M. Mostafa Mokhles

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.

Survival Comparison of the Ross Procedure and Mechanical Valve Replacement With Optimal Self-Management Anticoagulation Therapy Propensity-Matched Cohort Study

Background— It is suggested that in young adults the Ross procedure results in better late patient survival compared with mechanical prosthesis implantation. We performed a propensity score-matched study that assessed late survival in young adult patients after a Ross procedure versus that after mechanical aortic valve replacement with optimal self-management anticoagulation therapy. Methods and Results— We selected 918 Ross patients and 406 mechanical valve patients 18 to 60 years of age without dissection, aneurysm, or mitral valve replacement who survived an elective procedure (1994 to 2008). With the use of propensity score matching, late survival was compared between the 2 groups. Two hundred fifty-three patients with a mechanical valve (mean follow-up, 6.3 years) could be propensity matched to a Ross patient (mean follow-up, 5.1 years). Mean age of the matched cohort was 47.3 years in the Ross procedure group and 48.0 years in the mechanical valve group (P=0.17); the ratio of male to female patients was 3.2 in the Ross procedure group and 2.7 in the mechanical valve group (P=0.46). Linearized all-cause mortality rate was 0.53% per patient-year in the Ross procedure group compared with 0.30% per patient-year in the mechanical valve group (matched hazard ratio, 1.86; 95% confidence interval, 0.58 to 5.91; P=0.32). Late survival was comparable to that of the general German population. Conclusions— In comparable patients, there is no late survival difference in the first postoperative decade between the Ross procedure and mechanical aortic valve implantation with optimal anticoagulation self-management. Survival in these selected young adult patients closely resembles that of the general population, possibly as a result of highly specialized anticoagulation self-management, better timing of surgery, and improved patient selection in recent years.

Risk of cardiac valve regurgitation with dopamine agonist use in Parkinson's disease and hyperprolactinaemia: a multi-country, nested case-control study

AbstractBackground: There is growing evidence that ergot dopamine agonists may induce cardiac valve regurgitation (CVR) in persons with Parkinson’s disease. It is unclear whether the CVR risk is increased with ergot-dopamine agonist use in persons with hyperprolactinaemia, in whom the dose is much lower. Objective: The aim of the study was to explore the association between different dopamine agonists and CVR in patients with Parkinson’s disease or hyperprolactinaemia. Design: Nested case-control studies conducted separately in cohorts of Parkinson’s disease and hyperprolactinaemia patients. Cases were patients who developed newly diagnosed CVR. Controls were CVR-free patients from the same cohorts and were matched to cases by age, sex, database and calendar year. Setting and Patients: Study patients were identified from over 4.5 million persons in The Health Improvement Network (THIN; UK), Health Search (Italy), and Integrated Primary Care Information (IPCI; the Netherlands) general practice databases in the years 1996–2007. The Parkinson’s disease cohort included new users of dopamine agonists or levodopa, while the hyperprolactinaemia cohort included new users or non-users of dopamine agonists. Main Outcome Measure: Risk of newly diagnosed CVR with dopamine agonist use compared with levodopa use in the Parkinson’s disease cohort, and dopamine agonist-naïve patients in the hyperprolactinaemia cohort. Results: In the Parkinson’s disease cohort (7893 dopamine agonist users, 11 766 levodopa users), 85 incident CVR cases were identified. Increased CVR risk was observed for ergot dopamine agonists (adjusted OR [ORadj] 3.82; 95% CI 2.14, 6.81), but not for non-ergot dopamine agonists (ORadj 1.20; 95% CI 0.63, 2.29).In the hyperprolactinaemia cohort (6740 dopamine agonist users and 14299 dopamine agonist-naïve patients), 37 CVR cases were identified during a mean follow-up of 4.5 years and 3.5 years for new users and non-users of dopamine agonists, respectively. However, no association with ever use of ergot dopamine agonists was observed (ORadj 0.47; 95% CI 0.20,1.19). Conclusion: Ergot-derived dopamine agonists are associated with an increased risk of CVR in Parkinson’s disease but not in hyperprolactinaemia patients.

