units. METHODS: One thousand and three consecutive patients with chest pain were screened according to a preestablished process of diagnostic investigation based on the pre-test probability of ACS determinate by chest pain type and ECG changes. RESULTS: Of the 1003 patients, 224 were immediately discharged home because of no suspicion of ACS (route 5) and 119 were immediately transferred to the coronary care united because of ST elevation or left bundle-branch block (LBBB) (route 1) (74% of these had a final diagnosis of acute myocardial infarction [AMI]). Of the 660 patients that remained in the emergency room under observation, 77 (12%) had AMI without ST segment elevation and 202 (31%) had unstable angina (UA). In route 2 (high probability of ACS) 17% of patients had AMI and 43% had UA, whereas in route 3 (low probability) 2% had AMI and 7% had UA. The admission ECG has been confirmed as a poor sensitivity test for the diagnosis of AMI (49%), with a positive predictive value considered only satisfactory (79%). CONCLUSION: A systematic diagnostic strategy, as used in this study, is essential in managing patients with chest pain in the emergency room in order to obtain high diagnostic accuracy, lower cost, and optimization of the use of coronary care unit beds.

[Hospital outcome and short-term follow-up of elderly patients presenting to the emergency unit with congestive heart failure]. / Evolução intra-hospitalar e seguimento pós-alta de pacientes idosos atendidos com insuficiência cardíaca congestiva na unidade de emergência.

PURPOSE: To evaluate the in-hospital (IH) outcome and the short-term follow-up of predominantly elderly patients presenting to an emergency room (ER) with congestive heart failure (CHF). METHODS: In an 11 month period, 57 patients presenting to the ER with CHF were included. Mean age was 69 +/- 15 years (27 to 94) and 39 (68.4%) were male. CHF diagnosis was based on the Boston criteria. We evaluated IH outcome and prognosis in a mean follow-up of 5.7 +/- 2.7 months (1 to 12). In addition, some mortality predictors and mechanisms of death according on the ACME system were identified. RESULTS: Eight patients (14%) died in the IH period. Modes of death were circulatory failure (CF) in 7, and peri-operative (PO) in one (aortic valve replacement). During follow-up 9 deaths occurred. Five were due to CF, 2 were sudden and 2 were PO (mitral valve replacement and ventriculectomy). Six-months and 1-year survival rates of the patients who were discharged were 82% and 66%, respectively. Sodium lower than 135 mEq/l (p = 0.004) and female gender (p = 0.038) were independent predictors of mortality. CONCLUSION: Elderly patients with CHF admitted to the ER have high in-hospital and short-term follow up mortalities. The majority die from CF due to worsening heart failure.

Evoluçäo intra-hospitalar e seguimento pós-alta de pacientes idosos atendidos com insuficiência cardíaca congestiva na unidade de emergência / Hospital outcome and short-term follow-up of predominatly elderly patients presenting to the emergency department with congestive heart failure

OBJETIVO - Conhecer a evoluçäo intra-hospitalar (IH) e pós-alta (PA) de uma populaçäo predominantemente idosa, com insuficiência cardíaca congestiva (ICC) na unidade de emergência (UE). MÉTODOS - Durante 11 meses, foram selecionados 57 pacientes consecutivos com ICC, atendidos em UE, com idade média de 69ñ15 (27 a 94) anos, sendo 39 (68,4 por cento) homens. O diagnóstico de ICC baseou-se nos critérios de Boston. Avaliou-se a evoluçäo IH e PA num período médio de 5,7ñ2,7 (1 A 12) meses, procurando-se identificar variáveis que se correlacionassem com a mortalidade e o mecanismo de morte, avaliado pelo sistema ACME. RESULTADOS - Oito (14 por cento) pacientes faleceram na fase IH, sendo 7 por falência circulatória (FC), e 1 em pós-operatório (PO). Durante o seguimento ocorreram 9 (18,4 por cento) óbitos, sendo 5 por FC, 2 mortes súbitas e 2 em (troca valvar mitral e ventriculectomia). A sobrevida dos pacientes...

[Hospital mortality in acute myocardial infarction: is it possible to predict using admission data?]. / Mortalidade hospitalar no infarto agudo do miocárdio: E possível prever utilizando dados de admissão?

