Skip Navigation

European Journal of Heart Failure 2007 9(2):168-172; doi:10.1016/j.ejheart.2006.04.002
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Toutouzas, K.
Right arrow Articles by Stefanadis, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Toutouzas, K.
Right arrow Articles by Stefanadis, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2007 European Society of Cardiology

Coronary sinus thermography in idiopathic dilated cardiomyopathy: Correlation with systemic inflammation and left ventricular contractility

Konstantinos Toutouzas*, Pavlos Stougiannos, Maria Drakopoulou, John Mitropoulos, Eirini Bosinakou, Virginia Markou, George Latsios, Ioannis Karabelas, Elli Stefanadi and Christodoulos Stefanadis

First Department of Cardiology, Hippokration Hospital, Athens Medical School Athens, Greece

* Corresponding author. 24 Karaoli and Dimitriou, Holargos, Athens 15562, Greece. Tel.: +30 210 6510860; fax: +30 210 7784590. E-mail address: ktoutouz{at}otenet.gr


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Background: Previous studies have demonstrated that patients with heart failure have increased myocardial heat production. Coronary sinus (CS) thermography is a new method for the evaluation of left ventricular heat production.

Aims: We investigated whether the CS blood temperature is increased in patients with idiopathic dilated cardiomyopathy (DCM) compared to a control group and whether the CS blood temperature correlates with ejection fraction and systemic inflammatory activation.

Methods and results: We included 25 patients with DCM and 22 healthy subjects. Temperature measurements were performed using a new thermography catheter. Temperature difference ({Delta}T) was defined as the difference between the CS and RA blood temperature. The CRP levels were also measured.

{Delta}T was significantly greater in patients with DCM compared to the controls (0.25±0.09 vs 0.14±0.07 °C, p<0.01). {Delta}T and EF were inversely correlated in patients with DCM (R=0.43). We categorized patients with DCM into two groups using a CRP cut-off value of ≤1 mg/dL. {Delta}T in patients with high CRP was less (0.21±0.06 °C) compared to patients with low CRP (0.30±0.08 °C, p=0.01).

Conclusions: In patients with DCM increased heat production from the myocardium, as estimated from the coronary sinus blood temperature, was demonstrated, interestingly there was no correlation with systemic inflammatory activation.

Key Words: Dilated cardiomyopathy • Coronary sinus thermography • Heat production

Received August 5, 2005; Revised January 2, 2006; Accepted April 3, 2006


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Dilated cardiomyopathy (DCM) is a syndrome characterized by the enlargement of the cardiac chambers and impaired systolic function of one or both ventricles. It is likely that this condition represents a final common pathway that is the end-result of myocardial damage produced by a variety of cytotoxic, metabolic, immunological, familial and infectious mechanisms, including myocardial inflammation [1].

It has been shown in previous studies, that in heart failure a significant proportion of myocardial energy is transformed to heat instead of kinetic energy [2-4]. Thus, the blood in the coronary circulation, in addition to its nutritional role also serves as a "radiator" cooling the myocardial muscle. The majority of the venous return of the left ventricle, which is the main energy producing and consuming chamber of the heart, is delivered through the major cardiac vein to the coronary sinus (CS). The transfer of a proportion of the excess heat through the coronary circulation may result in increased CS blood temperature [5].

Another pathophysiological mechanism, which has not been extensively studied in patients with DCM, is systemic inflammatory activation [6]. In patients with acute coronary syndromes, an increased CS blood temperature compared to the right atrium temperature has been observed, mainly due to systemic inflammation. However, in patients with idiopathic DCM the inflammatory activation is doubtful, especially in symptomatic patients with end stage heart failure.

