Relationship between cardiac adrenergic image and exercise testing in heart failure

Messias, Leandro Rocha; Carreira, Maria Ângela M. de Queiroz; Miranda, Sandra Marina Ribeiro de; Azevedo, Jader Cunha de; Gava, Isabela Ambrósio; Rodrigues, Ronaldo Campos; Maróstica, Elizabeth; Nóbrega, Antônio Claudio Lucas da; Mesquita, Claudio Tinoco

doi:10.1590/S0066-782X2011005000044

Abstracts

BACKGROUND: The exercise treadmill test can be used in ventricular dysfunction patients for functional capacity or predicting prognosis. The cardiac image with 123I MIBG shows cardiac sympathetic activation. OBJECTIVE: To evaluate the relationship between exercise treadmill test variables and cardiac image changes in 123I MIBG. METHODS: 23 patients with LVEF < 45% performed scintigraphy cardiac with 123I MIBG and divided into two groups. G1: Washout rate < 27%; G2: > 27%. Systolic blood pressure (SBP), heart rate (HR) and functional capacity were evaluated. It was performed Student t test or Mann-Whitney U test, Spearman coefficient and linear regression. RESULTS: SBP at exercise peak (G1: 181.00 ± 28.01; G2: 153.27 ± 27.71 mmHg, p = 0.027), SBP variation [G1: 64(47.5-80.5); G2: 36(25-47) mmHg, p = 0.015], the HR at exercise peak (G1: 136.91 ± 19.66; G2: 118.45 ± 13.98 bpm, p = 0.018) and chronotropic response (G1: 70.42 ± 17.94; G2: 49.47 ± 14.89%, p = 0.006), and functional capacity [G1: 8.37(6.47-10.27); G2: 4.42(2.46-6.38) METs, p = 0.003] were smaller in G2 group. There was negative correlation between Washout rate and SBP at exercise peak (r = -0.505, p = 0.014), variation in SBP (r = -0.493, p = 0.017) and functional capacity (r = -0.646, p = 0.001). Nevertheless, SBP at exercise peak (r = -0.422, p = 0.016) and functional capacity (r = -0.804, p = 0.004) were the only variables associated with Washout rate, after linear regression. CONCLUSION: In heart failure patients, the SBP at exercise peak and functional capacity were the variables associated with Washout rate.

MIBG; exercise test; heart failure

FUNDAMENTO: Na insuficiência cardíaca, o teste ergométrico (TE) avalia capacidade funcional, um determinante de prognóstico. A cintilografia com I¹²³ MIBG mostra a ativação simpática cardíaca. OBJETIVO: Avaliar a associação entre as variáveis do TE e as alterações da cintilografia com I¹²³ MIBG. MÉTODOS: Foram submetidos 23 pacientes (FEVE < 45%) à cintilografia com I¹²³ MIBG e separados em: G1) taxa de Washout < 27%; G2) > 27%. Esses pacientes realizaram TE, onde foram analisadas: pressão arterial sistólica no pico do esforço (PASP), frequência cardíaca no pico do esforço (FCP), variação da pressão arterial sistólica intraesforço (Δ PAS), reserva cronotrópica e capacidade funcional em METs. Utilizaram-se para a análise estatística, o teste t de Student ou o teste U de Mann-Whitney, o coeficiente de Spearman e o coeficiente de regressão linear. RESULTADOS: A PASP (G1: 181,00 ± 28,01; G2: 153,27 ± 27,71, p = 0,027), a Δ PAS [G1: 64 (47,5-80,5); G2: 36 (25-47) mmHg, p = 0,015], a FCP (G1: 136,91 ± 19,66; G2: 118,45 ± 13,98 bpm, p = 0,018), a reserva cronotrópica (G1: 70,42 ± 17,94; G2: 49,47 ± 14,89%, p = 0,006) e a capacidade funcional [G1: 8,37 (6,47-10,27); G2: 4,42 (2,46-6,38) METs, p = 0,003] foram menores no G2. Houve correlação negativa entre taxa de Washout com PASP (r = -0,505, p = 0,014), Δ PAS (r = -0,493, p = 0,017) e capacidade funcional (r = -0,646, p = 0,001). Após regressão linear, PASP (r = -0,422, p = 0,016) e capacidade funcional (r = -0,804, p = 0,004) foram associadas com taxa de Washout. CONCLUSÃO: Em pacientes com insuficiência cardíaca, PASP e capacidade funcional foram as varáveis mais associadas com a taxa de Washout.

