Accepted Manuscript Epidemiology of acquired valvular heart disease Bernard Iung, MD Alec Vahanian, MD PII:
S0828-282X(14)00168-8
DOI:
10.1016/j.cjca.2014.03.022
Reference:
CJCA 1154
To appear in:
Canadian Journal of Cardiology
Received Date: 29 January 2014 Revised Date:
19 February 2014
Accepted Date: 7 March 2014
Please cite this article as: Iung B, Vahanian A, Epidemiology of acquired valvular heart disease, Canadian Journal of Cardiology (2014), doi: 10.1016/j.cjca.2014.03.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
RI PT
Epidemiology of acquired valvular heart disease
Bernard Iung, MD; Alec Vahanian, MD
Word count 235 words 4619 words 259 words 1879 words
Total
6992 words
EP
TE D
Abstract: Text: Tables (2): References (70): Figures (4)
M AN U
SC
Cardiology Department, Bichat Hospital, and Paris 7 Diderot University, Paris, France
AC C
Bernard Iung, MD Cardiology Department, Bichat Hospital, AP-HP, 46 rue Henri Huchard, 75018 Paris, France Tel : +33 1 40 25 67 60 Fax : +33 1 40 25 67 32 E-mail : [email protected]
1
ACCEPTED MANUSCRIPT Brief summary
The prevalence of valvular disease is 2.5% in industrialized countries. It increases markedly after the age of 65, in particular for aortic stenosis and mitral regurgitation, due to the
RI PT
predominance of degenerative etiologies. The incidence of infective endocarditis is stable, but patients are older and staphylococcus is becoming the microorganism most frequently
responsible. In developing countries, rheumatic heart disease remains the leading cause of
SC
valvular disease and is more frequently detected using systematic echocardiographic
AC C
EP
TE D
M AN U
screening.
2
ACCEPTED MANUSCRIPT Abstract
Population-based studies including systematic echocardiographic examinations are required to assess the prevalence of valvular heart disease. In industrialized countries, the prevalence of
RI PT
valvular heart disease is estimated at 2.5%. Due to the predominance of degenerative
etiologies, the prevalence of valvular disease increases markedly after the age of 65, in
particular with regard to aortic stenosis and mitral regurgitation, which account for 3 in 4
SC
cases of valvular disease. Rheumatic heart disease still represents 22% of valvular heart disease in Europe. The prevalence of secondary mitral regurgitation cannot be assessed
M AN U
reliably but it seems to be a frequent disease.
The incidence of infective endocarditis is around 30 cases per million inhabitants per year. Its stability is associated with marked changes in its presentation. Patients are getting older and staphylococcus is now becoming the microorganism most frequently responsible. Heathcare-
infective endocarditis.
TE D
associated infections are the most likely explanation of changes in the microbiology of
In developing countries, rheumatic heart disease remains the leading cause of valvular heart
EP
disease. Its prevalence is high, between 20 and 30 cases per 1000 subjects when using systematic echocardiographic screening.
AC C
In conclusion, the temporal and geographical heterogeneity illustrates the impact of socioeconomic status and changes in life expectancy on the frequency and presentation of valvular heart disease. A decreased burden of valvular disease would require the elaboration of preventive strategies in industrialized countries and an improvement in the socio-economic environment in developing countries.
3
ACCEPTED MANUSCRIPT The epidemiology of valvular heart disease is difficult to study since most cases of valve disease are chronic and often asymptomatic. The detection of cardiac murmurs lacks sensitivity and specificity. Therefore, assessment of the true prevalence of valvular heart disease requires the performance of systematic echocardiography in a representative
RI PT
population. These constraints account for the small number of series which allow for accurate estimation of the prevalence of valvular heart disease (1).
Population-based series including echocardiographic examinations are now available in
SC
different countries and allow for a better understanding of the wide spectrum of valvular disease, which has been the subject of important changes during the last decades. In addition,
M AN U
specific surveys on valvular disease provide more accurate descriptions of valvular disease, in particular regarding anatomy, mechanisms, severity and consequences, which have a strong influence on their natural history.