The purpose of our study was to investigate 1) whether there is increased CS blood temperature in patients with idiopathic DCM compared to a control group, 2) whether there is a correlation between the CS blood temperature with the mechanical performance of the left ventricle, evaluated by ejection fraction, 3) the role of systemic inflammatory activation in the CS temperature, evaluated from the C-reactive protein (CRP) levels.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusions
 References
 
2.1. Study population
The study group consisted of 47 consecutive subjects. Of these, 25 had idiopathic DCM (mean age 56.52±15.13 years), and underwent cardiac catheterization for the evaluation of congestive heart failure. The control group consisted of 22 subjects (mean age 62.95±10.65 years) without angiographically proven coronary artery disease or cardiac dysfunction, who underwent coronary angiography for evaluation of chest pain of recent onset.

All patients in the DCM group had symptoms of heart failure (NYHA class II-IV) for at least 6 months, no angiographically visible narrowing of the coronary arteries and an ejection fraction <40%. Patients with heart failure due to a specific aetiology (coronary artery disease, hypertension, valvular or congenital heart disease) were excluded from the study. Patients with a history of known viral infection possibly associated with symptom onset were also excluded. Five patients in the DCM group had well controlled stage 1 hypertension; hypertensive cardiomyopathy was excluded in these patients. None of the patients had symptoms or signs of infectious, autoimmune or inflammatory disease, malignancy, thyroid disease or was under treatment with corticosteroids or NSAIDS, except for aspirin. Left ventricular volumes and mass were measured in all patients according to previous studies [7]. Blood samples were obtained before the procedure for measuring CRP levels (Dade Behring, Marburg GmbH, Germany).

The study protocol was approved by the ethics committee of our institution and all participants gave written informed consent.

2.2. The thermography catheter
The thermographic catheter (7Fr) (Medispes Co., Switzerland), which was designed and developed in our institution, has been previously described [5]. A steering arm with a connector for the thermistor lead wires is attached to the proximal part of the catheter. The steering arm passes through the lumen of the catheter and is attached to its tip. The distal 7 cm of the catheter shaft consists of a soft non-thrombogenic material. The thermistor lead-wires end at the connector and pass through another lumen of the catheter. A thermistor probe [8] is positioned at the centre of the catheter tip. Manipulation of the steering arm proximally enables the distal end of the catheter to be curved (0° to180°). Data acquisition and processing have been previously described [5]. Briefly, the sensitivity of the thermistor is 0.05 °C and time-constant is 300 ms.

2.3. Study protocol
The participants were fasted and were not permitted to smoke for at least 12 h before the study procedure. Diagnostic catheterization was performed to confirm the absence of CAD and evaluate left ventricular function. A prolonged recording of the venous phase was obtained for guidance of the CS thermographic catheter position. Thereafter, the catheter was advanced from the right femoral vein through an 8Fr sheath to the RA. By manipulating the steering arm at the proximal end, the distal end of the catheter was curved and the tip was positioned approximately 3 cm distally from the CS orifice, based on the freeze-frame of the prolonged recording of the venous phase. An additional recording was performed for accurate placement of the thermographic catheter, if needed. Temperature measurements were performed 5 min after the last injection of contrast medium. Thereafter, the catheter was withdrawn into the mid-RA. Three measurements of CS and RA blood temperature were performed and mean values were calculated. Temperature difference ({Delta}T) was defined as the mean blood temperature of the CS minus the mean blood temperature of the RA. The measurements were performed blind, as the operator performing the manipulation of the catheter was not aware of the exact {Delta}T; all recordings were stored in a computer.

2.4. Statistical analysis
Continuous variables are presented as the mean±1 SD and qualitative variables as the absolute and relative frequencies. Comparisons between the qualitative variables were performed using the {chi}2-test, with Fisher's correction. Comparisons of temperatures between the RA and CS were performed by paired t-test. Comparisons of the temperature measurements between the two groups were performed using the Kruskal-Wallis criteria, whereas the Wilcoxon-Mann-Whitney test was applied for the comparison of temperatures between the RA and the CS within each group. Pearson's correlation was performed in order to determine correlations between the {Delta}T and ejection fraction. All reported p-values are exact, 2-sided, and compared with a significance level of 5%. STATA-6 software was used for these analyses (STATA Corp., College Station, Texas).


