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European Journal of Heart Failure 2006 8(4):400-403; doi:10.1016/j.ejheart.2005.12.006
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© 2006 European Society of Cardiology

The influence of sex on right ventricular dysfunction in patients with severely depressed left ventricular ejection fraction

Manuel Martínez-Sellés*, Marta Domínguez Muñoa, Esther Martínez, Miguel Angel García Fernández and Eulogio García

Cardiology Department. Hospital Universitario Gregorio Marañón Dr. Esquerdo, 46. 28007 Madrid, Spain

* Corresponding author. Tel./fax: +34 915868276. E-mail address: mmselles{at}secardiologia.es


   Abstract
Top
 Abstract
1. Methods
 2. Results
 3. Discussion
 4. Conclusion
 References
 
Aim: To assess the influence of sex on right ventricular dysfunction (RVD) in patients with severe left ventricular systolic dysfunction.

Methods and results: We studied 385 consecutive patients with left ventricular ejection fraction (LVEF) <0.35. All patients underwent invasive measurement of right ventricular and pulmonary artery pressures and evaluation of RVD by standard transthoracic echocardiography.

Female patients (n=84, 21.8%) were significantly older than male patients (62.0±11.4 vs. 58.2±10.7 years), p=0.005. The prevalence of RVD was lower in women (26.5%) than in men (38.9%), p=0.03; both in patients with and without coronary artery disease (19.4% vs. 34.5% and 31.9% vs. 44.4%, respectively). Haemodynamic parameters and LVEF were similar in men and women. Low LVEF, pulmonary systolic pressure, degree of mitral regurgitation, male sex, and absence of significant coronary artery disease were independently correlated with RVD.

Conclusion: Women with severe left ventricular systolic dysfunction have less RVD than men, despite similar haemodynamic parameters and LVEF.

Key Words: Sex • Right ventricle • Systolic dysfunction

Received February 17, 2005; Revised September 20, 2005; Accepted December 20, 2005

Although several studies have shown a better prognosis for women with systolic heart failure than for men [1-6], the reasons for this are largely unknown. In a previous study, we found that severe left ventricular systolic dysfunction is an independent predictor of mortality in men but not in women with heart failure [7] suggesting sex-related differences in the adaptation to a low left ventricular ejection fraction (LVEF).

It has been demonstrated that right ventricular dysfunction (RVD) is a crucial determinant of prognosis in patients with left ventricular systolic dysfunction and chronic heart failure. Right ventricular ejection fraction predicts mortality in patients with moderate heart failure [8] and is the variable with the highest short-term prognostic value in patients with severe chronic heart failure [9,10]. It has an even higher prognostic value than mean peak oxygen consumption [9]. The prognostic value of right ventricular ejection fraction has been confirmed at rest [8-10], during exercise [10], and after acute vasodilator administration [11]. In addition, right ventricular dilatation also correlates with plasma levels of norepinephrine and atrial natriuretic peptide [12], neurohormones which are recognized prognostic markers in heart failure patients.

The aim of this study was to assess the influence of sex on RVD in patients with severe left ventricular systolic dysfunction.


   1. Methods
Top
 Abstract
 1. Methods
2. Results
 3. Discussion
 4. Conclusion
 References
 
All consecutive patients who underwent invasive measurement of right ventricle and pulmonary artery pressures between September 1996 and December 2003 in the haemodynamic laboratory of our institution (a University Hospital with 1917 beds and a primary catchment population of 636,302) [13] were included in this study. Patients with congenital heart disease or previous cardiac transplantation were excluded. A total of 584 patients underwent 771 invasive measurements, of these 385 patients (65.9%) with severe left ventricular systolic dysfunction (LVEF) <0.35 were included in the study. The study was approved by the hospital ethics committee.

LVEF and RVD were assessed by transthoracic echocardiography, using either Sonos 5500 (Philips Technologies, Andover, Massachusetts, USA) or Acuson Sequoia (Siemens Technologies, Mountain View, California, USA) instruments. Both instruments were equipped with harmonic imaging, multi-frequency transducer, and pulsed and continuous wave Doppler. The standard protocol of our echocardiography laboratory was used to assess RVD. This protocol specifies that when right ventricular systolic dysfunction is suspected by the echocardiographer, it should be confirmed either by the presence of a) right ventricular end-diastolic diameter >40 mm, measured in the apical four chamber view [14], or b) low right ventricular ejection fraction based on tricuspid annular motion with a systolic annular velocity <11.5 cm s–1 [15]. RVD was recorded as a dichotomised variable.

Both mitral and tricuspid regurgitation were quantified using the effective regurgitant orifice area [16,17]. Haemodynamic parameters were measured invasively by performing pulmonary artery catheterization with a balloon flotation catheter passed into the pulmonary circulation under fluoroscopic guidance. Cardiac output was determined using the thermodilution method and the mean of at least three readings was recorded. Significant coronary artery disease was considered to be present if there was ≥70% lumen narrowing of a major epicardial artery or its branches. All angiographic measurements were obtained by quantitative off-line analysis. Invasive cardiologists with more than 10 years experience were responsible for interpreting the haemodynamic and angiographic results. Twenty patients who did not undergo coronary angiography were included in the group with no significant coronary disease. Of these 20 patients, 12 had at least one non-invasive test with no ischaemia, seven were aged <50 years and had no risk factors, and one was 52 years old and had amyloidosis. However, the results were similar whether or not these 20 patients were included in the analysis (data not shown).

