The role of N-terminal PRO-brain natriuretic peptide and echocardiography for screening asymptomatic left ventricular dysfunction in a population at high risk for heart failure. The PROBE-HF study.

BACKGROUND: Screening for asymptomatic left ventricular dysfunction (ALVD) in subjects at risk for heart failure (HF) can affect clinical management. The aim of the present study is to examine the role of NT-pro BNP in the diagnosis of ALVD in subjects with hypertension and diabetes from primary care. METHODS AND RESULTS: A total of 1012 subjects with hypertension and/or diabetes and no symptoms or signs of HF were assessed by B-type natriuretic peptide (NT-proBNP) assay and echocardiography. Diastolic dysfunction was present in 368/1012 subjects (36.4%): 327 (32.4%) with mild diastolic dysfunction and 41 (4%) with a moderate-to-severe diastolic dysfunction. Systolic dysfunction was present in 11/1012 (1.1%). NT-proBNP levels were 170 +/- 206 and 859 +/- 661 pg/mL, respectively, in diastolic and systolic dysfunction and 92 +/- 169 in normal subjects (P < .0001). Pooling moderate-to-severe diastolic with systolic dysfunction, a total of 52 subjects (5.1 %) were obtained: best cutoff value of NT-proBNP was 125 pg/mL (males <67 years: sensitivity [Sens] 87.5%, specificity [Spec] 92.7%, negative predictive value [NPV] 99.5%, positive predictive value [PPV] 33.3%; females <67 years: Sens 100%, Spec 84.1%, NPV 100%, PPV 33.3%; males >or=67 years: Sens 100%, Spec 77.1%, NPV 100%, PPV 32.5%; females >or=67 years: Sens 100%, Spec 59.9%, NPV 100%, PPV 23%). CONCLUSIONS: The prevalence of ALVD in subjects at risk for HF is 5.1%. Because of its excellent NPV, NT-proBNP can be used by general practitioners to rule out ALVD in hypertensive or diabetic patients.

Spatial relationship between coronary microvascular dysfunction and delayed contrast enhancement in patients with hypertrophic cardiomyopathy.

UNLABELLED: To clarify the spatial relationship between coronary microvascular dysfunction and myocardial fibrosis in hypertrophic cardiomyopathy (HCM), we compared the measurement of hyperemic myocardial blood flow (hMBF) by PET with the extent of delayed contrast enhancement (DCE) detected by MRI. METHODS: In 34 patients with HCM, PET was performed using (13)N-labeled ammonia during hyperemia induced by intravenous dipyridamole. DCE and systolic thickening were assessed by MRI. Left ventricular myocardial segments were classified as with DCE, either transmural (DCE-T) or nontransmural (DCE-NT), and without DCE, either contiguous to DCE segments (NoDCE-C) or remote from them (NoDCE-R). RESULTS: In the group with DCE, hMBF was significantly lower than in the group without DCE (1.81 +/- 0.94 vs. 2.13 +/- 1.11 mL/min/g; P < 0.001). DCE-T segments had lower hMBF than did DCE-NT segments (1.43 +/- 0.52 vs. 1.91 +/- 1 mL/min/g, P < 0.001). Similarly, NoDCE-C segments had lower hMBF than did NoDCE-R (1.98 +/- 1.10 vs. 2.29 +/- 1.10 mL/min/g, P < 0.01) and had no significant difference from DCE-NT segments. Severe coronary microvascular dysfunction (hMBF in the lowest tertile of all segments) was more prevalent among NoDCE-C than NoDCE-R segments (33% vs. 24%, P < 0.05). Systolic thickening was inversely correlated with percentage transmurality of DCE (Spearman rho = -0.37, P < 0.0001) and directly correlated with hMBF (Spearman rho = 0.20, P < 0.0001). CONCLUSION: In myocardial segments exhibiting DCE, hMBF is reduced. DCE extent is inversely correlated and hMBF directly correlated with systolic thickening. In segments without DCE but contiguous to DCE areas, hMBF is significantly lower than in those remote from DCE and is similar to the value obtained in nontransmural DCE segments. These results suggest that increasing degrees of coronary microvascular dysfunction might play a causative role for myocardial fibrosis in HCM.

Prognostic role of N-terminal pro-brain natriuretic peptide in asymptomatic hypertensive and diabetic patients in primary care: impact of age and gender : Results from the PROBE-HF study.