TE D
1. Epidemiology of valvular disease in industrialized countries 1.1. Overall profile
The estimation of the overall prevalence of valvular disease in industrialized countries relies
EP
on a population-based study performed in the US, which included 11,911 subjects who underwent echocardiographic examination (2). The age-adjusted prevalence of moderate or
AC C
severe valvular disease was estimated at 2.5% (95% confidence interval 2.2-2.7%). There was no gender difference. The prevalence of valvular disease increased with age: it was < 2% before the age of 65 and then increased to 13.2% after the age of 75. The prevalence according to age is detailed in Figure 1 for the different types of valve diseases. The increased prevalence of valvular disease with age reflects the predominance of so-called degenerative etiologies in industrialized countries. Although widely used, the term "degenerative valve disease" encompasses heterogeneous lesions with regard to
4
ACCEPTED MANUSCRIPT pathophysiology, macroscopic and histological involvement of the valves. The etiology of valvular disease can be ascertained only using prospectively defined echocardiographic analyses. The Euro Heart Survey on valvular heart disease was not conducted in an epidemiologically representative population, but was designed to prospectively assess the
RI PT
detailed clinical and echocardiographic characteristics of patients referred to hospital for the management of vavular heart disease (3). It included 5,001 patients, of whom 72% had native valve disease and 28% had previously undergone valvular intervention. It was performed
SC
during a 4-month period in 2001 in 92 centres in 25 European countries. The distribution of the etiologies of valvular disease in patients referred to hospital is shown in Figure 2. Aortic
M AN U
stenosis (AS) was the most frequent single-valve disease (43%), followed by mitral regurgitation (MR)(32%), aortic regurgitation (AR)(13%) and mitral stenosis (MS)(12%). Degenerative etiology was the leading cause of valvular disease, in 63% of patients and in all European regions (Figure 3). Rheumatic heart disease was the second cause of valvular
TE D
disease and was still present in 22% of patients. Other etiologies accounted for 15% of all cases and comprised mainly infective endocarditis (IE) and inflammatory and congenital heart disease. Radiation-induced and drug-induced valvular disease have been characterized more
1.2 Aortic Stenosis
EP
recently and their prevalence may have been underestimated (4-5)
AC C
1.2.1 Prevalence
Aortic stenosis is the ultimate consequence of calcific aortic disease, which begins with aortic sclerosis and then leads to progressive valve obstruction with an ongoing process of valve remodelling and calcification (6). The prevalence of AS can be reliably assessed from four population-based studies in Europe and the US (2, 7-9). The prevalence of AS was estimated at 0.4% in the largest series including 11,911 patients with systematic echocardiographic examination. It was ≤0.2%
5
ACCEPTED MANUSCRIPT before 65 years and increased to 1.3% between 65 and 74 years and to 2.8% after 75 (Figure 1) (2). The Tromso study included 3,273 patients and reported higher prevalence rates in the elderly: 0.2% between 50 and 59 years, 1.3% between 60 and 69, 3.9% between 70 and 79 and 9.8% between 80 and 89 (9). Differences may be partly due to differences in the severity
RI PT
of valvular diseases included. Nevertheless, the four series consistently showed a straight increase in the prevalence of moderate and severe AS after the age of 65 and high prevalence rates in the elderly (Figure 3).
SC
The Tromso study enables incidence to be analysed from sequential clinical and
echocardiographic evaluations between 1974 and 2008. The annual incidence rate was 4.9 per
M AN U
1000 for the whole study period (9). A Scottish study based on diagnosis at hospital discharge reported more than tenfold lower incidence rates (10). The most plausible explanation for such discrepancies is that hospitalization captures only those patients who present with the most severe presentation of the disease, as compared with systematic screening of the
TE D
population.
There were discrepancies regarding the gender distribution of AS between the study by Nkomo et al, who found a higher sex-adjusted prevalence of AS in men than in women and
EP
the Tromso study, which did not find any significant difference (2, 9). The number of cases of AS is higher in women due to their longer life expectancy.
