Causes of cardiovascular and noncardiovascular death in the ISCHEMIA trial.

BACKGROUND: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported. METHODS: We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as CV, non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death. RESULTS: Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies (2.6% vs 3.0%; hazard ratio [HR] 0.98; 95% CI [0.70-1.38]), but non-CV death rates were higher in the invasive strategy (3.3% vs 2.1%; HR 1.45 [1.00-2.09]). Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths (0.6% vs 1.3%; HR 0.48 [0.24-0.95]) and more malignancy deaths (2.0% vs 0.8%; HR 2.11 [1.23-3.60]) occurred in the invasive strategy than in the conservative strategy. CONCLUSIONS: In International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results.

Clinical outcomes vary between the Shuttle Walk Test and Stress Test in patients with coronary artery disease.

Purpose: The purpose of this study was to determine if the Incremental Shuttle Walk Test (ISWT) can elicit similar patient responses as a treadmill stress test in patients with coronary artery disease (CAD). Methods: Both the stress test and the ISWT were performed by 172 participants, aged 60.67±10.23 years. We screened participants for unstable angina, severe aortic stenosis, uncontrolled hypertension, and excluded if unable to walk on a treadmill. Outcome measures (signs and symptoms) included: i) patient-reported chest pain; ii) patient-reported breathlessness/exhaustion and not being able to keep up with test protocol; and iii) able to reach target HRmax. Additionally, EKG changes during the stress test were monitored for ST changes or arrhythmias. Results: During the stress test, 15 participants reported chest pain, 23 participants reached target HRmax. No participants reported chest pain and 2 participants reached target HRmax during the ISWT. Participants reporting chest pain had a higher mean BMI and significant difference in METS (p < 0.001) during the stress test and walking distance (p = 0.03) when compared with patients who did not report chest pain during the stress test. Breathlessness and not being able to keep up with protocol were the most commonly reported in both tests. Changes in EKG were observed in 38 participants in the stress test. Conclusion: A maximal effort stress test is better at eliciting ischemic signs and symptoms and a superior tool for diagnosis of progression or severity of CAD than the ISWT. Appropriate selection of exercise tests is important in the clinical setting.

The use of multisite left ventricular pacing via quadripolar lead improves acute haemodynamics and mechanical dyssynchrony assessed by radial strain speckle tracking: initial results.

AIMS: The objective of the present study was to evaluate the effect of multipoint pacing (MPP) on acute haemodynamics, cardiac contractility, and left ventricle (LV) dyssynchrony, in comparison with conventional cardiac resynchronization therapy (CRT). METHODS AND RESULTS: An open-label, non-randomized, single-centre, prospective study was designed. Twenty-seven consecutive patients were included. Evaluation of pacing configurations was performed in a random order. Transthoracic echocardiography was used to obtain haemodynamic and dyssynchrony parameters. Left ventricular ejection fraction (LVEF) was significantly superior in MPP compared with baseline (38.4 ± 1.8% vs. 26.1 ± 2.2%; P < 0.001), and in conventional pacing configuration compared with baseline (33.2 ± 1.8% vs. 26.1 ± 2.2%; P = 0.007). Cardiac index (CI) was increased by 21.8 ± 5.4% and 34.7 ± 5.1% in conventional and MPP configurations, respectively (P = 0.19). Percentage of acute responders (CI increase ≥10%) was 62.9 and 85.2% in conventional and MPP, respectively (P < 0.001). LV dyssynchrony was defined by radial strain rate parameters. Baseline anteroseptal-to-posterior wall time delay was 168 ± 21 ms. It was reduced until 70.4 ± 29 ms in conventional and -6.6 ± 11 ms in MPP (conventional vs. baseline P = 0.04; MPP vs. conventional P = 0.05). Standard deviation of the time-to-peak radial strain of the 6 LV basal segments was 101 ± 9.7, 80.3 ± 9.2, and 66 ± 8.03 ms in baseline, conventional, and MPP configurations, respectively (MPP vs. basal P = 0.012). Finally, we observed a positive correlation (r = 0.69) between reduction in dyssynchrony and CI increase (P < 0.0001). CONCLUSION: MPP showed a further reduction in LV dyssynchrony compared with conventional biventricular pacing. Moreover, MPP resulted in an additional improvement in LVEF and in CI, and this was translated into a higher number of acute responders to CRT.