MIBG; teste de esforço; insuficiência cardíaca

FUNDAMENTOS: En la Insuficiencia Cardíaca, la Ergometría (Test Ergométrico - TE) evalúa la capacidad funcional, un determinante de pronóstico. El centellograma con I¹²³ MIBG muestra la activación simpática cardíaca. OBJETIVO: Evaluar la asociación entre las variables del TE y las alteraciones del centellograma con I¹²³ MIBG. MÉTODOS: Se sometieron 23 pacientes (FEVI < 45%) a centellograma con I¹²³ MIBG y se separaron en: G1) tasa de Washout < 27%; G2) > 27%. Estos pacientes realizaron TE, en el que se analizaron: presión arterial sistólica en el pico del esfuerzo (PAS P), frecuencia cardíaca en el pico del esfuerzo (FCP), variación de la presión arterial sistólica intraesfuerzo (Δ PAS), reserva cronotrópica y capacidad funcional en MET. Para el análisis estadístico se utilizaron el test t de Student o el test U de Mann-Whitney, el coeficiente de Spearman y el coeficiente de regresión lineal. RESULTADOS: La PAS P (G1: 181,00 ± 28,01; G2: 153,27 ± 27,71, p = 0,027), la Δ PAS [G1: 64 (47,5-80,5); G2: 36 (25-47) mmHg, p = 0,015], la FCP (G1: 136,91 ± 19,66; G2: 118,45 ± 13,98 lpm, p = 0,018), la reserva cronotrópica (G1: 70,42 ± 17,94; G2: 49,47 ± 14,89%, p = 0,006) y la capacidad funcional [G1: 8,37 (6,47-10,27); G2: 4,42 (2,46-6,38) MET, p=0,003] fueron menores menores en el G2. Hubo una correlación negativa entre la tasa de Washout con PASP (r = -0,505, p = 0,014), Δ PAS (r = -0,493, p = 0,017) y capacidad funcional (r = -0,646, p = 0,001). Después de la regresión lineal, PASP (r = -0,422, p = 0,016) y capacidad funcional (r = -0,804, p = 0,004) se asociaron con la tasa de Washout. CONCLUSIÓN: En pacientes con insuficiencia cardíaca, la PASP y la capacidad funcional fueron las variables más asociadas con la tasa de Washout. (Arq Bras Cardiol 2011;96(5):370-376)

MIBG; prueba de esfuerzo; insuficiencia cardíaca

ORIGINAL ARTICLE

Relationship between cardiac adrenergic image and exercise testing in heart failure

Leandro Rocha Messias^I; Maria Ângela M. de Queiroz Carreira^I; Sandra Marina Ribeiro de Miranda^I; Jader Cunha de Azevedo^I,II; Isabela Ambrósio Gava^I; Ronaldo Campos Rodrigues^I; Elizabeth Maróstica^I; Antônio Claudio Lucas da Nóbrega^I,II; Claudio Tinoco Mesquita^I,II

^IUniversidade Federal Fluminense, Niterói, RJ

^IIHospital Procardíaco, Rio de Janeiro, RJ - Brazil

Mailing address

ABSTRACT

BACKGROUNDS: The exercise treadmill test can be used in ventricular dysfunction patients for functional capacity or predicting prognosis. The cardiac image with 123I MIBG shows cardiac sympathetic activation.

OBJECTIVE: To evaluate the relationship between exercise treadmill test variables and cardiac image changes in 123I MIBG.