PURPOSE: To identify clinical variables on admission that are related to hospital mortality in acute myocardial infarction (AMI) and to generate a mathematic model to predict accurately this mortality. METHODS: Prospective study with 347 consecutive patients with AMI in which clinical variables related to mortality were identified by univariate and multivariate analysis. The mathematic model generated by multivariate logistic regression analysis was applied in each patient to determine his/her probability (P) of hospital death. Model's accuracy was validated by reliability and discrimination tests. RESULTS: Admission variables directly and independently related to hospital mortality: female gender, age, absence of history of hypertension, history of previous infarction, non-inferior AMI and Killip class. These six variables, when present cumulatively, showed increasing mortality rates. Mean P value for non-survivors was significantly greater than for survivors (43.2 +/- 31.4% vs 9.1 +/- 12.5%, p < 0.00001). Reliability of the model to predict death, assessed by stratifying patients in three risk groups (low, medium and high) or continuously (by linear regression analysis) showed excellent predictive performance. Discrimination between survivors and non-survivors, assessed by C-index (concordance probability), disclosed 85% rate of success. CONCLUSION: Risk variables can be used in a mathematic model that is capable of predicting accurately in-hospital mortality of each patient with AMI. Mortality prediction can allow physicians to be more efficient in assessing risk-benefit ratios in these patients when faced with therapeutic decisions.

[Torsades de pointes: analysis of 105 episodes]. / Torsades de pointes: análise de 105 episódios.

PURPOSE: To analyze episodes of Torsades de Pointes (TP), in search of its electrocardiographic characteristics. PATIENTS AND METHODS: We analyzed 105 episodes of TP, in 4 patients using quinidine and diuretics, recorded by 24-hour Holter monitoring. The following parameters were studied; ventricular repolarization out of TP, rhythm disturbances before TP; ECG characteristics of the onset, the bouts and the end of the TP. RESULTS: Ventricular repolarization, out of the TP, was abnormal, with the presence of U-waves at the end of the T-waves, resulting in prolongation of the QT (QU) interval. The U-wave voltage was noted to be cycle-length dependent. Ventricular bigeminy preceded TP in 100 episodes (95%) and the mean interval between both parameters was 18 +/- 16 min. The onset of the TP episodes showed the "short/long/short cycle rule", hereby called "pre-pause cycle", "preparing cycle" and "trigger cycle" respectively. The rotatory QRS-T morphology around the baseline, was seen in 75% of episodes, at the beginning or throughout the bout. Monomorphic ventricular tachycardia pattern was seen in the other 25% of episodes. Termination of bouts was sudden in all cases, and persistent ventricular bigeminy led to another bout in 90 episodes (85%). CONCLUSION: In TP patients, there is enlargement of QT intervals mostly due to U-waves appearance. The U-waves seen in these cases, probably have an important role in the genesis of TP and are probably related to ventricular after-potentials (triggered activity). Ventricular bigeminy is a premonitory sign of TP in patients using class 1A antiarrhythmic drugs. Persistent ventricular bigeminy post-TP episodes is a strong indicator of another bout of TP. The onset of TP is more important than its morphology for the correct diagnosis of this arrhythmia.

[Torsades de Pointes: analysis of 105 episodes]. / Torsades de Pointes: análise de 105 episódios.

PURPOSE: To analyze episodes of Torsades de Pointes (TP), in search of its electrocardiographic characteristics. PATIENTS AND METHODS: We analyzed 105 episodes of TP, in 4 patients using quinidine and diuretics, recorded by 24-hour Holter monitoring. The following parameters were studied; ventricular repolarization out of TP, rhythm disturbances before TP; EKG characteristics of the onset, the bouts and the end of the TP. RESULTS: Ventricular repolarization, out of the TP, was abnormal, with the presence of U-waves at the end of the T-waves, resulting in prolongation of the QT (QU) interval. The U-wave voltage was noted to be cycle-length dependent. Ventricular bigeminy preceded TP in 100 episodes (95%) and the mean interval between both parameters was 18 +/- 16 min. The onset of the TP episodes showed the "short/long/short cycle rule", hereby called "pre-pause cycle", "preparing cycle" and "trigger cycle" respectively. The rotatory QRS-T morphology around the baseline, was seen in 75% of episodes, at the beginning or throughout the bout. Monomorphic ventricular tachycardia pattern was seen in the other 25% of episodes. Termination of bouts was sudden in all cases, and persistent ventricular bigeminy led to another bout in 90 episodes (85%). CONCLUSION: In TP patients, there is enlargement of QT intervals mostly due to U-waves appearance. The U-waves seen in these cases, probably have an important role in the genesis of TP and are probably related to ventricular after-potentials (triggered activity). Ventricular bigeminy is a premonitory sign of TP in patients using class 1A antiarrhythmic drugs. Persistent ventricular bigeminy post-TP episodes is a strong indicator of another bout of TP. The onset of TP is more important than its morphology for the correct diagnosis of this arrhythmia.