[Long-term prognosis of serum and urine n-terminal proBNP levels and glomerular filtration rate in heart failure patients]. / Valor pronóstico a largo plazo de los valores séricos y urinarios del fragmento N-terminal del péptido natriurético tipo B y del filtrado glomerular en pacientes con insuficiencia cardíaca.

BACKGROUND AND OBJECTIVE: The amino-terminal pro-brain natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) values are related to short prognosis in patients with heart failure (HF). This study evaluates the prognostic power of serum and urinary NT-proBNP levels, and eGFR values, in HF patients during a 60-month follow-up. PATIENTS AND METHODS: We studied 93 HF outpatients (66 males, age 65+/-12). Primary endpoint was defined as cardiovascular mortality and secondary endpoint as cardiovascular mortality or admissions. RESULTS: Only serum NT-proBNP levels had a significant area under the curve for the prognosis of 60-month mortality and combined events, 0.70 (p=0.004) and 0.67 (p=0.019), respectively. Urinary NT-proBNP and eGFR did not have statistical significant areas under the curve. Patients with high serum NT-proBNP had the highest risk of cardiovascular death [44 (IC 95% 38-50) vs. 56 (IC 95% 53-59) months, p=0.0006] and combined events [33 (IC 95% 28-38) vs. 42 (IC 95% 28-38) months; p=0.027]. After the integration of serum NT-proBNP and renal function, patients with high peptide levels and low eGFR had the worst survival [42 (IC 95% 33-52) months; p=0.010]. Finally, only serum NT-proBNP concentration above 933 pg/mL was a predictor of poor survival (hazard ratio=2.81, p=0.033) and NT-proBNP above 550 pg/mL for combined events (hazard ratio=1.79, p=0.049). CONCLUSIONS: Serum NT-proBNP levels were superior to urine NT-proBNP and eGFR values for predicting 60-month cardiovascular death and combined events in HF patients.

Urinary NT-proBNP. A valuable marker in the assessment of patients with essential hypertension.

The aim was to evaluate the usefulness of urinary N-terminal fragment of B-type natriuretic peptide (NT-proBNP) measurement for predicting the presence of left ventricular hypertrophy (LVH) in 160 asymptomatic patients with essential hypertension. The urinary NT-proBNP/creatinine ratio was higher in patients with LVH than in either those without LVH (P< .0001) or control subjects (P< .0001). Multivariate linear regression analysis identified age (P=.034), left ventricular mass index (P=.026) and serum NT-proBNP level (P=.001) as predictors of the urinary peptide level. The area under the curve for the NT-proBNP/creatinine ratio was 0.71+/-0.04 (P< .0001) for identifying LVH. Logistic regression analysis showed that the NT-proBNP: creatinine ratio was a predictor of LVH (odds ratio=4.074; P=.009). In conclusion, the urinary NT-proBNP concentration is a new marker that could be useful for identifying LVH in subjects with essential hypertension.

[Prognostic value of big endothelin-1 prognostic value in patients with heart failure and moderately symptomatic functional class]. / Valor pronóstico de big endotelina-1 en pacientes con insuficiencia cardíaca y clase funcional moderadamente sintomática.

BACKGROUND AND OBJECTIVE: Several studies have analyzed big endothelin-1 as a marker of mortality in patients with severe heart failure (HF). However, it has not proven prognostic value in patients with moderately symptomatic functional class. Our objective was to evaluate, in a 24 months follow-up, the prognostic power of big endothelin-1 in patients with HF and moderately deteriorated functional class. MATERIAL AND METHOD: Big endothelin-1 levels were measured in a cohort of 90 outpatients (age 64 (13), 70% males) diagnosed with HF. Patients were functionally classified (NYHA). RESULTS: For the whole population, big endothelin-1 was 0.86 (0.61-1.20)fmol/ml. We evaluated its predictive value in detecting cardiovascular mortality, obtaining an AUC of 0.68 (0.08) (P=.02), and a cut-off value of 0.98 fmol/ml (sensitivity 69%, specificity 75%). When a logistic regression analysis was performed, big endothelin-1 was also an independent predictor of mortality (OR=5.851, P=.009). CONCLUSIONS: Big endothelin-1 predicts cardiovascular mortality in patients diagnosed of HF and moderately symptomatic functional class.

[Urinary NT-proBNP level: relationship with ventricular function parameters in heart failure]. / NT-proBNP en orina y su relación con los parámetros de la función ventricular en la insuficiencia cardiaca.