METHODS: 23 patients with LVEF < 45% performed scintigraphy cardiac with 123I MIBG and divided into two groups. G1: Washout rate < 27%; G2: > 27%. Systolic blood pressure (SBP), heart rate (HR) and functional capacity were evaluated. It was performed Student t test or Mann-Whitney U test, Spearman coefficient and linear regression.

RESULTS: SBP at exercise peak (G1: 181.00 ± 28.01; G2: 153.27 ± 27.71 mmHg, p = 0.027), SBP variation [G1: 64(47.5-80.5); G2: 36(25-47) mmHg, p = 0.015], the HR at exercise peak (G1: 136.91 ± 19.66; G2: 118.45 ± 13.98 bpm, p = 0.018) and chronotropic response (G1: 70.42 ± 17.94; G2: 49.47 ± 14.89%, p = 0.006), and functional capacity [G1: 8.37(6.47-10.27); G2: 4.42(2.46-6.38) METs, p = 0.003] were smaller in G2 group. There was negative correlation between Washout rate and SBP at exercise peak (r = -0.505, p = 0.014), variation in SBP (r = -0.493, p = 0.017) and functional capacity (r = -0.646, p = 0.001). Nevertheless, SBP at exercise peak (r = -0.422, p = 0.016) and functional capacity (r = -0.804, p = 0.004) were the only variables associated with Washout rate, after linear regression.

CONCLUSION: In heart failure patients, the SBP at exercise peak and functional capacity were the variables associated with Washout rate.

Key words: MIBG, exercise test; heart failure.

Introduction

In heart failure (HF), exercise testing (ET) is used to evaluate functional capacity, symptoms and therapy¹. Some of the parameters used in ET are the behavior of systolic blood pressure (SBP) intrastress and chronotropic reserve, which are recognized predictors of prognosis^2-4. The adrenergic hyperactivity, a characteristic of HF, may lead to chronotropic incompetence, decrease in cardiac contractile response to catecholamines and decreased sympathetic reserve during exercise. An inadequate response in SBP and heart rate (HR) has been associated with a twofold risk of mortality and adverse cardiovascular events^2,5-7. Both for the population⁸, and in the population with HF^2,9, functional capacity is an important predictor of prognosis and is not related to measures of ventricular function at rest nor with left ventricular ejection fraction¹⁰.

The activity and cardiac sympathetic innervation can be evaluated by scintigraphy with metaiodobenzylguanidine labeled with iodine 123 (I¹²³ MIBG)^11-13. Studies have found^13-16 that an early image represents the integrity of presynaptic nerve terminals and the density of betarreceptors. The presynaptic neuronal imaging contributes to the late image, combining information of neural function including capture, storage and release of norepinephrine in the presynaptic vesicles. The washout rate is a parameter that evaluates the degree of sympathetic activity. HF patients may have: (1) reduced tracer imaging due to loss of sympathetic neurons and/or disorders in primary uptake of norepinephrine; and (2) increased washout rate, reflecting the spillover of noradrenaline to the blood stream^11,14,17-19. A washout rate smaller than 27% is a strong predictor descriptor of survival²⁰.

So far, there is no evidence that the adrenergic hyperactivation at rest is associated with hemodynamic changes during exercise, or if the ET variables are associated with the scintigraphy variables. Therefore, the purpose of this study is to assess whether conventional ET variables in HF can detect patients with sympathetic dysfunction in I¹²³ MIBG scintigraphy. These findings could allow the assessment of risk with a technique available in our area, selecting those patients most likely to present changes to scintigraphy.

Methods

We selected 23 consecutive patients treated at the HF outpatient clinic of Hospital Universitário Antônio Pedro, Universidade Federal Fluminense. The selected patients had heart failure and left ventricular ejection fraction smaller than or equal to 45% measured by echocardiography by Simpson's technique. The study excluded patients who had: atrial fibrillation, diabetic patients, patients with ventricular pacing device, endocrine disorders, Parkinson's disease, pregnant or breastfeeding women. No medication has been suspended for the study and all patients were treated with optimized doses of standard drugs for HF, including beta-blocker (carvedilol). Volunteers signed a consent form agreeing to be part of the project. The project was approved by the Research Ethics Committee of Hospital Universitário Antônio Pedro, under number 011/09.

