Non-rheumatic Valvular Disease Research Articles

Increased risk of stroke in non-rheumatic valvular disease associated with antiphospholipid syndrome (APS): a US nationwide study 2017-2019

Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune syndrome characterized by the presence of antiphospholipid autoantibodies, arterial and venous thrombosis, recurrent pregnancy loss and thrombocytopenia. Cardiac manifestations are also common which include coronary artery disease (CAD), non rheumatic valvular heart disorders (NRVHD), myocardial dysfunction, intracardiac thrombi and pulmonary hypertension. Valvular lesions occur likely due to immune complex deposition on the valves, causing fibrosis, calcification and subsequently valvular deformities. Literature review suggests prevalence of NRVHD in APS population is 30% and left sided valves are more involved than right. An increased risk of stroke has also been seen in APS patients with valvular disorders. Purpose Studies report variations in incidence of NRVHD in association with APS. To estimate the prevalence of NRVHD and their correlation with APS, we conducted a retrospective database analysis of hospitalizations across the United States. Additionally we investigated whether this association indicates a increased risk of ischemic stroke in this specific subpopulation. Methods The national inpatient sample (NIS) from 2017-2019 was queried for adult patients (age>18 yrs) admitted with a primary or secondary diagnosis of APS. These patients were stratified for different NRVHD including tricuspid stenosis, tricuspid insufficiency, pulmonary stenosis, pulmonary regurgitation, mitral stenosis, mitral insufficiency (MI), aortic stenosis (AS), and aortic regurgitation. Baseline risk factors and cardiac complications were compared. Multiple regression analysis was performed to study the association of NRVHD with stroke as the primary outcome in the subpopulation of APS hospitalizations. Results A total of 567600 adult patients hospitalized with diagnosis of APS were identified from the NIS 2017-2019 database. Among those, 33,095 had NRVHD with a mean age of 69 years. Of these, prevalence of males was 52.41% compared to females of 47.59%. In the cohort of APS, patients with NRVHD had a higher prevalence of coronary artery disease (43.78% vs 20.41%), diabetes mellitus (30.65% vs 27.56%), prior stroke (10.42% vs 7.78%) than those without valvular disorders. Among the APS population the most prevalent NRVHD were mitral insufficiency (MI), 2.45% and aortic stenosis (AS), 2.13%. In the cohort of NRVHD in APS hospitalizations, the odds of stroke was found to be 1.3 times higher with statistical significance (confidence interval (CI): 1.13-1.48, p <0.001) adjusted for relevant clinical and demographic risk factors such as tobacco abuse, CAD, diabetes mellitus, prior stroke. Conclusion This study shows 6.2% prevalence of NRVHD in APS population, of which MI and AS were common. NRVHD is also associated with higher odds of stroke in APS. Further studies are warranted in identifying the risk of stroke with NRVHD in APS population and emphasizing the need for early detection.

Abstract 16267: Burden of Cardiovascular Disease in Sub-Saharan Africa

Introduction: This study aims to explore the burden of cardiovascular disease (CVD) and associated risk factors in Sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD). Hypothesis: That the burden of CVD has increased in SSA over time, and there are associated risk factors contributing to this burden. Methods: We analyzed CVD prevalence, mortality, and incidence in 46 SSA countries using Bayesian regression, demographic methodologies, and mortality-to-incidence ratios. Disability-adjusted life years (DALYs) were calculated, and risk factors were assessed through the comparative risk assessment framework of the GBD. Results: Between 1990 and 2019, CVD prevalence in SSA increased by 131.7%, with a modest rise of 2.1% in age-standardized prevalence rates. Ischemic heart disease, stroke (CVA), and rheumatic heart disease were the most prevalent conditions. CVD deaths increased from 564,140 to 1,003,893, with a 14.4% decrease in death rates. Non-rheumatic valvular disease showed a significant increase. DALYs increased by 68.4%, but some CVDs saw decreases in DALY rates. Conclusions: Despite rising CVD prevalence in SSA, age-standardized rates only modestly increased. However, the persistently high burden, increasing non-rheumatic valvular disease, and rising DALYs highlight challenges in prevention and management. These findings highlight the persistent challenge of CVD in SSA and emphasize the need for continued efforts in prevention and management strategies to address the growing burden of CVD in this region.

Valvular heart diseases in immigrants and Swedish-born individuals: a national cohort study

Objectives. The aim of this study was to analyse the risk of valvular heart diseases among foreign-born individuals in Sweden. Design. This was a nationwide study of individuals aged 18 years of age and older (N = 6,118,649; 2,970,055 men and 3,148,594 women). Valvular heart diseases were defined as at least one registered diagnosis in the National Patient Register between 1 January 1998 and 31 December 2012. Cox regression analysis was used to estimate hazard ratios (HR) with 99% confidence intervals (CI) of incident valvular heart diseases in foreign-born individuals compared to Swedish natives. The Cox regression models were adjusted for age, co-morbidities, and sociodemographic factors. Sub-categories were chronic rheumatic valvular heart diseases and non-rheumatic valvular heart diseases. Results. There were 64,979 male cases and 59,075 female cases. Fully adjusted HRs (99% CI) were among immigrant men 0.86 (0.82–0.89) and immigrant women 0.96 (0.92–1.00). For chronic rheumatic valvular disease among immigrant men and women, the HRs were 1.62 (1.37–1.92) and 1.75 (1.52–2.00), respectively, and, for non-rheumatic valvular disease among immigrant men 0.83 (0.80–0.87) and immigrant women 0.92 (0.88–0.96). Increased risks for chronic rheumatic valvular disease were found among men from Southern, Eastern and Central Europe, Africa and Asia and among women from Western, Eastern and Central Europe and Africa, Latin America and Asia. Conclusions. We observed lower risks in general of valvular heart disease, but higher risks of chronic rheumatic valvular heart disease in immigrants, which is important in the clinical situation.