AC C
The prevalence of AS is expected to increase over the coming decades because of population ageing. The prevalence of AS is likely to remain stable because of the lack of validated strategies aimed at preventing AS or slowing its progression. According to demographic statistics and prevalence rates derived from the US population-based study, the number of subjects aged 75 or older with at least moderate AS is expected to double over the next 50 years in France, increasing from approximately 160,000 to 330,000 (11). The Scottish series already reported an increase in the age and sex-standardized incidence of patients hospitalized
6
ACCEPTED MANUSCRIPT with a diagnosis of AS from 246 per million in 1997 to 365 per million in 2005 (10). AS was by far the most frequently diagnosed valvular disease among patients referred to hospital, which is in accordance with the findings of the Euro Heart Survey (3). The prevalence of AS is influenced by bicuspid aortic valve (BAV), since this congenital
RI PT
disease increases the risk of developing AS. Systematic echocardiographic screening
estimates the prevalence of BAV at 0.6-0.8% in males and 0.2% in females (12-13). The prevalence of BAV is estimated at 1.4% according to US statistics, with an incidence of
SC
54,800 new cases per year in the US (14). BAV seldom causes severe aortic valve disease in childhood, but it considerably increases the risk of aortic valve disease, in particular AS, in
M AN U
the adult. The long-term follow-up of 212 patients with BAV and no initial valve dysfunction demonstrated that aortic valve replacement (AVR) was needed in 24% of them after 20 years, in 3 out of 4 cases because of AS (15). The same study reported an annual incidence of 19/100,000 AVR in the Olmsted County over a 10-year period, the corresponding figure
TE D
being 1370/100,000 in patients with BAV. Mean age at the time of AVR was 67±16 years in patients with tricuspid aortic valve and 49±20 years in those with a BAV (15). The burden of BAV is likely to be underestimated in the adult since the number of cusps may be difficult to
EP
identify on a calcified valve. Systematic examination of explanted valves after AVR for AS showed that BAV accounted for 49% of all valves. Tricuspid valves were more frequent than
AC C
BAV only after the age of 70 (16). 1.2.2. Natural history
The progression of aortic sclerosis is slow, as shown by the 16% rate of progression towards moderate AS and 2.5% toward severe AS during a mean follow-up of 7 years (17). In AS, there is a mean increase of mean gradient of 7 mmHg and a decrease in valve area of 0.1 cm² per year (11). However, the progression may be highly variable in an individual patient and is seldom linear.
7
ACCEPTED MANUSCRIPT The main predictive factors of spontaneous outcome in AS are symptom onset and left ventricular dysfunction. Asymptomatic patients have a good prognosis, with an annual death rate 50 mm, and
S0828-282X(14)00168-8
DOI:
10.1016/j.cjca.2014.03.022
Reference:
CJCA 1154
To appear in:
Canadian Journal of Cardiology
Received Date: 29 January 2014 Revised Date:
19 February 2014
Accepted Date: 7 March 2014
Please cite this article as: Iung B, Vahanian A, Epidemiology of acquired valvular heart disease, Canadian Journal of Cardiology (2014), doi: 10.1016/j.cjca.2014.03.022. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
RI PT
Epidemiology of acquired valvular heart disease
Bernard Iung, MD; Alec Vahanian, MD
Word count 235 words 4619 words 259 words 1879 words
Total
6992 words
EP
TE D
Abstract: Text: Tables (2): References (70): Figures (4)
M AN U
SC
Cardiology Department, Bichat Hospital, and Paris 7 Diderot University, Paris, France
AC C
Bernard Iung, MD Cardiology Department, Bichat Hospital, AP-HP, 46 rue Henri Huchard, 75018 Paris, France Tel : +33 1 40 25 67 60 Fax : +33 1 40 25 67 32 E-mail : [email protected]
1
ACCEPTED MANUSCRIPT Brief summary
The prevalence of valvular disease is 2.5% in industrialized countries. It increases markedly after the age of 65, in particular for aortic stenosis and mitral regurgitation, due to the
RI PT
predominance of degenerative etiologies. The incidence of infective endocarditis is stable, but patients are older and staphylococcus is becoming the microorganism most frequently
responsible. In developing countries, rheumatic heart disease remains the leading cause of
SC
valvular disease and is more frequently detected using systematic echocardiographic
AC C
EP
TE D
M AN U
screening.
2
ACCEPTED MANUSCRIPT Abstract
Population-based studies including systematic echocardiographic examinations are required to assess the prevalence of valvular heart disease. In industrialized countries, the prevalence of
RI PT
valvular heart disease is estimated at 2.5%. Due to the predominance of degenerative
etiologies, the prevalence of valvular disease increases markedly after the age of 65, in
particular with regard to aortic stenosis and mitral regurgitation, which account for 3 in 4
SC
cases of valvular disease. Rheumatic heart disease still represents 22% of valvular heart disease in Europe. The prevalence of secondary mitral regurgitation cannot be assessed
M AN U
reliably but it seems to be a frequent disease.
