Natriuretic Peptides and Long-Term Mortality in Patients with Severe Aortic Stenosis

Background and aim of the study: The natriuretic peptides, brain natriuretic peptide (BNP) and its N-terminal prohormone (NT-proBNP), can be used as diagnostic and prognostic markers for aortic stenosis (AS). However, the association between BNP, NT-proBNP, and long-term clinical outcomes in patients with severe AS remains uncertain. Methods: A total of 64 patients with severe AS was prospectively enrolled into the study, and underwent clinical and echocardiographic assessments at baseline. Blood samples were drawn for plasma BNP and NT-proBNP analyses. The primary outcome was death from any cause, through a six-year follow up period. Cox proportional hazards modeling was used to examine the association between natriuretic peptides and long-term mortality, adjusting for important clinical factors. Results: During a mean period of 1,520 681 days, 51 patients (80%) were submitted to aortic valve replacement, and 13 patients (20%) were medically managed without surgical interventions. Mortality rates were 13.7% in the surgical group and 62% in the medically managed group (p <0.001). Patients with higher plasma BNP (>135 pg/ml) and NT-proBNP (>1,150 pg/ml) levels at baseline had a greater risk of long-term mortality (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.1-9.1; HR 4.3, 95% CI 1.4-13.5, respectively). After adjusting for important covariates, both BNP and NT-proBNP remained independently associated with long-term mortality (HR 2.9, 95%CI 1.5-5.7; HR 1.8, 95%CI 1.1-3.1, respectively). Conclusion: In patients with severe AS, plasma BNP and NT-proBNP levels were associated with long-term mortality. The use of these biomarkers to guide treatment might represent an interesting approach that deserves further evaluation. The Journal of Heart Valve Disease 2012;21:331-336

The Real Importance of Pre-Existing Comorbidities on Long-Term Mortality after Acute Kidney Injury

Background: The causes of death on long-term mortality after acute kidney injury (AKI) have not been well studied. The purpose of the study was to evaluate the role of comorbidities and the causes of death on the long-term mortality after AKI. Methodology/Principal Findings: We retrospectively studied 507 patients who experienced AKI in 2005-2006 and were discharged free from dialysis. In June 2008 (median: 21 months after AKI), we found that 193 (38%) patients had died. This mortality is much higher than the mortality of the population of Sao Paulo City, even after adjustment for age. A multiple survival analysis was performed using Cox proportional hazards regression model and showed that death was associated with Khan's index indicating high risk [adjusted hazard ratio 2.54 (1.38-4.66)], chronic liver disease [1.93 (1.15-3.22)], admission to non-surgical ward [1.85 (1.30-2.61)] and a second AKI episode during the same hospitalization [1.74 (1.12-2.71)]. The AKI severity evaluated either by the worst stage reached during AKI (P=0.20) or by the need for dialysis (P=0.12) was not associated with death. The causes of death were identified by a death certificate in 85% of the non-survivors. Among those who died from circulatory system diseases (the main cause of death), 59% had already suffered from hypertension, 34% from diabetes, 47% from heart failure, 38% from coronary disease, and 66% had a glomerular filtration rate <60 previous to the AKI episode. Among those who died from neoplasms, 79% already had the disease previously. Conclusions: Among AKI survivors who were discharged free from dialysis the increased long-term mortality was associated with their pre-existing chronic conditions and not with the severity of the AKI episode. These findings suggest that these survivors should have a medical follow-up after hospital discharge and that all efforts should be made to control their comorbidities.

Long-Term Follow-Up of Patients after Acute Kidney Injury: Patterns of Renal Functional Recovery

Background and Objectives: Patients who survive acute kidney injury (AKI), especially those with partial renal recovery, present a higher long-term mortality risk. However, there is no consensus on the best time to assess renal function after an episode of acute kidney injury or agreement on the definition of renal recovery. In addition, only limited data regarding predictors of recovery are available. Design, Setting, Participants, & Measurements: From 1984 to 2009, 84 adult survivors of acute kidney injury were followed by the same nephrologist (RCRMA) for a median time of 4.1 years. Patients were seen at least once each year after discharge until end stage renal disease (ESRD) or death. In each consultation serum creatinine was measured and glomerular filtration rate estimated. Renal recovery was defined as a glomerular filtration rate value >= 60 mL/min/1.73 m2. A multiple logistic regression was performed to evaluate factors independently associated with renal recovery. Results: The median length of follow-up was 50 months (30-90 months). All patients had stabilized their glomerular filtration rates by 18 months and 83% of them stabilized earlier: up to 12 months. Renal recovery occurred in 16 patients (19%) at discharge and in 54 (64%) by 18 months. Six patients died and four patients progressed to ESRD during the follow up period. Age (OR 1.09, p < 0.0001) and serum creatinine at hospital discharge (OR 2.48, p = 0.007) were independent factors associated with non renal recovery. The acute kidney injury severity, evaluated by peak serum creatinine and need for dialysis, was not associated with non renal recovery. Conclusions: Renal recovery must be evaluated no earlier than one year after an acute kidney injury episode. Nephrology referral should be considered mainly for older patients and those with elevated serum creatinine at hospital discharge.

