Cardiovascular Ultrasound BioMed Central

Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular diseases in urban communities. The potential detrimental effects are both acute and chronic having a strong impact on morbidity and mortality. The acute exposure to pollutants has been linked to adverse cardiovascular events such as myocardial infarction, heart failure and life-threatening arrhythmias. The long-terms effects are related to the lifetime risk of death from cardiac causes. The WHO estimates that air pollution is responsible for 3 million premature deaths each year. The evidence supporting these data is very strong nonetheless, epidemiologic and observational data have the main limitation of imprecise measurements. Moreover, the lack of clinical experimental models makes it difficult to demonstrate the individual risk. The other limitation is related to the lack of a clear mechanism explaining the effects of pollution on cardiovascular mortality. In the present review we will explore the epidemiological, clinical and experimental evidence of the effects of ozone on cardiovascular diseases. The pathophysiologic consequences of air pollutant exposures have been extensively investigated in pulmonary systems, and it is clear that some of the major components of air pollution (e.g. ozone and particulate matter) can initiate and exacerbate lung disease in humans [1]. It is possible that pulmonary oxidant stress mediated by particulate matter and/or ozone (O3) exposure can result in downstream perturbations in the cardiovasculature, as the pulmonary and cardiovascular systems are intricately associated, and it is well documented that specific environmental toxins (such as tobacco smoke [2]) introduced through the lungs can initiate and/or accelerate cardiovascular disease development. Indeed, several epidemiologic studies have proved that there is an association between PM and O3 and the increased incidence of cardiovascular morbidity and mortality [3]. Most of the evidence comes from studies of ambient particles concentrations. However, in Europe and elsewhere, the air pollution profile has gradually changed toward a more pronounced photochemical component. Ozone is one of the most toxic components of the photochemical air pollution mixture. Indeed, the biological basis for these observations has not been elucidated. In the present review, the role of ozone as chemical molecule will be firstly considered. Secondly, pathogenetic mechanisms connecting the atmospheric ozone level and cardiovascular pathology will be examined. Thirdly, the literature relating hospitalization frequency, morbidity and mortality due to cardiovascular causes and ozone concentration will be studied. The correlation between ozone level and occurrence of acute myocardial infarction will be eventually discussed.


Background
Mitral regurgitation is the most frequently valvular pathology encountered nowadays in clinical practice [1]. During the recent decades, there has been a major change not only in the etiology of mitral regurgitation which is now predominantly of degenerative and ischemic origin [2], but also in the non-invasive assessment of the severity and mechanisms responsible for mitral regurgitation by means of transesophageal echocardiography [1,3].
Surgical repair is the most widely used treatment strategy for the correction of mitral regurgitation caused by mitral valve prolapse [4]. Although repair of mitral valve is feasible in up to 95% of the patients with mitral regurgitation of degenerative origin [5], it has been traditionally accepted that prolapse of both mitral valve leaflets is associated with a more complicated repair procedure. On the other hand, repair of the prolapse of the anterior leaflet of mitral valve is technically more demanding and this might lead to less favourable results as compared to the repair of the prolapse of posterior leaflet [6].
Application of new repair techniques for the surgical correction of mitral regurgitation due to the prolapse of anterior leaflet has resulted effective and has positively influenced the postoperative outcome, despite a lack of standardization of the surgical approach. Evidence on the postoperative outcome after surgical repair of mitral regurgitation caused by involvement of anterior mitral leaflet as compared to the posterior mitral leaflet has been limited.

Objective
We sought to compare residual mitral regurgitation after repair of anterior leaflet (isolated or not) with residual mitral regurgitation after repair of posterior leaflet in patients undergoing valve repair due to mitral regurgitation caused by mitral valve prolapse.

Source of information
Relevant information for this study was obtained from the database of patients admitted and treated at Ospedale Pasquinucci, IFC-CNR, Massa, Italy.

Study population
Eligible for this study were all patients with severe mitral regurgitation due to mitral valve prolapse who underwent for the first time surgical repair of mitral valve and presented with residual mitral regurgitation ≤ 2+ as assessed by means of post pump transesophageal echocardiography from January 2004 to October 2005, at Ospedale Pasquinucci, Massa, Italy.
Excluded from this study were patients in whom the myocardial ischemia could have contributed mitral regurgita-tion as well patients who concomitantly underwent other cardiac or vascular surgical procedures such as aorto-coronary bypass surgery, other cardiac valve surgery, surgical interventions for disease of abdominal or thoracic aorta or patients who were surgically treated for cardiac congenital diseases. We did not impose any restriction criteria regarding clinical presentation, age, or accompanying medical conditions. Two groups were defined according to the involvement of mitral valve leaflets: group 1, consisting of patients with anterior leaflet prolapse (isolated or not); and group 2, consisting of patients with isolated posterior leaflet prolapse.
This was a retrospective study. However, all data have been collected and entered into the hospital database in a prospective manner.

Methodology used for the measurement of mitral regurgitation
We employed a qualitative assessment of the severity of mitral regurgitation [7]. Transthoracic echocardiography was performed with a Vivid 7 echo machine, a 3-MHz probe. Tranesophageal echocardiography was performed with Philips Sonos 7500 echo machine, a 3-MHz probe.

Follow-up
All patients were examined by means of transthoracic and transesophageal echocardiography before and after intervention as well as before and after cardiopulmonary bypass. Physicians were unaware of the surgical result. Residual mitral regurgitation after cardiopulmonary bypass was graded from 1+ to 4+.

