Ad J.J.C. Bogers

Aortic Stenosis in the Elderly: Disease Prevalence and Number of Candidates for Transcatheter Aortic Valve Replacement: A Meta-Analysis and Modeling Study

OBJECTIVES The purpose of this study was to evaluate the prevalence of aortic stenosis (AS) in the elderly and to estimate the current and future number of candidates for transcatheter aortic valve replacement (TAVR). BACKGROUND Severe AS is a major cause of morbidity and mortality in the elderly. A proportion of these patients is at high or prohibitive risk for surgical aortic valve replacement, and is now considered for TAVR. METHODS A systematic search was conducted in multiple databases, and prevalence rates of patients (>75 years) were pooled. A model was based on a second systematic literature search of studies on decision making in AS. Monte Carlo simulations were performed to estimate the number of TAVR candidates in 19 European countries and North America. RESULTS Data from 7 studies (n = 9,723 subjects) were used. The pooled prevalence of all AS in the elderly was 12.4% (95% confidence interval [CI]: 6.6% to 18.2%), and the prevalence of severe AS was 3.4% (95% CI: 1.1% to 5.7%). Among elderly patients with severe AS, 75.6% (95% CI: 65.8% to 85.4%) were symptomatic, and 40.5% (95% CI: 35.8% to 45.1%) of these patients were not treated surgically. Of those, 40.3% (95% CI: 33.8% to 46.7%) received TAVR. Of the high-risk patients, 5.2% were TAVR candidates. Projections showed that there are approximately 189,836 (95% CI: 80,281 to 347,372) TAVR candidates in the European countries and 102,558 (95% CI: 43,612 to 187,002) in North America. Annually, there are 17,712 (95% CI: 7,590 to 32,691) new TAVR candidates in the European countries and 9,189 (95% CI: 3,898 to 16,682) in North America. CONCLUSIONS With a pooled prevalence of 3.4%, the burden of disease among the elderly due to severe AS is substantial. Under the current indications, approximately 290,000 elderly patients with severe AS are TAVR candidates. Nearly 27,000 patients become eligible for TAVR annually.

Development of the origin of the coronary arteries, a matter of ingrowth or outgrowth?

SummaryInconsistencies still exist with regard to the exact mode of development of proximal coronary arteries and coronary orifices. In this regard 15 quail embryos were investigated using a monoclonal anti-endothelium antibody, enabling a detailed study of the development of endothelium-lined vasculature. Coronary orifices emerged at 7–9 days of incubation (Zacchei stages 24–26) and were invariably present at 10 days of incubation (Zacchei stage 27).We never observed more than 2 coronary orifices; these were always single in either of the facing sinuses of the aorta. A coronary orifice was always observed being connected to an already developed proximal coronary artery, which belonged to a peritruncal ring of coronary arterial vasculature. We did not find any coronary orifice without a connection to a proximal coronary artery. Moreover, at 7–9 days of incubation (Zacchei stages 24–26) we observed coronary arteries from the peritruncal ring penetrating the aortic media. In 2 specimen this coronary artery, with a lumen, was in contact with the still intact endothelial lining of the aorta.We conclude that coronary arteries do not grow out of the aorta, but grow into the aorta from the peritruncal ring of coronary arterial vasculature. This throws new light on normal and abnormal development of proximal coronary arteries and coronary orifices.

The impact of prosthesis–patient mismatch on long-term survival after aortic valve replacement: a systematic review and meta-analysis of 34 observational studies comprising 27 186 patients with 133 141 patient-years