Patients underwent symptom-limited ET (ErgoPC 13 software version 2.2) on a treadmill, brand Imbramed, properly calibrated to manufacturer's directions, in the ramp protocol. We evaluated the behavior of systolic blood pressure (SBP), intrastress heart rate (HR) and functional capacity. The blood pressure measurement was performed by the indirect method using mercury column sphygmomanometer, duly calibrated, measured in the left arm of patients in the standing position. Heart rate was measured through RR interval of eletrocardiogram (ECG) by the software. SBP and HR at peak exercise, SBP variation at peak exercise compared to rest (Δ PAS) and index of chronotropic reserve were evaluated using the formula: ("{[HR at peak exercise - resting HR / (220 - age) - resting HR] x 100}")⁴. Functional capacity was estimated by the software according to the workload achieved.

Patients underwent myocardial scintigraphy with I¹²³ MIBG to assess cardiac adrenergic innervation, through radiotracer, by studying the heart/mediastinum relationship (H/M) for early images (30 minutes) and late images (4 hours), besides calculation of the washout rate {[(H/M early - H/M late) / (H/M early)] x 100}¹¹. All scintigraphic examinations were performed at Serviço de Medicina Nuclear do Hospital Pró-Cardíaco do Rio de Janeiro in Anger type digital CT scintillation camera (Single Photon Emission Computed Tomography) brand Siemens, E-Cam dual detector model, with low energy collimator and high resolution.

Patients were divided into two groups according to the washout (WO) rate: Group 1 (G1), washout rate < 27% (normal); Group 2 (G2), washout rate > 27% (amended)²¹. For the statistical analysis, software SPSS version 15 was used. For the evaluation of qualitative variables, we used the chi-square test. To evaluate the quantitative variables we used the Student t test or Mann-Whitney U test, according to data distribution. We used the Spearman correlation coefficient to evaluate the correlation of the variables of exercise with the WO. We used stepwise linear regression to identify variables associated with sympathetic hypertonia evaluated by the washout rate. Statistical significance was considered when p < 0.05.

Results

Patient characteristics are shown in Table 1. There were no significant differences in age, sex, body mass index, etiology of HF, left ventricular ejection fraction, medications and dosage of carvedilol between groups.

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The groups were similar at rest. At peak exercise, there was a significant difference between G1 and G2, but the latter had lower absolute values of SBP and HR, smaller intrastress SBP variation, lower rate of chronotropic reserve and a lower functional capacity. The parameters of the exercise are shown in Table 2 and Figure 1 shows the differences in SBP during exercise.

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Though divided by the washout rate, there was no significant difference in the early C/M ratio of I¹²³ MIBG (G1: 1.78 ± 0.25 vs G2: 1.74 ± 0.22, p = 0.710) and in late H/M ratio (G1: 1,74 ± 0,20 vs G2: 1,60 ± 0,22; p = 0.129). Figure 2 illustrates the cardiac imaging with I¹²³ MIBG in a patient with HF presenting normal HF parameters (functional capacity of 8.23 METs, intrastress SBP variation of 65 mmHg and chronotropic reserve index of 68%). The MIBG imaging was normal and the washout rate was 21%.

When we analyzed the correlation between exercise variables and the washout rate, we observed a significant negative correlation between the washout rate and the following variables: SBP at peak exercise, intrastress SBP variation and functional capacity (Table 3). No statistical significance was found in correlation with HR at peak exercise and chronotropic reserve index with WO (Table 3).

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After stepwise linear regression, the variables associated with dysautonomia by the washout rate were: SBP at peak exercise (r = -0.422; p = 0.016) and functional capacity in METs (r = -0.804; p = 0.004).