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusions
 References
 
The procedure was performed successfully in all subjects with no complications. There were no significant differences in the baseline clinical characteristics between the study groups (Table 1). Left ventricular ejection fraction (EF) was significantly lower in patients with DCM compared to the controls (27.84±6.99 vs 55.41±7.05%, p<0.01).


View this table:
[in this window]
[in a new window]

  		Table 1 Clinical characteristics of the study population

 
3.1. Temperature measurements
The three measurements obtained for the determination of the CS blood temperature were constant in each patient, varying by only 0.005 °C (SD 0 to 0.0335 °C). Similar results were observed in the RA blood temperature (SD 0 to 0.03 °C).

The mean blood temperature was lower in the RA compared with the CS in patients with DCM (36.86±0.54 °C vs 37.11±0.54 °C, p<0.01) and in the controls (36.77±0.81 °C vs 36.92±0.77 °C, p<0.01). {Delta}T was significantly greater in patients with DCM compared to the controls (0.25±0.09 vs 0.14±0.07 °C, p<0.01) (Fig. 1).


Figure 01
View larger version (10K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Temperature difference ({Delta}T) in patients with DCM compared with the controls. The bottom of the box represents the first quartile; the top of the box represents the third quartile, and the line in the box represents the median value of {Delta}T.

 
{Delta}T and EF were inversely correlated in the whole study population (R=0.59, p<0.01) and in patients with DCM (R=0.43, p=0.03) (Fig. 2). There was no correlation between the left ventricular mass and {Delta}T (p=0.70).


Figure 02
View larger version (10K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Correlation of the temperature difference ({Delta}T) and left ventricular ejection fraction (EF) in the DCM patients (R=0.43, p=0.03).

 
3.2. CRP measurements
The levels of CRP were similar between the 2 groups (DCM: 0.95±0.50 mg/dL vs control: 1.33±1.32 mg/dL, p=0.83). We categorized patients with idiopathic DCM into two groups using a CRP cut-off value of ≤1 mg/dL. There were no differences in the demographic characteristics between these two subgroups (Table 2). {Delta}T in patients with high CRP (n=15) was less (0.21±0.06 °C) compared to patients with low CRP (n=10; 0.30±0.08 °C) (p=0.01). Patients with high CRP had lower temperature in the right atrium and coronary sinus compared to patients with low CRP (37.04±0.52 °C vs 36.59±0.46 °C, p=0.04 and 37.25±0.52 °C vs 36.90±0.50 °C, p=0.11, respectively). Both groups had higher {Delta}T compared to the control group (Fig. 3). Finally, a negative correlation was found between the {Delta}T and CRP levels in patients with idiopathic DCM (R=0.57, p<0.01). There was no relation between the EF and CRP values (p=0.68).


View this table:
[in this window]
[in a new window]

  		Table 2 Clinical characteristics in DCM patients according to the CRP level

 


Figure 03
View larger version (11K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Temperature difference ({Delta}T) in the DCM group according to the CRP level compared with the control group. The bottom of the box represents the first quartile; the top of the box represents the third quartile, and the line in the box represents the median value of {Delta}T. (CRP=C-reactive protein).

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusions
 References
 
The main findings of our study are that patients with DCM have increased CS blood temperature compared to the controls, and this increase in blood temperature is inversely correlated with the mechanical performance of the left ventricle. Moreover, systemic inflammatory activation is inversely correlated with the CS blood temperature.

A possible explanation for these findings is the reduced mechanical efficiency of the left ventricle in patients with DCM. Previous studies have demonstrated that the ‘wasted’ energy in the failing myocardium is not transformed to kinetic energy, but is rather lost by heat production [2]. The degree to which energy is converted into mechanical work depends on the mechanical efficiency of the left ventricle and is reduced in the presence of left ventricular systolic dysfunction. In patients with DCM, the reduced mechanical efficiency of the heart may lead to increased myocardial heat production and eventually to increased temperature of the CS venous blood. Our findings are consistent with previous studies in patients with heart failure. Indeed, the increase in CS blood temperature is inversely correlated to the left ventricular ejection fraction, as in heart failure more energy is converted to heat instead of mechanical work [2].