1.1. Statistical analysis
Means (±S.D.) are reported for continuous variables. The chi-square test was used to assess the significance of the differences between proportions, and Student's t-test was used for comparisons between means. The correlation of variables with RVD was tested using logistic regression multivariate analysis that included age, sex, presence of coronary artery disease, degree of left ventricular dilatation, LVEF, degree of mitral regurgitation, invasively measured pulmonary artery systolic pressure, and the interaction between sex and coronary artery disease. All tests were two-tailed. The SPSS statistical program version 11.0 for Windows was used for statistical analysis (SPSS Inc., Chicago, Illinois, USA). A p value <0.05 was considered significant.


   2. Results
Top
 Abstract
 1. Methods
 2. Results
3. Discussion
 4. Conclusion
 References
 
Mean patient age was 59.0±11.0 years (range: 23 to 84), there were 84 women (21.8%) and 301 men. Coronary angiography was performed in 365 patients (94.8%). Baseline characteristics according to sex are shown in Table 1. Female patients were significantly older and tended to have a lower prevalence of significant coronary artery disease than men (42.9% vs. 54.8%), p=0.05.


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  		Table 1 Baseline characteristics and pharmacological treatment received during admission according to sex

 
All patients had recently undergone echocardiography (median 6 days). Women had a lower prevalence of RVD (Table 2); this lower prevalence was true for both women with coronary artery disease (19.4% vs. 34.5% in men) and those without (31.9% vs. 44.4% in men). We found no significant sex-related differences in haemodynamic, or other echocardiographic parameters (LVEF, tricuspid regurgitation, mitral regurgitation) (Table 2); however severe left ventricular dilatation (>65 mm) was more prevalent in men than in women (41.2% vs. 28.6%, p=0.04). Multivariate logistic regression analysis showed that low LVEF, pulmonary systolic pressure, degree of mitral regurgitation, male sex, and absence of significant coronary artery disease were independently correlated with RVD (Table 3). Men had RVD more frequently than women (OR 1.9-95% CI 1.1-3.5, p=0.03) and we found no significant interaction between sex and coronary artery disease (p=0.9).


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  		Table 2 Haemodynamic parameters and transthoracic echocardiography, data according to sex

 


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  		Table 3 Variables independently correlated with right ventricle dilatation/hypocontractility

 

   3. Discussion
Top
 Abstract
 1. Methods
 2. Results
 3. Discussion
4. Conclusion
 References
 
The better prognosis of heart failure due to left ventricular systolic dysfunction in women compared with men [1-6] remains unexplained. Although some authors have focused on differences in LVEF [1], it has been shown that differences in mortality persist despite similar LVEF [2,7]. Our cohort of patients with severe left ventricular systolic dysfunction, all of whom underwent invasive measurement of haemodynamic parameters with coronary angiography performed in 95%, is an ideal sample in which to look for sex-related differences in adaptation to left ventricular systolic dysfunction.

We found that women who had similar haemodynamic parameters and LVEF to men, presented with less right ventricular dysfunction. Although the prevalence of left ventricular dilatation was similar in both sexes, the women had severe left ventricular dilatation less frequently and tended to have less coronary artery disease, despite being older than the men. Since differences in RVD were present independently of the aetiology and the degree of left ventricular systolic dysfunction, the possibility of independent sex-related biological factor(s) that could confer some right ventricular protection during left systolic dysfunction in women should be considered.

RVD is an important marker of poor prognosis in patients with severely depressed LVEF [8-10]. Further, Ghio et al. showed that the prognostic value of right ventricular ejection fraction is not only independent but additive to pulmonary artery pressure in patients with chronic heart failure [18]. Therefore, this relative right ventricular protection in women can be added to the list of female-related advantages in heart failure, systolic dysfunction pathology and pathophysiology, as recently described [19-23].

The present study suggests that female sex per se is associated with a lower RVD. This may be due to the ability of women to manage volume overload better, particularly in women with previous pregnancies, since the haemodynamic and structural cardiac changes in pregnancy are similar to those associated with exercise and persist for up to 1 year after delivery [24]. Since exercise improves many pathophysiological aspects of heart failure [25,26], it is conceivable that pregnancy-related cardiovascular and neurohormonal changes could condition the heart, and especially the right ventricle, to adapt to future left ventricular systolic dysfunction better.

Our study has some limitations. First, since evaluation of the right ventricle was performed retrospectively, milder forms of RVD were probably not included. Second, we had no data about previous pregnancies; however, since the mean age of the women was 62 years, a high percentage of previous pregnancies could be expected. Finally, this study was performed in a single, tertiary centre, so generalisation of our findings to larger populations with systolic dysfunction may not be appropriate. Nevertheless, our study has several important strengths. First, it was based on a large sample of patients with left ventricular systolic dysfunction without age restriction. Second, all patients had invasively measured pulmonary pressures and other haemodynamic data. Finally, ischaemic aetiology was clearly identified since 95% of the patients had a coronary angiography.


   4. Conclusion
Top
 Abstract
 1. Methods
 2. Results
 3. Discussion
 4. Conclusion
References
 
Women with severe left systolic dysfunction have less RVD than men despite similar haemodynamic parameters and LVEF.


   References
Top
 Abstract
 1. Methods
 2. Results
 3. Discussion
 4. Conclusion
 References
 

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