The incidence of infective endocarditis is around 30 cases per million inhabitants per year. Its stability is associated with marked changes in its presentation. Patients are getting older and staphylococcus is now becoming the microorganism most frequently responsible. Heathcare-
infective endocarditis.
TE D
associated infections are the most likely explanation of changes in the microbiology of
In developing countries, rheumatic heart disease remains the leading cause of valvular heart
EP
disease. Its prevalence is high, between 20 and 30 cases per 1000 subjects when using systematic echocardiographic screening.
AC C
In conclusion, the temporal and geographical heterogeneity illustrates the impact of socioeconomic status and changes in life expectancy on the frequency and presentation of valvular heart disease. A decreased burden of valvular disease would require the elaboration of preventive strategies in industrialized countries and an improvement in the socio-economic environment in developing countries.
3
ACCEPTED MANUSCRIPT The epidemiology of valvular heart disease is difficult to study since most cases of valve disease are chronic and often asymptomatic. The detection of cardiac murmurs lacks sensitivity and specificity. Therefore, assessment of the true prevalence of valvular heart disease requires the performance of systematic echocardiography in a representative
RI PT
population. These constraints account for the small number of series which allow for accurate estimation of the prevalence of valvular heart disease (1).
Population-based series including echocardiographic examinations are now available in
SC
different countries and allow for a better understanding of the wide spectrum of valvular disease, which has been the subject of important changes during the last decades. In addition,
M AN U
specific surveys on valvular disease provide more accurate descriptions of valvular disease, in particular regarding anatomy, mechanisms, severity and consequences, which have a strong influence on their natural history.
TE D
1. Epidemiology of valvular disease in industrialized countries 1.1. Overall profile
The estimation of the overall prevalence of valvular disease in industrialized countries relies
EP
on a population-based study performed in the US, which included 11,911 subjects who underwent echocardiographic examination (2). The age-adjusted prevalence of moderate or
AC C
severe valvular disease was estimated at 2.5% (95% confidence interval 2.2-2.7%). There was no gender difference. The prevalence of valvular disease increased with age: it was < 2% before the age of 65 and then increased to 13.2% after the age of 75. The prevalence according to age is detailed in Figure 1 for the different types of valve diseases. The increased prevalence of valvular disease with age reflects the predominance of so-called degenerative etiologies in industrialized countries. Although widely used, the term "degenerative valve disease" encompasses heterogeneous lesions with regard to
4
ACCEPTED MANUSCRIPT pathophysiology, macroscopic and histological involvement of the valves. The etiology of valvular disease can be ascertained only using prospectively defined echocardiographic analyses. The Euro Heart Survey on valvular heart disease was not conducted in an epidemiologically representative population, but was designed to prospectively assess the
RI PT
detailed clinical and echocardiographic characteristics of patients referred to hospital for the management of vavular heart disease (3). It included 5,001 patients, of whom 72% had native valve disease and 28% had previously undergone valvular intervention. It was performed
SC
during a 4-month period in 2001 in 92 centres in 25 European countries. The distribution of the etiologies of valvular disease in patients referred to hospital is shown in Figure 2. Aortic
M AN U
stenosis (AS) was the most frequent single-valve disease (43%), followed by mitral regurgitation (MR)(32%), aortic regurgitation (AR)(13%) and mitral stenosis (MS)(12%). Degenerative etiology was the leading cause of valvular disease, in 63% of patients and in all European regions (Figure 3). Rheumatic heart disease was the second cause of valvular
TE D
disease and was still present in 22% of patients. Other etiologies accounted for 15% of all cases and comprised mainly infective endocarditis (IE) and inflammatory and congenital heart disease. Radiation-induced and drug-induced valvular disease have been characterized more
1.2 Aortic Stenosis
EP
recently and their prevalence may have been underestimated (4-5)
AC C
1.2.1 Prevalence
Aortic stenosis is the ultimate consequence of calcific aortic disease, which begins with aortic sclerosis and then leads to progressive valve obstruction with an ongoing process of valve remodelling and calcification (6). The prevalence of AS can be reliably assessed from four population-based studies in Europe and the US (2, 7-9). The prevalence of AS was estimated at 0.4% in the largest series including 11,911 patients with systematic echocardiographic examination. It was ≤0.2%
5
ACCEPTED MANUSCRIPT before 65 years and increased to 1.3% between 65 and 74 years and to 2.8% after 75 (Figure 1) (2). The Tromso study included 3,273 patients and reported higher prevalence rates in the elderly: 0.2% between 50 and 59 years, 1.3% between 60 and 69, 3.9% between 70 and 79 and 9.8% between 80 and 89 (9). Differences may be partly due to differences in the severity
RI PT
of valvular diseases included. Nevertheless, the four series consistently showed a straight increase in the prevalence of moderate and severe AS after the age of 65 and high prevalence rates in the elderly (Figure 3).