Autograft and pulmonary allograft performance in the second post-operative decade after the Ross procedure: insights from the Rotterdam Prospective Cohort Study

AIMS The objective of the present study was to report our ongoing prospective cohort of autograft recipients with up to 21 years of follow-up. METHODS AND RESULTS All consecutive patients (n = 161), operated between 1988 and 2010, were analysed. Mixed-effects models were used to assess changes in echocardiographic measurements (n = 1023) over time in both the autograft and the pulmonary allograft. The mean patient age was 20.9 years (range 0.05-52.7)-66.5% were male. Early mortality was 2.5% (n = 4), and eight additional patients died during a mean follow-up of 11.6 ± 5.7 years (range 0-21.5). Patient survival was 90% [95% confidence interval (CI), 78-95] up to 18 years. During the follow-up, 57 patients required a re-intervention related to the Ross operation. Freedom from autograft reoperation and allograft re-intervention was 51% (95% CI 38-63) and 82% (95% CI 71-89) after 18 years, respectively. No major changes were observed over time in autograft gradient, and allograft gradient and regurgitation. An initial increase of sinotubular junction and aortic anulus diameter was observed in the first 5 years after surgery. The only factor associated with an increased autograft reoperation rate was pre-operative pure aortic regurgitation (AR) (hazard ratio 1.88; 95% CI 1.04-3.39; P= 0.037). CONCLUSION We observed good late survival in patients undergoing autograft procedure without reinforcement techniques. However, over half of the autografts failed prior to the end of the second decade. The reoperation rate and the results of echocardiographic measurements over time underline the importance of careful monitoring especially in the second decade after the initial autograft operation and in particular in patients with pre-operative AR.

Comparison of clinical outcome of stage I non-small cell lung cancer treated surgically or with stereotactic radiotherapy: Results from propensity score analysis

OBJECTIVES Guideline-specified curative therapies for a clinical stage I non-small cell lung cancer (NSCLC) are either lobectomy or Stereotactic Ablative Radiotherapy (SABR). As outcomes of prospective randomized clinical trials comparing these modalities are unavailable, we performed a propensity-score matched analysis to create two similar groups in order to compare clinical outcomes. METHODS We selected 577 patients, 96 VATS or open lobectomy were treated at Erasmus University Medical Center Rotterdam and 481 SABR patients were treated at VU University Medical Center Amsterdam with clinical stage I NSCLC. RESULTS Matching of patients according to propensity score resulted in a cohort that consisted of 73 patients in the surgery group and of 73 patients in the SABR group. Median follow-up in the surgery and SABR group was 49 months and 28 months, respectively. Overall survival of patients who underwent surgery was 95% and 80% at 12 and 60 months, respectively. For the SABR group this was 94% at 12 months and 53% at 60 months. No statistical significant difference (p=0.089) in survival was found between these groups. CONCLUSIONS In this study we found no significant differences in overall survival in propensity matched patients diagnosed with stage I NSCLC treated either surgically or with SABR. After 3 years there seems to be a trend toward improved survival in patients who were treated surgically.

The risk of new onset heart failure associated with dopamine agonist use in Parkinson's disease.

The aim of present study was to investigate the risk of heart failure associated with dopamine agonist use in patients with Parkinsons disease. The data sources of this study were four different population-based, healthcare databases in United Kingdom, Italy and Netherlands. A case control study nested within a cohort of Parkinsons disease patients who were new users of either dopamine agonist or levodopa was conducted. Incident cases of heart failure were identified and validated, using Framingham criteria. Controls were matched to cases on age, gender and database. To estimate the risk of newly diagnosed heart failure with ergot and non-ergot derived dopamine agonists, as compared to levodopa, odds ratios and 95% confidence intervals were calculated through conditional logistic regression. In the cohort of 25,459 Parkinsons disease patients (11,151 new users of dopamine agonists, 14,308 new users of levodopa), 518 incident heart failure cases were identified during follow-up. Compared to levodopa, no increased risk of heart failure was found for ergot dopamine agonists (odds ratio: 1.03; 95% confidence interval: 0.69-1.55). Among non-ergot dopamine agonists, only pramipexole was associated with an increased risk of heart failure (odds ratio: 1.61; 95%confidence interval: 1.09-2.38), especially in the first three months of therapy (odds ratio: 3.06; 95% confidence interval: 1.74-5.39) and in patients aged 80 years and older (odds ratio: 3.30; 95% confidence interval: 1.62-7.13). The results of this study indicate that ergot dopamine agonist use in Parkinsons disease patients was not associated with an increased risk of newly diagnosed heart failure. Among non-ergot dopamine agonists, we observed a statistically significant association between pramipexole use and heart failure, especially during the first months of therapy and in very old patients.