Statistical analysis
All data presented are shown as mean ± standard deviation or numbers (percentages). To compare the differences between groups, we used student t test for continuous data and chi-square or Fisher's exact test for categorical data, as appropriate. To identify the independent role of anterior leaflet involvement on the residual mitral regurgitation after valve repair, a logistic regression model was build. Statistical significance was accepted for a two-tailed P < 0.05.

Baseline clinical characteristics
A total of 70 patients (18 patients included in group 1 and 52 patients included in group 2) were analyzed. Thirty percent of the patients were women. Mean age of study patients was 63.5 ± 11.5 years old. Patients in group 1 were older compared to patients in group 2 but the difference was not statistically significant (P = 0.052). All patients presented with New York Heart Association (NYHA) class III or IV. About 28% of the patients had dia-betes mellitus and about 45% of the patients suffered from arterial hypertension. Forty percent of had dyslipidemia while 19% of the patients were smokers.

Baseline echocardiographic characteristics
From the total study population, half of the patients had mitral regurgitation grade 3+ and the other half had mitral regurgitation grade 4+. Systolic pressure in the pulmonary artery was 40.4 ± 13.7 mmHg in group 1 and 41.1 ± 8.8 mmHg in group 2. Left atrium diameter was comparable among patients in group 1 and group 2 (47.2 mm and 45.4 mm, respectively). Mean value of left ventricle ejection fraction was 59.3% among patients in group 1 and 59.1% among patients in group 2. There were no significant differences among patients in the two study groups regarding baseline echocardiographic characteristics as shown in Table 1.

Postoperative outcome
Data on the postoperative outcome of study patients are shown in Table 2. Eleven patients in group 1 had residual mitral regurgitation 1+/2+ while 7 patients had no residual mitral regurgitation. Seventeen patients in group 2 had residual mitral regurgitation 1+/2+ and 35 patients had no residual mitral regurgitation. The proportion of patients with residual mitral regurgitation 1+/2+ was higher among patients in group 1 as compared to patients in group 2 (61.1% vs. 32.7%, respectively; P = 0.034). In the analysis of logistic regression, in which residual mitral regurgitation was entered as a response variable, prolapse of anterior leaflet was identified as an independent predictor or residual mitral regurgitation 1+/2+ (odds ratio, 4.0; 95% confidence interval, 1.14 to 14.04; P = 0.03).
No deaths occurred among patients included in this study. There were no differences among patients included in group 1 and patients included in group 2 regarding the need of reintervention, length of stay in intensive care unit and total hospital length of stay. None of the patients in group 1 and one patient in group 2 underwent re-operation for mitral valve replacement.

Discussion
The superiority of valve sparing techniques as compared to valve replacement for the treatment of mitral regurgitation has been widely demonstrated with regard to more favourable mortality and morbidity rates [8]. Reconstructive procedures ensure a more effective and durable competency of the repaired mitral valve [8]. However, early experiences with mitral valve repair in the presence of anterior leaflet prolapse have been less favourable due to more complex mechanisms of valvular incompetence and more demanding repairing techniques. Prolapse of the anterior leaflet is more difficult to repair because it is hardly possible to perform a resection of the anterior leaflet. The height of the chordae underlying the anterior leaflet must be assessed and chords may be grossly elongated or ruptured and make the AML flail. Correction of anterior leaflet prolapse, can be more difficult than posterior leaflet repair; redundancy of the posterior leaflet lends itself to plication or segmental excision, but prolapsing portions of the anterior leaflet are often not redundant nor amenable to excision. Poor results after anterior leaflet resections have led to a variety of techniques including chordal transposition, chordal shortening, and chordal replacement. The aetiology and responsible mechanisms might be negative prognostic factors for the success of mitral valve repair and could lead to a higher incidence of recurrent mitral regurgitation and need for reintervention.
We studied patients who underwent repair of mitral valve for mitral regurgitation due to mitral valve prolapse. We found that patients with prolapse of the anterior leaflet had a higher proportion of residual mitral regurgitation 1+/2+ as compared to patients with prolapse of posterior leaflet after mitral valve repair. In hospital mortality in our group of patients was 0%. Duebener et al. studied 160 patients with mitral regurgitation due to mitral valve prolapse who underwent mitral valve repair and showed that there were no differences regarding mortality and need for reintervention among patients with anterior leaflet prolapse versus patients with posterior leaflet prolapse. Mortality was 4.2% and 0%, respectively in the group of patients with anterior and posterior leaflet prolapse in the above-mentioned study [9]. De Bonis et al. have demonstrated comparable long-term results after repair with different techniques of anterior leaflet prolapse versus posterior leaflet prolapse [10]. While Fukui et al. demonstrated in a population of 26 patients who were followedup for 3.7 years a significant increase in the deterioration of residual mitral regurgitation after repair of anterior mitral leaflet as compared to the posterior mitral leaflet [11]. The reasons for the differences between the results of our study and the results of the abovementioned studies might be found in the different characteristics of patients included in theses studies, surgical techniques used, and duration of follow-up. In a recent analysis, we found that the presence of less than moderate residual mitral regurgitation after valve repair was associated with a non significant trend toward an increased incidence of early adverse events as compared to the absence of residual mitral regurgitation [12].

Conclusion
Among patients undergoing surgical correction of mitral regurgitation due to mitral valve prolapse, repair of anterior leaflet was associated with a higher proportion of residual mitral regurgitation 1+/2+ as compared to the repair of posterior leaflet. The clinical significance of residual mitral regurgitation 1+/2+ in this patient population is not known.