In the present study, patients with DCM and low CRP levels had higher {Delta}T. Although it has been recognized that in patients with DCM inflammation has a significant prognostic value, there are several other factors which may have an effect, such as cytotoxic, metabolic, and familial mechanisms [1,6,9-15]. Histopathological observations in patients with end stage idiopathic dilated cardiomyopathy have shown that there is diffuse fibrosis rather than inflammatory cell infiltration [16]. Indeed, in this study we found an increased {Delta}T in patients with low CRP levels, which suggests that in patients with extensive fibrosis, associated with decreased contractility of the left ventricle, more heat is produced from the myocardium. A possible explanation might be that in patients with end stage DCM, the ‘mechanical’ efficiency is reduced even more and more energy is ‘wasted’ as heat. It would be interesting to monitor serial changes in {Delta}T according to the stage of heart failure and possibly correlate the changes of {Delta}T with CRP fluctuations. However, this was beyond the scope of the present study.

The results of the present study have several clinical implications. Firstly, CS temperature could be used to monitor the acute effect of pharmaceutical agents for the treatment of patients with DCM. Secondly, the measurement of CRP levels in the peripheral blood could provide information on heat production from the myocardium. Low levels of CRP would be indicative of an elevated {Delta}T, suggesting a need for aggressive treatment of these patients. Finally, these results justify the performance of a clinical study, to investigate the impact of the measurement of myocardial heat production as an additional marker for the risk stratification of patients with DCM.

4.1. Limitations of the study
We measured the temperature of the blood in the CS and RA and an increased {Delta}T was found in patients with DCM. We did not measure the aortic or left main blood temperature and we used the RA blood temperature as a reference. We have previously reported that the difference in blood temperature between the CS and left main coronary artery was not significantly different compared with the difference in blood temperature between the CS and RA blood, while there was a strong correlation between these differences in temperature [5]. Although the flow conditions might be altered in the pulmonary circulation in patients with DCM, due to low cardiac output, myocardial perfusion conditions at baseline do not change in patients with DCM compared to the controls [17]. The second issue regarding the findings of the current study is related to the possible effect of the increased left ventricular dimensions and mass on the coronary circulation. However, there was no correlation between the left ventricular mass with temperature measurements. In addition, magnetic resonance imaging studies have shown that baseline myocardial blood flow is not significantly different between patients with DCM and healthy subjects [17].

Regarding the study population, we observed that patients with DCM and high CRP had a higher incidence of hypercholesterolemia, although this was not statistically significant. Since only 8 patients in the DCM group had hypercholesterolemia no firm conclusions can be drawn about a possible relationship between hypercholesterolemia and CRP levels in patients with DCM from the present study. Moreover, the interaction of statins with CRP is uncertain as only 3 patients received statins. Although the incidence of diabetes mellitus was similar between the groups, the majority of patients in the control group had hypertension. The subjects included in the control group underwent coronary angiography for the evaluation of chest pain. These subjects may not be considered as ‘normals’, we only excluded the presence of coronary artery disease by angiography. Accordingly, the results of the present study might be underestimated as the CS temperature is also increased in patients with coronary artery disease [5].

Finally, the increased coronary sinus temperature observed in patients with DCM needs to be further explored in relation to other inflammatory markers, such as brain natriuretic peptide, which are more widely applicable.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
References
 
In the present study, in patients with idiopathic dilated cardiomyopathy, increased heat production from the myocardium, as estimated from the coronary sinus blood temperature, was demonstrated. It seems that the reduced mechanical efficiency of the failing myocardium results in increased heat production. Interestingly there was no correlation with systemic inflammatory activation. The results of the present study justify the performance of additional studies to investigate the role of myocardial heat production in the treatment and prognosis of patients with dilated cardiomyopathy.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 