INTRODUCTION AND OBJECTIVES: The plasma N-terminal probrain natriuretic peptide (NT-proBNP) level is a sensitive marker of ventricular dysfunction. The diagnostic and prognostic value of urinary NT-proBNP measurement has been demonstrated. The objective of this study was to determine the relationship between established parameters of ventricular function and the urinary NT-proBNP level. METHODS: The study involved 74 patients with heart failure (54 male, age 66 [12] years). A Doppler echocardiographic study was performed to measure atrioventricular plane displacement (AVPD), ejection fraction, mitral flow propagation velocity, and E/A. Urinary and plasma NT-proBNP levels, and the plasma aldosterone level were measured. RESULTS: In the whole group, the plasma NT-proBNP level was 948 (961) pg/mL, the urinary NT-proBNP level was 88.7 (17.8) pg/mL, and the aldosterone level, 165 (145) pg/mL. There were correlations between urinary NT-proBNP level and AVPD (r=-0.5; P< .0001), ejection fraction (r=-0.3; P< .01), and mitral flow propagation velocity (r=-0.24; P< .05). On dividing AVPD and ejection fraction measurements into quartiles, respectively, the urinary NT-proBNP levels for these quartiles were Q1: 103 (28) pg/mL, Q2: 89 (9) pg/mL, Q3: 86 (9) pg/mL, and Q4: 78 (9) pg/mL (P< .0001) and Q1: 101 (26) pg/mL, Q2: 85 (12) pg/mL, Q3: 83 (10) pg/mL, and Q4: 85 (11) pg/mL (P< .05), respectively. Multiple linear regression analysis showed that the plasma NT-proBNP level was an independent predictor of the urinary NT-proBNP level (P< .0001). When the plasma NT-proBNP level was excluded, AVPD and ejection fraction appeared as alternative independent predictors (P< .05). CONCLUSIONS: There is a correlation between the urinary NT-proBNP level and left ventricular function parameters. This study supports the use of the urinary NT-proBNP level as a biochemical marker of ventricular function in heart failure patients.

[8-hydroxy-2'-deoxyguanosine and lipid peroxidation in patients with heart failure]. / Valores de 8-hidroxi-2'-desoxiguanosina y de peroxidación lipídica en pacientes con insuficiencia cardiaca.

INTRODUCTION AND OBJECTIVES: Heart failure is associated with increased free radical production, which leads to a state of oxidative stress. Known markers of oxidative stress include 8-hydroxy-2'-deoxyguanosine, which reflects oxidative damage to DNA, and lipid peroxidation, which can be used to quantify damage to lipid-rich structures. The aims of this study were to compare 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels in heart failure patients and healthy subjects and to assess how these levels are influenced by heart failure etiology. METHODS: The study included 78 patients (57 male, age 64 [14] years) with heart failure and 12 control subjects. Patients completed a questionnaire and were graded according to the New York Heart Association classification. Doppler echocardiography was performed and blood samples were obtained. 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels were determined. RESULTS: Significant differences were observed between patients and control subjects in 8-hydroxy-2'-deoxyguanosine and lipid peroxidation levels, at 0.34 (0.54) ng/mL vs 0.04 (0.07) ng/mL (P<.05), and 18 (10) microM vs 8 (3) microM (P<.01), respectively. Subsequent analysis showed that heart failure etiology had a significant effect on the levels of the two markers (P<.05), which were highest in patients with hypertensive cardiomyopathy. CONCLUSIONS: Levels of 8-hydroxy-2'-deoxyguanosine and lipid peroxidation were higher in heart failure patients than in control subjects. The most significant increases were found in patients with hypertensive cardiomyopathy.

Maximum longitudinal relaxation velocity of the left ventricle: its clinical value and relationship with NT-proBNP plasma levels in heart failure.

BACKGROUND: M-mode recordings of the mitral annulus to measure the maximum ascending velocity during early diastole as an expression of maximum longitudinal relaxation velocity of the left ventricle (RVm) can be used as an index of left ventricular (LV) diastolic function. The purpose of this study was to determine the relationship of RVm with LV functional parameters in patients with heart failure, with N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels, and with their functional classification. METHODS AND RESULTS: RVm was recorded in 97 patients by M-mode echocardiography. Patients were classified according to the New York Heart Association (NYHA) and the concentration of NT-proBNP was determined. Patients with ejection fraction (EF)>40 showed a significant correlation between RVm and mitral annulus motion (MAM), mitral flow propagation velocity, E/A, age, deceleration time (DT), and NT-proBNP. In patients with EF40, though its relationship with NT-proBNP both in patients with EF>or40 it is influenced only by age. RVm values showed a significant decrease in NYHA class II and III.