Discussion

In our study, we found that in patients with HF, SBP at peak exercise and functional capacity, measured by the number of METs achieved, are associated with changes in cardiac adrenergic innervation, as evidenced by the washout rate obtained by myocardial scintigraphy with I¹²³ MIBG. During ET, in patients with altered washout rate (state of adrenergic hypertonia at rest), we found that SBP at peak exercise and the number of METs showed lower values when compared with patients with normal washout rate. So far, there are no descriptions in literature of the association between such abnormal behavior in SBP and changes in cardiac adrenergic innervation by I¹²³ MIBG.

The variation in SBP during exercise is directly associatedwith cardiac output during exercise: a lower increase in intrastress SBP may result from inotropic deficit during the exercise, which is a common phenomenon in patients with ventricular dysfunction, and this finding is associated with a worse prognosis². Fargard et al²² in a sample of patients eligible for heart transplantation, demonstrated that an inadequate variation in SBP in response to submaximal exercise is a predictor of cardiac events.

Willians et al²³ evaluated patients with HF of different functional classes, demonstrating that simple parameters from the test, such as the duration and peak exercise SBP, are strong predictors of prognosis through multivariate analysis, exceeding the left ventricular ejection fraction and N-terminal proBNP ejection fraction (NT-proBNP).

Nishiyama et al² evaluated the blood pressure response during exercise as a predictor of prognosis in patients with HF. Through univariate analysis, SBP and HR at peak exercise, and their variations during exercise (ΔSBP/ΔHR = peak exercise - rest) were predictors of mortality. In this study, the group not surviving presented significantly lower values of these variables. After multivariate analysis, the Δ SBP and functional capacity, obtained through the number of METs achieved, were the best predictors of mortality, regardless of the use of beta-blockers.

Maximal oxygen consumption (VO₂) is a parameter used to assess, in patients with heart failure, eligible to cardiac transplantation²⁴, and is also a powerful predictor of prognosis^24-26. Willens et al²⁷ studying 40 patients with HF, functional class II and III of the New York Heart Association (NYHA), have shown that VO₂ max, both by indirect measurement (according to the time of the year), and by direct measurement, through the Cardiopulmonary Exercise Testing, is an important predictor of survival, providing useful information for monitoring patients. Another way to assess VO₂max by indirect measurement is by the number of METs achieved on the NT².

In a study involving healthy individuals Snader et al⁸ demonstrated that functional capacity was a powerful predictor of cardiovascular mortality. In this study, the rate of cardiovascular mortality was higher in the group that failed to reach 06 METs on ET, and its association with perfusion defects diagnosed by thallium scintigraphy, put these patients at a risk level even higher for adverse events.

Jeng et al²⁸ evaluated the influence of exercise tolerance on the quality of life in patients with HF. Patients who had a functional capacity greater than or equal to 05 METs, or a time of ET greater than or equal to 180 seconds, had a better quality of life, showing that the ET is safe, affordable and effective to assess exercise tolerance in this population. Rubim et al²⁹ showed that the number of METs achieved in ET correlated significantly with mortality.

Myers et al³⁰, evaluating quality of life scores, 06-minute walking test and number of METs achieved on ET in patients with HF, and correlating these variables with VO₂ max obtained through cardiopulmonary exercise testing, concluded that both reflect the patient's clinical status and have their importance in this clinical context, without, however, substituting one another. When compared to the distance covered in the 06-minute walking test, the functional capacity determined by the number of METs in ET correlated significantly better with the VO₂ max obtained through direct measurement.

Chandrashekhar et al³¹ analyzed the capacity of variables commonly used in ET in predicting VO₂ max. After stepwise regression analysis, the best predictor of VO₂ max was the number of METs achieved. Although the authors assert that the number of METs do not have a high precision, it still is a better predictor than the other clinical variables obtained, such as the HR behavior during exercise.

One of the most significant changes in the treatment of heart failure was the introduction of beta blockers. Parikh et al³², in HF patients, NYHA functional class III and IV, evaluated the effect of the beta-blocker metoprolol on the number of METs achieved on ET and concluded that the optimization of beta-blocker improves exercise performance, measured both by exercising time, and by the number METs.