BACKGROUND: The association between natriuretic peptides and clinical outcome in asymptomatic hypertensive and diabetic patients with no clinical evidence of heart failure (HF) is still unclear. We assessed the prognostic value of NT-pro BNP, and its interactions with age and gender, in a cohort of asymptomatic, stage A/B HF hypertensive and diabetic patients enrolled in primary care. METHODS: NT-proBNP was measured in 1012 asymptomatic subjects with systemic hypertension and/or type-2 diabetes (age 66.6 ± 7.8 years, 48 % males) with no clinical evidence of HF. Patients were prospectively followed over 49.8 ± 6.7 months for the development of cardiac death, HF hospitalization, and nonfatal myocardial infarction. RESULTS: Patients with NT-proBNP above the 80th age- and gender-specific percentile showed a threefold risk of events as compared to those with NT-proBNP under this cut-off [hazard ratio 3.2 (2.6-8.3), p < 0.0001]. In multivariable analysis, NT-proBNP added independent and incremental prognostic information to a predictive model including established risk factors (p < 0.0001). After stratification by age, increased NT-proBNP predicted outcome among patients in the second and third age tertiles, but not among those in the first tertile. Increased NT-proBNP was associated with a 3.6-fold risk in women and a 2.9-fold risk in men. Addition of the gender-NT-proBNP interaction to prognostic models further improved prediction of events (p = 0.014). CONCLUSIONS: NT-proBNP measurement adds independent and incremental information for the prediction of clinical outcome in asymptomatic, stage A-B HF hypertensive and diabetic patients taken from primary care. This prognostic value might be further evident in the elderly and among women.

Current perspective the expanding role of cardiovascular magnetic resonance in the identification of myocardial viability.

Cardiovascular magnetic resonance (CMR) is becoming a widespread diagnostic tool available to cardiologists to image different cardiovascular diseases. Among the main applications CMR has proven to be useful in the evaluation of patients with coronary artery disease. Particularly important seems the evaluation of coronary artery disease patients with left ventricular dysfunction. As a matter of fact CMR can identify myocardial viability by using different methods. CMR can accurately measure diastolic wall thickness and demonstrate a contractile reserve in segments with wall motion abnormalities when coupled to low-dose dobutamine infusion. In both applications CMR has proven to be superior to other diagnostic tools that use the same target of viability. By using gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) administration it has recently been shown that CMR can accurately detect myocardial viability. In fact, irreversibly damaged myocardial segments show a delayed hyperenhancement compared to normal segments. Due to its excellent spatial resolution one of the most important information that CMR offers in this application is the transmural extent of necrosis/viability that no other method can offer. The available data suggest that Gd-DTPA CMR could be superior to any other currently used methods in the identification of both stunning and hibernation.

Hyperhomocysteinemia and vitamin B6 deficiency: new risk markers for nonvalvular atrial fibrillation?

BACKGROUND: A recent "ex-vivo" study showed that nonvalvular atrial fibrillation (NVAF) is associated with enhanced activity of metalloproteinases at the atrial level, and in animal models homocysteine (Hcy) is able to activate metalloproteinases. The aim of this case-control study was to investigate the association of total Hcy plasma levels, vitamin status (folate, vitamin B6, and vitamin B12), and methylenetetrahydrofolate reductase C677T and CBS 844ins68 polymorphisms with NVAF. Furthermore, the role of these variables in the occurrence of ischemic events was investigated. METHODS: We studied 310 NVAF patients on oral anticoagulant treatment (168 patients with previous ischemic events and 142 without) and 310 controls. RESULTS: Hyperhomocysteinemia (highest quartile) and vitamin B6 deficiency (lowest quartile) were independently associated with NVAF after multivariate analysis (Hcy: odds ratio [OR] 6.40, 95% CI 3.29-12.46; vitamin B6: OR 3.02, 95% CI 1.02-8.95). A significant correlation was found between Hcy levels and left atrial diameter (r = 0.46; P <.001). As shown by multivariate analysis, elevated Hcy levels were an independent risk factor for ischemic complications during NVAF (OR 2.66, 95% CI 1.15-6.20). CONCLUSIONS: This study demonstrates a significant association of both elevated Hcy levels and low vitamin B6 levels with the presence of NVAF; in addition, it confirms the role of Hcy as a risk factor for ischemic events during NVAF.

Thrombophilic mutations in high-risk atrial fibrillation patients: high prevalence of prothrombin gene G20210A polymorphism and lack of correlation with thromboembolism.