Left ventricular cavity area reflects N-terminal pro-brain natriuretic peptide plasma levels in heart failure.

AIMS: N-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in the diagnosis of heart failure (HF). LV two-dimensional cavity area from end-diastole (LVEDA) and end-systole (LVESA), and LV fractional area change (LVFAC) reflect changes in LV morphology and function without using geometric assumptions. In a multicenter study, we correlated LVEDA, LVESA and LVFAC with NT-proBNP, comparing patients with dilated and ischemic cardiomyopathy. METHODS AND RESULTS: We studied 106 HF patients. In the dilated group, NT-proBNP correlated with LVEDAI (r=0.6), LVESAI (r=0.7) and LVFAC (r=-0.6), all significant at p<0.001. In patients with ischemic cardiomyopathy we found LVESAI (r=0.3, p<0.05) and LVFAC (r=-0.4, p<0.01). After adjustment for age and BMI, LVFAC and LVESAI were associated in a multiple linear regression analysis with peptide levels (adjusted r(2)=0.5, p<0.001). CONCLUSIONS: In this study we found a good correlation of NT-proBNP with LV cavity areas and LVFAC. Multiple regression analysis showed that when adjusted for age and BMI, LVFAC and LVESAI are independent predictors of NT-proBNP levels in both dilated and ischemic etiologies. Patients with dilated cardiomyopathy showed better results than those with ischemic cardiomyopathy. We think LV areas are a useful and reproducible parameter, do not need geometric assumptions and reflect NT-proBNP plasma levels.

[Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients]. / Relación de los valores plasmáticos de big endotelina-1 con NT-proBNP y la función ventricular de pacientes con insuficiencia cardíaca.

INTRODUCTION AND OBJECTIVES: Elevated plasma concentrations of big endothelin-1 (big ET-1) are related with severity and prognosis in patients with heart failure, and N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of ventricular remodeling. The purpose of this study was to investigate the relationship between plasma levels of big ET-1 and NT-proBNP, and between the former and ventricular function. PATIENTS AND METHOD: We studied 103 patients with heart failure (75 men, mean age 63 [13] years). Each participant completed a questionnaire and underwent Doppler echocardiographic study to measure ejection fraction (EF), mitral flow propagation velocity (Vp) and atrioventricular plane displacement (AVPD). Blood samples were also taken to determine plasma levels of big ET-1, aldosterone and NT-proBNP. RESULTS: For the whole population big ET-1 concentration was 1.03 [0.75] fmol/m, NT-proBNP 619 (307-1328) pg/mL, aldosterone 168 [102] pg/mL, EF 37 [10], Vp 37 [11] cm/s, and AVPD 8.0 [1.7] mm. Plasma big ET-1 correlated positively with plasma NT-proBNP (r=0.50, P<.0001). However, a negative correlation was found between big ET-1 and EF (r=-0.30, P<.01), Vp, (r=-0.30, P<.01) and AVPD (r=-0.21, P<.05). When ET-1 levels were divided into quartiles and the corresponding NT-proBNP, EF, Vp and AVPD values were compared, we found significant differences (ANOVA P<.0001, P<.01, P<.05 and P<.05, respectively). CONCLUSIONS: Plasma levels of big ET-1 correlated positively with NT-proBNP levels and inversely with EF, Vp and AVPD. These findings help clarify the relationships between ventricular function and the neurohormonal activation involved in heart failure, and may aid the search for therapeutic interventions.

Ventricular hypertrophy increases NT-proBNP in subjects with and without hypertension.