AIMS Numerous studies have linked prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) to adverse outcomes. Its correlation with long-term survival has been described but with contradicting results. This systematic review and meta-analysis of observational studies aims to determine the hazard of PPM after AVR. METHODS AND RESULTS The Medline and EMBase databases were searched for English-language original publications. Two researchers independently screened studies and extracted data. Pooled estimates were obtained by random effects model. Subgroup analyses were performed to detect sources of heterogeneity. The search yielded 348 potentially relevant studies; 34 were included comprising 27 186 patients and 133 141 patient-years. Defined by the universally accredited indexed effective orifice area <0.85 cm(2)/m(2), 44.2% of patients were categorized as having PPM. In 34.2 and 9.8% of patients moderate (0.65-0.85 cm(2)/m(2)) and severe (<0.65 cm(2)/m(2)) PPM was present, respectively. Prosthesis-patient mismatch was associated with a statistically significant increase in all-cause mortality (HR = 1.34, 95% CI: 1.18-1.51), but only a trend to an increase in cardiac-related mortality (HR = 1.51, 95% CI: 0.88-2.60) was recognized. Analysis by severity of PPM demonstrated that both moderate and severe PPM increased all-cause mortality (HR = 1.19, 95% CI: 1.07-1.33 and HR = 1.84, 95% CI: 1.38-2.45) and cardiac-related mortality (HR = 1.32, 95% CI: 1.02-1.71 and HR = 6.46, 95% CI: 2.79-14.97). Further analyses showed a consistent effect over separate time intervals during follow-up. CONCLUSION Prosthesis-patient mismatch is associated with an increase in all-cause and cardiac-related mortality over long-term follow-up. We recommend that current efforts to prevent PPM should receive more emphasis and a widespread acceptance to improve long-term survival after AVR.

Validation of the Charlson comorbidity index in patients with operated primary non-small cell lung cancer.

OBJECTIVE To validate the influence of the Charlson comorbidity index (CCI) in patients with operated primary non-small cell lung cancer. METHODS From January 1996 to December 2001, 205 consecutive resections for non-small cell lung cancer were performed at the Erasmus Medical Center Rotterdam. The patients ranged in age from 29 to 82 years, with a mean age of 64 years. In a retrospective study, each patient was scaled according to the CCI and the complications of surgery were determined. RESULTS The hospital mortality was 2.4% (5/205). Of the 205 patients 167 (32.7%) experienced minor complications and 32 (15.6%) major complications. In univariate analysis, gender, grades 3-4 of the CCI, any prior tumor treated in the last 5 years and chronic pulmonary disease were significant predictors of adverse outcome. Multivariate analysis showed that only grades 3-4 of the CCI was predictive (odds ratio=9.8; 95% confidence interval=2.1-45.9). Although only comorbidity grades 3-4 was a significant predictor, for every increase of the comorbidity grade the relative risk of adverse outcome showed a slight increase. CONCLUSION The CCI is strongly correlated with higher risk of surgery in primary non-small cell lung cancer patients and is a better predictor than individual risk factors.

The Ross Procedure A Systematic Review and Meta-Analysis

Background— Reports on outcome after the Ross procedure are limited by small study size and show variable durability results. A systematic review of evidence on outcome after the Ross procedure may improve insight into outcome and potential determinants. Methods and Results— A systematic review of reports published from January 2000 to January 2008 on outcome after the Ross procedure was undertaken. Thirty-nine articles meeting the inclusion criteria were allocated to 3 categories: (1) consecutive series, (2) adult patient series, and (3) pediatric patient series. With the use of an inverse variance approach, pooled morbidity and mortality rates were obtained. Pooled early mortality for consecutive, adult, and pediatric patients series was 3.0% (95% confidence interval [CI], 1.8 to 4.9), 3.2% (95% CI, 1.5 to 6.6), and 4.2% (95% CI, 1.4 to 11.5). Autograft deterioration rates were 1.15% (95% CI, 1.06 to 2.06), 0.78% (95% CI, 0.43 to 1.40), and 1.38%/patient-year (95% CI, 0.68 to 2.80), respectively, and for right ventricular outflow tract conduit were 0.91% (95% CI, 0.56 to 1.47), 0.55% (95% CI, 0.26 to 1.17), and 1.60%/patient-year (95% CI, 0.84 to 3.05), respectively. For studies with mean patient age >18 years versus mean patient age ≤18 years, pooled autograft and right ventricular outflow tract deterioration rates were 1.14% (95% CI, 0.83 to 1.57) versus 1.69% (95% CI, 1.02 to 2.79) and 0.65% (95% CI, 0.41 to 1.02) versus 1.66%/patient-year (95% CI, 0.98 to 2.82), respectively. Conclusions— The Ross procedure provides satisfactory results for both children and young adults. Durability limitations become apparent by the end of the first postoperative decade, in particular in younger patients.