Some studies suggest that the improvement, which is not universally observed, may be partly due to improved endothelial function due to the use of beta-blockers associated with inhibitor of angiotensin-converting enzyme³³.

Another aspect of risk markers in HF is through the neuroimaging. I¹²³ MIBG scintigraphy has been validated as a marker of prognosis, according to a meta-analysis with 1,755 patients, published by Verbene et al¹⁹ who demonstrated that a reduction of the C/M ratio in late imaging or washout rate increase in myocardial scintigraphy I¹²³ MIBG is associated with a worse prognosis when compared with patients with normal parameters. In a recent publication, Jacobson et al³⁴ in a multicenter study with patients with functional class NYHA II and III and left ventricular ejection fraction smaller than 35%, showed that the adrenergic direct assessment of the heart by myocardial scintigraphy with I¹²³ MIBG, was predictive of increased cardiac mortality and arrhythmic events, regardless of known prognostic factors such as left ventricular ejection fraction, brain natriuretic peptide levels and NYHA functional class.

Analyzing the functional information obtained by the neuroimaging with Cardiopulmonary Exercise Test, Cohen-Solal et al¹⁴ correlated VO₂ max with I¹²³ MIBG uptake and several other variables (left ventricular ejection fraction, hemodynamic parameters such as cardiac index and pulmonary capillary wedge pressure). Observed a significant correlation between adrenergic scintigraphic findings in I¹²³ MIBG and VO₂ max in the exercise. Analyzing their outcomes (cardiovascular death and heart transplantation), the major determinant of prognosis was VO₂ max. VO₂ max correlated better with the C/M ratio for late image than with the C/M to ratio for early image and the washout rate. In contrast, our study found a higher correlation with the washout rate with the number of METs achieved, rather than with late C/M ratio as in the study by Cohen-Solal et al¹⁴.

However, there are significant differences between the studies: In our study, we assessed VO₂ max by indirect measurement through the number of METs achieved, while Cohen-Solal et al¹⁴ have used a direct measurement of the VO₂. In the study by Cohen-Solal et al, only 13.0% of patients were taking beta-blockers, while in our study, all patients were using this medication. One of the actions of beta blockers is resensibilizing betareceptors, which may influence the C/M ratio, which could explain the differences between findings^5,35.

Study limitations

The main limitation in this study was the small number of patients. However, through a pilot study with 16 patients, a sample calculation was performed and the number of 23 patients has a statistical power of 90% to identify 50% difference in functional capacity and a statistical power of 80% to identify 50% of difference in SBP at peak exercise.

Another significant limitation is that we have employed the functional capacity by the number of METs achieved, rather than the VO₂ max calculated directly through cardiopulmonary exercise testing, because we did not have the necessary equipment at our institution at the time of this study. However, as the ET is a simple tool widely present in our environment, we believe that the information derived from this examination may be useful for cardiologists involved in clinical practice of patients with HF, since it is correlated with the sophisticated analysis of cardiac innervation. Another important variable observed as significant in our study was that SBP at peak exercise, is also derived from ET and does not require complex methodologies for analysis.

Conclusion

Patients with HF and washout rate changed in I¹²³ MIBG myocardial scintigraphy showed a lower inotropic and chronotropic response, and a lower functional capacity. SBP at peak exercise and the number of METs were the ET variables most associated with this adrenergic hypertonia assessed by scintigraphy. Conventional ET, through the evaluation of these two variables, can be used as a way to predict the presence of adrenergic hyperactivity in patients with heart failure.

Acknowledge

Acknowledge to FAPERJ and CNPq for the support given to research projects conducted by Universidade Federal Fluminense.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Sources of Funding

There were no external funding sources for this study.

Study Association

This article is part of the thesis of master submitted by Leandro Rocha Messias, from Universidade Federal Fluminense.