Survival of surgically treated infective endocarditis: A comparison with the general dutch population

BACKGROUND Infective endocarditis (IE) remains associated with high in-hospital and long-term mortality. The outcome of patients with IE who are operated on has never been put into perspective by comparing it to the age-matched and gender-matched general population. The aim of the present study was to evaluate the long-term mortality of patients with IE who undergo operation in relation to the age-matched and gender-matched general population. METHODS A retrospective observational cohort study of 138 patients with IE who underwent consecutive operations (1998-2007) was conducted. Cumulative survival was analyzed using the Kaplan-Meier method. Comparison of patient survival with the general population was done using the Dutch population life table. The standardized mortality ratio was used to assess the degree of late deaths. RESULTS The observed in-hospital mortality risk was 10.9%. The observed long-term survival was 85% (95% confidence interval, 78% to 90%), 74% (95% confidence interval, 65% to 79%), 71% (95% confidence interval, 62% to 78%) after 1, 5, and 10 years, respectively. Age-matched and gender-matched survival in the general population was 99%, 93%, and 80% after a follow-up period of 1, 5, and 10 years, respectively. The standardized mortality ratio was 0.99 (95% confidence interval, 0.67 to 1.31). CONCLUSIONS Although mortality of IE patients who have undergone operation remains considerable during the immediate postoperative period, the mortality of hospital survivors is, with increasing follow-up time, comparable with the general population.

The Ross procedure using autologous support of the pulmonary autograft: techniques and late results

OBJECTIVES It is hypothesized that by performing radical aortic root manipulation and then autologous support for the pulmonary autograft in the Ross procedure, this will maintain aortic root size and should, in turn, lead to the demonstrated low incidence of late aortic regurgitation and need for reoperation on the aortic root and valve. METHODS Aortic root size was measured echocardiographically both preoperatively and then at second yearly intervals in 322 consecutive patients who underwent a Ross operation between October 1992 and June 2013 with autologous support of the pulmonary autograft root using the patients own aorta. This technique, a variant of the inclusion cylinder method, has been developed with the aim of minimizing prosthetic materials in the aortic root. RESULTS Measures to reduce aortic root size included annulus reduction in 201 patients (62.4%) and reduction in aortic sinus or sinotubular junction in 159 patients (49.4%). Maximal aortic root diameter postoperatively at 5, 10, and 15 years was 34.0, 34.6, and 34.7 mm, respectively. Eleven reoperations were required during the study period for progressive aortic regurgitation (none for aortic root enlargement), with freedom from reoperation being 96% at both 15 years and 18 years. Preoperative pure aortic regurgitation, aortic annulus, and sinotubular junction enlargement were risk factors for reoperation. CONCLUSIONS This inclusion method of pulmonary autograft implantation leads to minimal increases in aortic root size over time, with no reoperations for aortic root dilatation and a low requirement for aortic valve reoperation. The Ross procedure deserves to remain on the surgical menu for aortic valve replacement.

Twenty-year analysis of autologous support of the pulmonary autograft in the ross procedure

BACKGROUND The Ross procedure is seldom offered to adults less than 60 years of age who require aortic valve replacement except in a few high-volume centers with documented expertise. Inserting the pulmonary autograft as an unsupported root replacement may lead to increasing reoperations on the aortic valve in the second decade. METHODS Of 333 patients undergoing the Ross procedure between October 1992 and June 2012, the study group of 310 consecutive patients (mean age ± standard deviation, 39.3±12.7 years (limits 16-63) had the aortic root size adjusted to match the pulmonary autograft, which was inserted as a root replacement, with the aorta closed up around it to provide autologous support. RESULTS The mean follow-up time was 9.4 years; the actuarial survival was 97% at 16 years; and freedom from the composite of all reoperations on the aortic valve and late echocardiographic-detected aortic regurgitation greater than mild was 95% at 5 years, 94% at 10 years, and 93% at 15 years. Overall freedom from all reoperations on aortic and pulmonary valves was 97% at 5 years, 94% at 10 years, and 93% at 15 years. All results were better for the patients presenting with predominant aortic stenosis (98% freedom at 15 years) than for those with aortic regurgitation (p=0.01). CONCLUSIONS Autologous support of the pulmonary autograft leads to excellent results in the groups presenting with aortic stenosis and mixed aortic stenosis/regurgitation and to good results for those presenting with pure aortic regurgitation. The Ross procedure, using one of the proven, durable techniques available, should be considered for more widespread adoption.

Surgery in current therapy for infective endocarditis

The introduction of the Duke criteria and transesophageal echocardiography has improved early recognition of infective endocarditis but patients are still at high risk for severe morbidity or death. Whether an exclusively antibiotic regimen is superior to surgical intervention is subject to ongoing debate. Current guidelines indicate when surgery is the preferred treatment, but decisions are often based on physician preferences. Surgery has shown to decrease the risk of short-term mortality in patients who present with specific symptoms or microorganisms; nevertheless even then it often remains unclear when surgery should be performed. In this review we i) systematically reviewed the current literature comparing medical to surgical therapy to evaluate if surgery is the preferred option, ii) performed a meta-analysis of studies reporting propensity matched analyses, and iii), briefly summarized the current indications for surgery.