Atrial fibrillation (AF) is a common arrhythmia that results in a high risk of cerebral and peripheral embolism. Factor V Leiden and factor II G20210A variant are two leading conditions for venous thrombosis. The aim of our study was to find out whether these two common prothrombotic mutations play a role in the occurrence of embolic events in AF patients. We investigated 336 non-valvular AF patients and 336 healthy control subjects. Factor II G20210A variant was found in 24/336 patients (7.14%) and in 11/336 of control subjects (3.3%). At a multivariate analysis, factor II G20210A variant was independently associated to AF (OR 2.4 95% CI 1.1-5.2; p<0.05). No significant difference was observed in the prevalence of factor V Leiden in the two groups investigated [6/304 (2.0%) in patients vs 13/336 (3.9%) in controls (p=0.24)]. AF patients were separately analyzed in relation to the occurrence or absence of a cerebral or peripheral embolic event (200 with and 136 without embolic event). The prevalence of the two mutations among AF patients with and without an embolic event was similar [factor II G20210A polymorphism (7% and 7.3% respectively) and factor V Leiden (1.2% and 2.9%, respectively)]. No differences were found in relation to the type of embolic event. Our results suggest a possible relationship between the presence of prothrombin gene variant and AF per se.

Genetic determinants of fasting and post-methionine hyperhomocysteinemia in patients with retinal vein occlusion.

INTRODUCTION: Moderate hyperhomocysteinemia is considered a risk factor for both venous and arterial thrombosis. A prevalence of up to 30% of fasting hyperhomocysteinemia has been recently reported in patients with retinal vein occlusion (RVO) whereas conflicting data exist on the role of C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene as a risk factor for RVO. No report has been published on cystathionine beta-synthase (CBS) 844ins68 polymorphism (another genetic determinant of blood Hcy levels) in RVO patients. Moreover, scarce information is available on the usefulness of measuring homocysteine also after methionine loading to increase the diagnostic efficacy of hyperhomocysteinemia in RVO patients. MATERIALS AND METHODS: In 55 consecutive patients with diagnosis of RVO and 65 matched controls, plasma fasting total homocysteine (Hcy) levels and CBS and MTHFR polymorphisms were evaluated. In patients with normal fasting Hcy levels, post-methionine Hcy levels were determined. RESULTS: Moderate fasting hyperhomocysteinemia was detected in 18/55 patients (32.7%). In the remaining 37 patients, Hcy was measured again post-methionine loading (PML). Only 3/37 (8.1%) patients had PML hyperhomocysteinemia. Thus, the total prevalence of moderate hyperhomocysteinemia in this cohort of RVO patients was 21/55 (38.2%). The prevalence of homozygosity for C677T MTHFR genotype, but not that of heterozygosity for CBS844ins68, was significantly higher in RVO patients than in controls. CONCLUSIONS: Differently from what has been reported for arterial and/or venous thrombosis, a single fasting Hcy measurement is able to detect most of RVO patients (85.7%) with moderate hyperhomocysteinemia. C677T MTHFR, but not CBS 844ins68, genotype may play a role as risk factor for RVO.

Clotting activation after oral anticoagulant therapy discontinuation: a risk factor for recurrent venous thromboembolism.

A hypercoagulable state has been reported in some patients treated for venous thromboembolism (VTE) after oral anticoagulant treatment (OAT) discontinuation. It is unclear whether this is a risk factor for thrombosis recurrence. We investigated 139 patients with VTE and followed them up for a median of 20.5 months (6-90 months) to evaluate whether fragment 1 + 2 (F1 + 2) plasma levels are prognostic for VTE recurrence and to confirm clotting activation after OAT withdrawal. Fourteen patients had recurrences during the follow-up. F1 + 2 was measured the day before OAT withdrawal (T0) and 4 weeks later (T1) and its levels were similar in patients with spontaneous VTE versus those with transient risk factors for VTE. F1 + 2 levels increased from T0 to T1 (P < 0.0005). At T1, F1 + 2 values were significantly higher in patients with recurrence than in those without (P < 0.005). The negative predictive value of normal levels of F1 + 2 at T1 was 95%. In carriers of thrombophilic conditions no correlation was found between F1 + 2 levels and VTE recurrence. The results of this study confirm clotting activation after OAT discontinuation and suggest that higher F1 + 2 plasma levels are an independent risk factor for VTE recurrence.