SC
The Tromso study enables incidence to be analysed from sequential clinical and
echocardiographic evaluations between 1974 and 2008. The annual incidence rate was 4.9 per
M AN U
1000 for the whole study period (9). A Scottish study based on diagnosis at hospital discharge reported more than tenfold lower incidence rates (10). The most plausible explanation for such discrepancies is that hospitalization captures only those patients who present with the most severe presentation of the disease, as compared with systematic screening of the
TE D
population.
There were discrepancies regarding the gender distribution of AS between the study by Nkomo et al, who found a higher sex-adjusted prevalence of AS in men than in women and
EP
the Tromso study, which did not find any significant difference (2, 9). The number of cases of AS is higher in women due to their longer life expectancy.
AC C
The prevalence of AS is expected to increase over the coming decades because of population ageing. The prevalence of AS is likely to remain stable because of the lack of validated strategies aimed at preventing AS or slowing its progression. According to demographic statistics and prevalence rates derived from the US population-based study, the number of subjects aged 75 or older with at least moderate AS is expected to double over the next 50 years in France, increasing from approximately 160,000 to 330,000 (11). The Scottish series already reported an increase in the age and sex-standardized incidence of patients hospitalized
6
ACCEPTED MANUSCRIPT with a diagnosis of AS from 246 per million in 1997 to 365 per million in 2005 (10). AS was by far the most frequently diagnosed valvular disease among patients referred to hospital, which is in accordance with the findings of the Euro Heart Survey (3). The prevalence of AS is influenced by bicuspid aortic valve (BAV), since this congenital
RI PT
disease increases the risk of developing AS. Systematic echocardiographic screening
estimates the prevalence of BAV at 0.6-0.8% in males and 0.2% in females (12-13). The prevalence of BAV is estimated at 1.4% according to US statistics, with an incidence of
SC
54,800 new cases per year in the US (14). BAV seldom causes severe aortic valve disease in childhood, but it considerably increases the risk of aortic valve disease, in particular AS, in
M AN U
the adult. The long-term follow-up of 212 patients with BAV and no initial valve dysfunction demonstrated that aortic valve replacement (AVR) was needed in 24% of them after 20 years, in 3 out of 4 cases because of AS (15). The same study reported an annual incidence of 19/100,000 AVR in the Olmsted County over a 10-year period, the corresponding figure
TE D
being 1370/100,000 in patients with BAV. Mean age at the time of AVR was 67±16 years in patients with tricuspid aortic valve and 49±20 years in those with a BAV (15). The burden of BAV is likely to be underestimated in the adult since the number of cusps may be difficult to
EP
identify on a calcified valve. Systematic examination of explanted valves after AVR for AS showed that BAV accounted for 49% of all valves. Tricuspid valves were more frequent than
AC C
BAV only after the age of 70 (16). 1.2.2. Natural history
The progression of aortic sclerosis is slow, as shown by the 16% rate of progression towards moderate AS and 2.5% toward severe AS during a mean follow-up of 7 years (17). In AS, there is a mean increase of mean gradient of 7 mmHg and a decrease in valve area of 0.1 cm² per year (11). However, the progression may be highly variable in an individual patient and is seldom linear.
7
ACCEPTED MANUSCRIPT The main predictive factors of spontaneous outcome in AS are symptom onset and left ventricular dysfunction. Asymptomatic patients have a good prognosis, with an annual death rate 50 mm, and