Excellent survival and low incidence of arrhythmias, stroke and heart failure long-term after surgical ASD closure at young age. A prospective follow-up study of 21-33 years

AIMS Although studies have suggested good long-term results, arrhythmias, pulmonary hypertension and left ventricular dysfunction are mentioned as sequelae long-term after surgical atrial septal defect closure at young age. Most studies were performed only by questionnaire and in a retrospective manner. The long-term outcome is very important with regard to future employment and acceptance on insurance schemes. METHODS AND RESULTS One hundred and thirty-five consecutive ASD-patients, operated on in childhood, were studied longitudinally with ECG, echocardiography, exercise testing and Holter-recording 15 (10-22) and 26 (21-33) years after surgery. During follow-up no cardiovascular mortality, stroke, heart failure and no pulmonary hypertension occurred. Symptomatic supraventricular tachyarrhythmias were present in 6% after 15 years, and an additional 2% occurred in the last decade; 5% needed pacemaker implantation. No relation was found between arrhythmias and type of ASD, baseline data, right ventricular dimensions, or age at operation. Left and right ventricular function and dimension remained unchanged. Slightly more patients had right atrial dilatation at last follow-up. Exercise capacity was comparable with the normal Dutch population. CONCLUSIONS The long-term outcome after ASD closure at young age shows excellent survival and low morbidity. The incidence of supraventricular arrhythmias is lower than in natural history studies of ASD patients and also lower than after surgical correction at adult age.

Smoking Cessation Reduces Mortality After Coronary Artery Bypass Surgery: A 20-Year Follow-up Study

OBJECTIVES The goal of this study was to determine the influence of smoking cessation on mortality after coronary artery bypass graft surgery (CABG), which has still not been established clearly. BACKGROUND Cigarette smoking is one of the known major risk factors of coronary artery disease. METHODS One thousand and forty-one patients underwent CABG between 1971 and 1980. The preoperative and postoperative smoking habits of 985 patients (95%) could be retrieved and were analyzed in a multivariate Cox analysis. RESULTS The median follow-up was 20 years (range 13 to 26 years). Smoking status before surgery did not entail an increased risk of mortality: patients who had smoked before surgery and those who had not smoked in the year before surgery had a similar probability of survival. However, smoking cessation after surgery was an important independent predictor of a lower risk of death and coronary reintervention during the 20-year follow-up when compared with patients who continued smoking. In analyses adjusted for baseline characteristics, the persistent smokers had a greater relative risk (RR) of death from all causes (RR 1.68 [95% confidence interval 1.33 to 2.13]) and cardiac death (RR 1.75 [1.30 to 2.37]) as compared with patients who stopped smoking for at least one year after surgery. The estimated benefit of survival for the quitters increased from 3% at five years to 14% at 15 years. The quitters were less likely to undergo repeat CABG or a percutaneous coronary angioplasty procedure (RR 1.41 [1.02 to 1.94]). CONCLUSIONS Patients who continued to smoke after CABG had a greater risk of death than patients who stopped smoking. They also underwent repeat revascularization procedures more frequently. Cessation of smoking is therefore strongly recommended after CABG. Clinicians are encouraged to start or to continue smoking-cessation programs in order to help smokers to quit smoking, especially after CABG.