  1. Lamparter S., Grimm W. Predictive value of high-sensitivity C-reactive protein in patients with idiopathic dilated cardiomyopathy. Pacing Clin Electrophysiol (2005) 28(Suppl_1):S233–S236.[CrossRef][Medline]
  2. Stewart J.T., Simpson I.A., Smith R.E., Callicott C., Gray H.H., Camm A.J. Left ventricular energetics: heat production by the human heart. Cardiovasc Res (1993) 27:1024–1032.[Abstract/Free Full Text]
  3. Stewart J.T., Gray H.H., Calicott C., Smith R.E., Camm A.J. Heat production by the human left ventricle: measurement by a thermodilution technique. Cardiovasc Res (1990) 24:418–422.[Abstract/Free Full Text]
  4. Stewart J.T., Gray H.H., Camm A.J. Measurement of coronary sinus flow by thermodilution: observations on the effect of respiration and a review of the potential sources of error. Cathet Cardiovasc Diagn (1989) 17:207–211.[CrossRef][Web of Science][Medline]
  5. Stefanadis C., Tsiamis E., Vaina S., et al. Temperature of blood in the coronary sinus and right atrium in patients with and without coronary artery disease. Am J Cardiol (2004) 93:207–210.[CrossRef][Web of Science][Medline]
  6. Kaneko K., Kanda T., Yamauchi Y., et al. C-Reactive protein in dilated cardiomyopathy. Cardiology (1999) 91:215–219.[CrossRef][Web of Science][Medline]
  7. Schiller N.B. Two-dimensional echocardiographic determination of left ventricular volume, systolic function, and mass. Summary and discussion of the 1989 recommendations of the American Society of Echocardiography. Circulation (1991) 84:I280–I287.[Web of Science][Medline]
  8. Stefanadis C., Diamantopoulos L., Vlachopoulos C., et al. Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo: a new method of detection by application of a special thermography catheter. Circulation (1999) 99:1965–1971.[Abstract/Free Full Text]
  9. Cooper L.T. Jr., Gersh B.J. Viral infection, inflammation, and the risk of idiopathic dilated cardiomyopathy: can the fire be extinguished? Am J Cardiol (2002) 90:751–754.[CrossRef][Web of Science][Medline]
  10. Devaux B., Scholz D., Hirche A., Klovekorn W.P., Schaper J. Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure. Eur Heart J (1997) 18:470–479.[Abstract/Free Full Text]
  11. Kuhl U., Noutsias M., Seeberg B., Schultheiss H.P. Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy. Heart (1996) 75:295–300.[Abstract/Free Full Text]
  12. Noutsias M., Seeberg B., Schultheiss H.P., Kuhl U. Expression of cell adhesion molecules in dilated cardiomyopathy: evidence for endothelial activation in inflammatory cardiomyopathy. Circulation (1999) 99:2124–2131.[Abstract/Free Full Text]
  13. Noutsias M., Pauschinger M., Poller W.C., Schultheiss H.P., Kuhl U. Current insights into the pathogenesis, diagnosis and therapy of inflammatory cardiomyopathy. Heart Fail Monit (2003) 3:127–135.[Medline]
  14. Pankuweit S., Ruppert V., Maisch B. Inflammation in dilated cardiomyopathy. Herz (2004) 29:788–793.[CrossRef][Web of Science][Medline]
  15. Anand I.S., Latini R., Florea V.G., et al. C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation (2005) 112:1428–1434.[Abstract/Free Full Text]
  16. de Leeuw N., Ruiter D.J., Balk A.H., de Jonge N., Melchers W.J., Galama J.M. Histopathologic findings in explanted heart tissue from patients with end-stage idiopathic dilated cardiomyopathy. Transpl Int (2001) 14:299–306.[Web of Science][Medline]
  17. Watzinger N., Lund G.K., Saeed M., et al. Myocardial blood flow in patients with dilated cardiomyopathy: quantitative assessment with velocity-encoded cine magnetic resonance imaging of the coronary sinus. J Magn Reson Imaging (2005) 21:347–353.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Toutouzas, K.
Right arrow Articles by Stefanadis, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Toutouzas, K.
Right arrow Articles by Stefanadis, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?