BACKGROUND: It has been published that hypertension (HT) must be taken into account when using NT-proBNP, but left ventricular (LV) hypertrophy without HT could be a cause of NT-proBNP elevation. In a population study we compared NT-proBNP in subjects with hypertrophy, with and without diagnosis of HT. METHODS: We studied 215 subjects from a random sample of 432 people who had declared to suffer from dyspnea. These 432 subjects were referred to their hospital where blood samples were taken, an echo-Doppler study was performed and a specific questionnaire was completed. We got a positive answer from 215, and 52 (24%) have LV hypertrophy. RESULTS: When we compared NT-proBNP in non-hypertrophic population, 148 +/- 286 pg/ml, with NT-proBNP in LV hypertrophic population, 202 +/- 209 pg/ml, we found P < 0.001. In the hypertrophic group, when we compared NT-proBNP (199 +/- 201 pg/ml) in normotensive subjects (LV mass index 170 +/- 70 g/m2, Vp 50 +/- 18 cm/s, LVEF 62 +/- 8) with NT-proBNP (205 +/- 220 pg/ml) in subjects with diagnosis of HT (LV mass index 169 +/- 37 g/m2, Vp 55 +/- 20 cm/s, LVEF 64 +/- 10), we found NS. CONCLUSIONS: This population study shows that NT-proBNP is elevated in patients with LV hypertrophy with or without HT. In LV hypertrophy the presence of HT does not influence the peptide levels significantly.

[NT-proBNP levels and hypertension. Their importance in the diagnosis of heart failure]. / Hipertensión y valores de NT-proBNP. Su importancia en el diagnóstico de insuficiencia cardíaca.

INTRODUCTION: N-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in the diagnosis of heart failure. We compared NT-proBNP levels in patients with and without a diagnosis of arterial hypertension. PATIENTS AND METHOD: Participants were recruited from a random sample of 999 inhabitants from the Community of Valencia (eastern Spain). Of these patients, 432 said they suffered from dyspnea and were referred to their hospital (10 hospitals involved), where blood samples were taken, an echo-Doppler study was performed, and the patients completed a questionnaire. Of the 432 participants with dyspnea, 215 gave informed consent for their inclusion in the study, and 202 completed the study. Hypertension was diagnosed in 72 participants and 130 were normotensive. RESULTS: For the whole population, NT-proBNP, expressed as the median and range, was 88 (0-2586) pg/mL. When we compared hypertensive with normotensive participants, we found higher NT-proBNP levels in the former group: median 123, range 0-2184 pg/mL, versus median 77, range 0-2586 pg/mL (P<.01). When we excluded subjects with systolic left ventricular dysfunction, we found higher levels in participants with hypertension: 119 (0-2184 pg/mL) vs 72 (0-997 pg/mL) (P<.01). When we also excluded subjects with diastolic dysfunction, we found (median 85, range 0-430 pg/mL) and (median 66, range 0-997 pg/mL), respectively (p = NS). CONCLUSION: In a population study of subjects with dyspnea, hypertensive patients have higher NT-proBNP levels than subjects with normal blood pressure. This difference disappeared when patients with diastolic dysfunction were excluded from the analysis. Hypertension can thus be a confounding factor that potentially decreases the specificity of NT-proBNP levels for the diagnosis of heart failure. These findings should be taken into account when conducting clinical and epidemiological studies in which patients with both heart failure and hypertension are included.

[NT-proBNP and atrioventricular plane displacement. Relationship and diagnostic implications]. / NT-proBNP y desplazamiento del plano auriculoventricular. Relación e implicaciones diagnósticas.

INTRODUCTION AND OBJECTIVES: NT-proBNP is useful in the diagnosis of heart failure and ventricular dysfunction. Left atrioventricular plane displacement (AVPD) is a consolidated index of ventricular function. Our objective was to carry out a multicenter population-based study to establish the relationship between plasma NT-proBNP levels with AVPD values. PATIENTS AND METHOD: We studied 215 subjects (age 66 9 years; 57.7% women) chosen from a random sample of 432 people from the Community of Valencia, who previously reported suffering from some degree of dyspnea. Doppler echocardiography was done, AVPD was calculated and plasma NT-proBNP concentrations were determined. All studies were completed in 194 patients. RESULTS: For the whole population NT-proBNP was 88 (0-2,586) pg/ml and AVPD was 11.9 1.6 mm. NT-proBNP concentration correlated well with AVPD (r = 0.44; p < 0.00001), and higher peptide levels were obtained in AVPD quartiles that indicated less displacement (p < 0.05). When NT-proBNP values were grouped according to their association with AVPD lower or higher than the 50th percentile AVPD, the difference was significant at p < 0.01. When AVPD values lower and higher than 10 mm were compared, NT-proBNP values were higher in persons with AVPD lower than 10 mm (p < 0.05). CONCLUSIONS: This population study found higher NT-proBNP concentrations in subjects with lower AVPD, and illustrates the potential diagnostic usefulness of NT-proBNP in clinical practice.