Long-Term Follow-Up of Implantable Cardioverter-Defibrillator for Secondary Prevention in Chagas' Heart Disease

Assessing the efficacy of implantable cardioverter-defibrillators (ICD) in patients with Chagas' heart disease (ChHD) and identifying the clinical predictors of mortality and ICD shock during long-term follow-up. ChHD is associated with ventricular tachyarrhythmias and an increased risk of sudden cardiac death. Although ChHD is a common form of cardiomyopathy in Latin American ICD users, little is known about its efficacy in the treatment of this population. The study cohort included 116 consecutive patients with ChHD and an ICD implanted for secondary prevention. Of the 116 patients, 83 (72%) were men; the mean age was 54 +/- 10.7 years. Several clinical variables were tested in a multivariate Cox model for predicting long-term mortality. The average follow-up was 45 +/- 32 months. New York Heart Association class I-II developed in 83% of patients. The mean left ventricular ejection fraction was 42 +/- 16% at implantation. Of the 116 patients, 58 (50%) had appropriate shocks and 13 (11%) had inappropriate therapy. A total of 31 patients died (7.1% annual mortality rate). New York Heart Association class III (hazard ratio [HR] 3.09, 95% confidence interval 1.37 to 6.96, p = 0.0064) was a predictor of a worse prognosis. The left ventricular ejection fraction (HR 0.972, 95% confidence interval 0.94 to 0.99, p = 0.0442) and low cumulative right ventricular pacing (HR 0.23, 95% confidence interval 0.11 to 0.49, p = 0.0001) were predictors of better survival. The left ventricular diastolic diameter was an independent predictor of appropriate shock (I-ER 1.032, 95% confidence interval 1.004 to 1.060, p = 0.025). In conclusion, in a long-term follow-up, ICD efficacy for secondary sudden cardiac death prevention in patients with ChHD was marked by a favorable annual rate of all-cause mortality (7.1%); 50% of the cohort received appropriate shock therapy. New York Heart Association class III and left ventricular ejection fraction were independent predictors of worse prognosis, and low cumulative right ventricular pacing defined better survival. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1040-1045)

Long-Term Prospective Study of the Influence of Estrone Levels on Events in Postmenopausal Women with or at High Risk for Coronary Artery Disease

Background. The link between endogenous estrogen, coronary artery disease (CAD), and death in postmenopausal women is uncertain. We analyzed the association between death and blood levels of estrone in postmenopausal women with known coronary artery disease (CAD) or with a high-risk factor score for CAD. Methods. 251 postmenopausal women age 50-90 years not on estrogen therapy. Fasting blood for estrone and heart disease risk factors were collected at baseline. Women were grouped according to their estrone levels (<15 and >= 15 pg/mL). Fatal events were recorded after 5.8 perpendicular to 1.4 years of followup. Results. The Kaplan-Meier survival curve showed a significant trend (P = 0.039) of greater all-cause mortality in women with low estrone levels (< 15 pg/mL). Cox multivariate regression analysis model adjusted for body mass index, diabetes, dyslipidemia, family history, and estrone showed estrone (OR = 0.45; P = 0.038) as the only independent variable for all-cause mortality. Multivariate regression model adjusted for age, body mass index, hypertension, diabetes, dyslipidemia, family history, and estrone showed that only age (OR = 1.06; P = 0.017) was an independent predictor of all-cause mortality. Conclusions. Postmenopausal women with known CAD or with a high-risk factor score for CAD and low estrone levels (< 15 pg/mL) had increased all-cause mortality.

Does anti-hepatitis B virus vaccine make any difference in long-term number of liver transplantation?

Background: Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality worldwide. Chronic hepatitis B infection is associated with an increased risk of cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Our aim is to analyze, through a mathematical model, the potential impact of anti-HBV vaccine in the long-term (that is, decades after vaccination) number of LT. Methods: The model simulated that the prevalence of HBV infection was 0.5% and that approximately 20% of all the liver transplantation carried out in the state of Sao Paulo are due to HBV infection. Results: The theoretical model suggests that a vaccination program that would cover 80% of the target population would reach a maximum of about 14% reduction in the LT program. Conclusion: Increasing the vaccination coverage against HBV in the state of Sao Paulo would have a relatively low impact on the number of liver transplantation. In addition, this impact would take several decades to materialize due to the long incubation period of liver failure due to HBV.