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28. Jeng C, Yang MH, Chen PL, Ho CH. The influence of exercise tolerance on quality of life among patients with heart failure. Qual Life Res. 2004;13(5):925-32.
29. Rubim VS, Drumond Neto C, Romeo JL, Montera MW. Valor prognóstico do teste de caminhada de seis minutos na insuficiência cardíaca. Arq Bras Cardiol. 2006;86(2):120-5.
30. Myers J, Zaheer N, Quaglietti S, Madhavan R, Froelicher V, Heidenreich P. Association of functional and health status measures in heart failure. J Card Fail. 2006;12(6):439-45.
31. Chandrashekhar Y, Anand IS. Can common exercise indices determine peak exercise oxygen consumption and anaerobic threshold during stress testing in patients with chronic congestive heart failure? Indian Heart J. 1993;45(6):493-5.
32. Parikh KH, Hetal A, Milan C, Urmil G, Hemang A, Anish C, Ajay M, et al. Effect of Metoprolol CR/XL on pulmonary artery pressure in chronic heart failure patients assessed by an implanted ultrasonic device with special emphasis on diurnal variation and exercise capacity. Indian Heart J. 2009;61(1):34-9.
33. Poelzl G, Frick M, Lackner B, Huegel H, Alber HF, Mair J, et al. Short-term improvement in submaximal exercise capacity by optimized therapy with ACE inhibitors and beta blockers in heart failure patients is associated with restoration of peripheral endothelial function. Int J Cardiol. 2006;108(1):48-54.
34. Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, et al. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure: results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010;55(20):2212-21.
35. Kasama S, Toyama T, Hatori T, Sumino H, Kumakura H, Takayama Y, et al. Evaluation of cardiac sympathetic nerve activity and left ventricular remodelling in patients with dilated cardiomyopathy on the treatment containing carvedilol. Eur Heart J. 2007;28(8):989-95.

Correspondência:

Leandro Rocha Messias

Rua Noronha Torrezão, 46 / 805 - Santa Rosa

24240-182 - Niterói, RJ - Brasil

E-mail:

lmessias@cardiol.br,

leandromess@gmail.com

Publication Dates

Publication in this collection
15 Apr 2011
Date of issue
May 2011

History

Reviewed
09 Nov 2010
Received
22 Aug 2010
Accepted
20 Dec 2010

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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[29] 29. Rubim VS, Drumond Neto C, Romeo JL, Montera MW. Valor prognóstico do teste de caminhada de seis minutos na insuficiência cardíaca. Arq Bras Cardiol. 2006;86(2):120-5.

[30] 30. Myers J, Zaheer N, Quaglietti S, Madhavan R, Froelicher V, Heidenreich P. Association of functional and health status measures in heart failure. J Card Fail. 2006;12(6):439-45.

[31] 31. Chandrashekhar Y, Anand IS. Can common exercise indices determine peak exercise oxygen consumption and anaerobic threshold during stress testing in patients with chronic congestive heart failure? Indian Heart J. 1993;45(6):493-5.

[32] 32. Parikh KH, Hetal A, Milan C, Urmil G, Hemang A, Anish C, Ajay M, et al. Effect of Metoprolol CR/XL on pulmonary artery pressure in chronic heart failure patients assessed by an implanted ultrasonic device with special emphasis on diurnal variation and exercise capacity. Indian Heart J. 2009;61(1):34-9.

[33] 33. Poelzl G, Frick M, Lackner B, Huegel H, Alber HF, Mair J, et al. Short-term improvement in submaximal exercise capacity by optimized therapy with ACE inhibitors and beta blockers in heart failure patients is associated with restoration of peripheral endothelial function. Int J Cardiol. 2006;108(1):48-54.

[34] 34. Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, et al. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure: results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010;55(20):2212-21.

[35] 35. Kasama S, Toyama T, Hatori T, Sumino H, Kumakura H, Takayama Y, et al. Evaluation of cardiac sympathetic nerve activity and left ventricular remodelling in patients with dilated cardiomyopathy on the treatment containing carvedilol. Eur Heart J. 2007;28(8):989-95.