Body mass index, gender, and clinical outcome among hypertensive and diabetic patients with stage A/B heart failure.

OBJECTIVE: The existence of an "obesity paradox" in asymptomatic patients with preclinical heart failure (HF) has not been investigated. The prognostic value of BMI in a cohort of hypertensive and diabetic patients with stage A/B HF enrolled in the PROBE-HF study was explored. DESIGN AND METHODS: BMI was measured in 1003 asymptomatic subjects (age 66.4 ± 7.8 years, 48% males) with hypertension and/or type 2 diabetes and no clinical evidence of HF. Predefined endpoints were all-cause mortality and a composite of death and hospitalization for cardiac causes. RESULTS: During a follow-up of 38.5 ± 4.1 months, 33 deaths were observed. Mortality in the normal BMI group (1.6 deaths per 100 patient-years) did not differ to that in the overweight group (1.1 per 100 patient-years, p = 0.31), but was higher than that in the obese group (0.4 per 100 patient-years, p = 0.0089). In multivariable analysis, obesity (hazard ratio [HR] 0.27 [0.09-0.85], p = 0.025) but not overweight (HR 0.68 [0.32-1.45], p = 0.32) was associated with lower risk of death. Obesity was also independently associated with reduced risk of the composite endpoint (HR 0.54 [0.28-0.99], p = 0.047). CONCLUSION: In asymptomatic hypertensive and diabetic patients with preclinical HF, obesity is associated with better survival and reduced risk of events.

Peripartum cardiomyopathy presenting with predominant left ventricular diastolic dysfunction: efficacy of bromocriptine.

Management of patients with peripartum cardiomyopathy (PPCM) is still a major clinical problem, as only half of them or slightly more show complete recovery of left ventricular (LV) function despite conventional evidence-based treatment for heart failure. Recent observations suggested that bromocriptine might favor recovery of LV systolic function in patients with PPCM. However, no evidence exists regarding its effect on LV diastolic dysfunction, which is commonly observed in these patients. Tissue Doppler (TD) is an echocardiographic technique that provides unique information on LV diastolic performance. We report the case of a 37-year-old white woman with heart failure (NYHA class II), moderate LV systolic dysfunction (ejection fraction 35%), and severe LV diastolic dysfunction secondary to PPCM, who showed no improvement after 2 weeks of treatment with ramipril, bisoprolol, and furosemide. At 6-week followup after addition of bromocriptine, despite persistence of LV systolic dysfunction, normalization of LV diastolic function was shown by TD, together with improvement in functional status (NYHA I). At 18-month followup, the improvement in LV diastolic function was maintained, and normalization of systolic function was observed. This paper might support the clinical utility of bromocriptine in patients with PPCM by suggesting a potential benefit on LV diastolic dysfunction.

Isolated papillary muscle rupture complicating acute pancreatitis.

Papillary muscle rupture in the absence of coronary stenoses is a rare event. An isolated infarction of the papillary muscle is involved in most cases, but the pathogenesis is still debated. We describe an anterolateral papillary muscle rupture complicating acute pancreatitis in a patient without significant coronary stenoses and with evidence of coronary spasm. This suggests that an increased susceptibility to coronary spasm and thrombosis, triggered by an acute systemic inflammatory response, may represent a mechanism of selective papillary muscle infarction.

A Educaçäo física, a formaçäo do cidadäo e os parâmetros curriculares nacionais / Physical education, sitizenship building and the national curriculum parameters

O Ministério da Educaçäo e do Desporto, através da Secretaria de Ensino Fundamental, inspirado no modelo educacional espanhol, mobilizou um grupo de pesquisadores e professores no sentido de elaborarem os Parâmetros Curriculares Nacionais (PCNs). Os PCNs têm como funçäo primordial subsidiar a elaboraçäo ou a versäo curricular dos estados e municípios. Neste estudo procurou-se analisar a proposta de Educaçäo Física para os 3 e 4 ciclos (5a a 8a. séries do ensino fundamental) contida nos parâmetros curriculares, área Educaçäo Física, procurando desvelar os seus aspectos inovadores, bem como apresentar e discutir as críticas formuladas aos documentos, desde os seus pressupostos teóricos, processo de elaboraçäo e realizaçäo dos PCNs. A metodologia consistiu em uma pesquisa qualitativa, através de análise bibliográfica. Os PCNs - área de Educaçäo Física para o 3o e 4o ciclos, apresentam alguns avanços e possibilidades importantes para o componente curricular...