Predictors of long-term survival among first-ever ischemic and hemorrhagic stroke in a Brazilian stroke cohort

Abstract Background Few studies have examined both ischemic and hemorrhagic stroke to identify prognostic factors associated to long-term stroke survival. We investigated long-term survival and predictors that could adversely influence ischemic and hemorrhagic first-ever stroke prognosis. Methods We prospectively ascertained 665 consecutive first-ever ischemic and hemorrhagic stroke cases from “The Study of Stroke Mortality and Morbidity” (The EMMA Study) in a community hospital in São Paulo, Brazil. We evaluated cardiovascular risk factors and sociodemographic characteristics (age, gender, race and educational level). Results We found a lower survival rate among hemorrhagic cases compared to ischemic stroke cases at the end of 4 years of follow-up (52% vs. 44%, p = 0.04). The risk of death was two times higher among people with ischemic stroke without formal education. Also, we found consistently higher risk of death for diabetics with ischemic stroke (HR = 1.45; 95% CI = 1.07-1.97) compared to no diabetics. As expected, age equally influenced on the high risk of poor survival, regardless of stroke subtype. Conclusions For ischemic stroke, the lack of formal education and diabetes were significant independent predictors of poor long-term survival.

IFN-γ-induced priming maintains long-term strain-transcending immunity against blood-stage Plasmodium chabaudi malaria

The mechanism by which protective immunity to Plasmodium is lost in the absence of continued exposure to this parasite has yet to be fully elucidated. It has been recently shown that IFN-γ produced during human and murine acute malaria primes the immune response to TLR agonists. In this study, we investigated whether IFN-γ-induced priming is important to maintain long-term protective immunity against Plasmodium chabaudi AS malaria. On day 60 postinfection, C57BL/6 mice still had chronic parasitemia and efficiently controlled homologous and heterologous (AJ strain) challenge. The spleens of chronic mice showed augmented numbers of effector/effector memory (TEM) CD4(+) cells, which is associated with increased levels of IFN-γ-induced priming (i.e., high expression of IFN-inducible genes and TLR hyperresponsiveness). After parasite elimination, IFN-γ-induced priming was no longer detected and protective immunity to heterologous challenge was mostly lost with >70% mortality. Spontaneously cured mice had high serum levels of parasite-specific IgG, but effector T/TEM cell numbers, parasite-driven CD4(+) T cell proliferation, and IFN-γ production were similar to noninfected controls. Remarkably, the priming of cured mice with low doses of IFN-γ rescued TLR hyperresponsiveness and the capacity to control heterologous challenge, increasing the TEM cell population and restoring the CD4(+) T cell responses to parasites. Contribution of TLR signaling to the CD4(+) T cell responses in chronic mice was supported by data obtained in mice lacking the MyD88 adaptor. These results indicate that IFN-γ-induced priming is required to maintain protective immunity against P. chabaudi and aid in establishing the molecular basis of strain-transcending immunity in human malaria.

Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction

BACKGROUND: Ischemia and reperfusion (IR) injury remains a major cause of morbidity and mortality and multiple molecular and cellular pathways have been implicated in this injury. We determined whether acute inhibition of excessive mitochondrial fission at the onset of reperfusion improves mitochondrial dysfunction and cardiac contractility postmyocardial infarction in rats. METHODS AND RESULTS: We used a selective inhibitor of the fission machinery, P110, which we have recently designed. P110 treatment inhibited the interaction of fission proteins Fis1/Drp1, decreased mitochondrial fission, and improved bioenergetics in three different rat models of IR, including primary cardiomyocytes, ex vivo heart model, and an in vivo myocardial infarction model. Drp1 transiently bound to the mitochondria following IR injury and P110 treatment blocked this Drp1 mitochondrial association. Compared with control treatment, P110 (1 μmol/L) decreased infarct size by 28 ± 2% and increased adenosine triphosphate levels by 70+1% after IR relative to control IR in the ex vivo model. Intraperitoneal injection of P110 (0.5 mg/kg) at the onset of reperfusion in an in vivo model resulted in improved mitochondrial oxygen consumption by 68% when measured 3 weeks after ischemic injury, improved cardiac fractional shortening by 35%, reduced mitochondrial H2O2 uncoupling state by 70%, and improved overall mitochondrial functions. CONCLUSIONS: Together, we show that excessive mitochondrial fission at reperfusion contributes to long-term cardiac dysfunction in rats and that acute inhibition of excessive mitochondrial fission at the onset of reperfusion is sufficient to result in long-term benefits as evidenced by inhibiting cardiac dysfunction 3 weeks after acute myocardial infarction.