Psychosocial functioning of the adult with congenital heart disease: a 20–33 years follow-up

AIMS Since knowledge about the psychosocial function of adult patients with congenital heart disease is limited, we compared biographical characteristics, and emotional and social functioning of these patients with that of the reference groups. METHODS AND RESULTS Patients with congenital heart disease (N=362, aged 20-46 years), belonging to five diagnostic groups, were subjected to extensive medical and psychological examination, 20-33 years after their first open heart surgery. All the patients were seen by the same psychologist, who examined their psychosocial functioning using a structured interview and questionnaires. The majority (78%)was living independently and showed favourable outcome regarding the marital status. Among married/cohabitant patients, 25-39-year-olds showed normal offspring rates. None of the 20-24-year-old patients had any children. The offspring rate dropped after the age of 40. The proportion of adult patients with a history of special education was high (27%). Accordingly, patients showed lower educational and occupational levels compared to reference groups. As regard to the emotional and social functioning (leisure-time activities), the sample showed favourable results. CONCLUSIONS Overall, this sample of patients with congenital heart disease seemed capable of leading normal lives and seemed motivated to make good use of their abilities.

Prognosis after aortic valve replacement with a bioprosthesis: predictions based on meta-analysis and microsimulation

BackgroundBioprostheses are widely used as an aortic valve substitute, but knowledge about prognosis is still incomplete. The purpose of this study was to provide insight into the age-related life expectancy and actual risks of reoperation and valve-related events of patients after aortic valve replacement with a porcine bioprosthesis. Methods and ResultsWe conducted a meta-analysis of 9 selected reports on stented porcine bioprostheses, including 5837 patients with a total follow-up of 31 874 patient-years. The annual rates of valve thrombosis, thromboembolism, hemorrhage, and nonstructural dysfunction were 0.03%, 0.87%, 0.38%, and 0.38%, respectively. The annual rate of endocarditis was estimated at 0.68% for >6 months of implantation and was 5 times as high during the first 6 months. Structural valve deterioration was described with a Weibull model that incorporated lower risks for older patients. These estimates were used to parameterize, calibrate, and validate a mathematical microsimulation model. The model was used to predict life expectancy and actual risks of reoperation and valve-related events after implantation for patients of different ages. For a 65-year-old male, these figures were 11.3 years, 28%, and 47%, respectively. ConclusionsThe combination of meta-analysis with microsimulation enabled a detailed insight into the prognosis after aortic valve replacement with a bioprosthesis for patients of different ages. This information will be useful for patient counseling and clinical decision making. It also could serve as a baseline for the evaluation of newer valve types.

Patient outcome after aortic valve replacement with a mechanical or biological prosthesis: Weighing lifetime anticoagulant-related event risk against reoperation risk

OBJECTIVE Although the results of aortic valve replacement with different valve prostheses are well documented in terms of survival, the risks of (valve-related) events are less well explored. METHODS We used a dataset of 3934 patients who underwent aortic valve replacement with either a bioprosthesis (73%) or a mechanical prosthesis (27%) between 1982 and 2003 to simulate the outcome of patients after aortic valve replacement with either valve type. With the use of microsimulation, we compared total age and gender-specific life expectancy, event-free life expectancy, reoperation-free life expectancy, lifetime risks of reoperation, and valve-related events for both valve types. RESULTS The total follow-up was 26,467 patient-years. The mean follow-up was 6.1 years in the biological arm and 8.5 years in the mechanical arm. The mean age at implantation was 70 and 58 years for biological and mechanical prostheses, respectively, and the percentage of concomitant coronary artery bypass grafting was 47% and 28%, respectively. For a 60-year-old man, simulated life expectancy in years for biological versus mechanical prostheses was 11.9 versus 12.2, event-free life expectancy was 9.8 versus 9.3, and reoperation-free life expectancy was 10.5 versus 11.9. Lifetime risk of reoperation was 25% versus 3%. Lifetime risk of bleeding was 12% versus 41%. CONCLUSION Even for patients aged 60 years, event-free life expectancy is better with a bioprosthesis. Although the chance of reoperation is higher, the lifetime risk of bleeding is lower compared with a mechanical prosthesis. Comparing lifetime event risks between different types of valve prostheses provides more insight into patient outcome after aortic valve replacement and aids patient selection and counseling.