Development and Evaluation of a Prediction Model for Ascertaining Rheumatic Heart Disease Status in Administrative Data.

BackgroundPrevious research has raised substantial concerns regarding the validity of the International Statistical Classification of Diseases and Related Health Problems (ICD) codes (ICD-10 I05–I09) for rheumatic heart disease (RHD) due to likely misclassification of non-rheumatic valvular disease (non-rheumatic VHD) as RHD. There is currently no validated, quantitative approach for reliable case ascertainment of RHD in administrative hospital data.MethodsA comprehensive dataset of validated Australian RHD cases was compiled and linked to inpatient hospital records with an RHD ICD code (2000–2018, n=7555). A prediction model was developed based on a generalized linear mixed model structure considering an extensive range of demographic and clinical variables. It was validated internally using randomly selected cross-validation samples and externally. Conditional optimal probability cutpoints were calculated, maximising discrimination separately for high-risk versus low-risk populations.ResultsThe proposed model reduced the false-positive rate (FPR) from acute rheumatic fever (ARF) cases misclassified as RHD from 0.59 to 0.27; similarly for non-rheumatic VHD from 0.77 to 0.22. Overall, the model achieved strong discriminant capacity (AUC: 0.93) and maintained a similar robust performance during external validation (AUC: 0.88). It can also be used when only basic demographic and diagnosis data are available.ConclusionThis paper is the first to show that not only misclassification of non-rheumatic VHD but also of ARF as RHD yields substantial FPRs. Both sources of bias can be successfully addressed with the proposed model which provides an effective solution for reliable RHD case ascertainment from hospital data for epidemiological disease monitoring and policy evaluation.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Cardiovascular Disease in Relation to Placental Abruption: APopulation-Based Cohort Study from Denmark.

Cardiovascular (CVD) complications stemming from vascular dysfunction have been widely explored in the setting of preeclampsia. However, the impact of abruption, a strong indicator of microvascular disturbance, on the risk of CVD mortality and morbidity remains poorly characterised. We designed a cohort analysis of 828289 women who delivered singletons in Denmark between 1978 and 2010. We linked the National Patient Registry and the Registry of Causes of Death to the Danish Birth Registry to ascertain CVD events. We estimated CVD risks in relation to abruption from Cox proportional hazards regression following adjustments for confounders. With 13231562 person-years of follow-up of women with at least one delivery, 11829 pregnancies were complicated by abruption. The median (interquartile range) follow-up in the non-abruption and abruption groups was 16 (8, 24) and 18 (10, 25) years, respectively. CVD mortality rates in women with and without abruption were 0.9 and 0.3 per 10000 person-years, respectively (adjusted hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.5, 5.0). The corresponding CVD morbidity complication rates were 16.7 and 10.0 per 10000 person-years, respectively (HR 1.5, 95% CI 1.4, 1.8). The increased risks were evident for ischaemic heart disease, acute myocardial infarction, hypertensive heart disease, non-rheumatic valvular disease, and congestive heart failure. This study shows increased hazards of CVD morbidity and mortality in relation to abruption. A better understanding of the pathogenesis of distorted placental microvasculature is needed as this appears to be a harbinger of CVD later in life.

Heart Valve Lesions Due to the Formation of a Beta-Hemolytic Streptococ Role of Adhesion Molecules

Objectives: A rise in the levels of adhesion molecules such as VCAM-1, ICAM-1and E-selectin in valve disease patients has been reported lately. In our study, by detecting the presence of adhesion molecule expression in the valve endothelium we will try to show the level of adhesion molecules in peripheral blood leucocytes. Materials and Methods: Valve samples were obtained from patients having undergone aortic and mitral valve replacement due to symptomatic aortic stenosis/aortic insufficiency and/or mitral stenosis/mitral insufficiency. The clinical preoperative diagnosis was made using two-dimensional echocardiography and Doppler echocardiography. Rheumatic valves were in group B (n = 20). Group A (n = 8) constituted the control group. Immunohistochemical staining was performed using CD4, CD8, CD54/ICAM-1, and CD106/VCAM-1. Flow cytometric analysis was performed. The Kolmogorov-Smirnov test and Fisher’s exact test were used for the comparison of categorical variables. Results: Group A (non-rheumatic) patients were found to be older than group B (rheumatic) patients (59.8 ± 11.4 years vs. 45.3 ± 11.8 years, p = 0.008). In group B VCAM-1 level was higher than that of group A (296.6 ± 21.2 vs. 258.5 ± 42.1, p = 0.004). CD11b monocyte in group B was higher than in group A (98.8 ± 0.5 vs. 92.9 ± 9.7, p = 0.003). CD11b granulocyte was higher in group B than in group A (99.96 ± 0.05 vs. 93.79 ± 13.26, p = 0.33). Significant differences were not determined in the other parameters. Conclusion: The fact that increases in serum VCAM-1 and CD-11b only occurred in patients with rheumatic valvular disease in our study suggests that inflammation in patients with the same hemodynamic disorder is higher in rheumatic valvular disease than in the ones with non-rheumatic valvular disease.

Neurología y cardiología: puntos de contacto

Strokes resulting from cardiac diseases, and cardiac abnormalities associated with neuromuscular disorders are examples of the many points of contact between neurology and cardiology. Approximately 20-30% of strokes are related to cardiac diseases, including atrial fibrillation, congestive heart failure, bacterial endocarditis, rheumatic and nonrheumatic valvular diseases, acute myocardial infarction with left ventricular thrombus, and cardiomyopathies associated with muscular dystrophies, among others. Strokes can also occur in the setting of cardiac interventions such as cardiac catheterization and coronary artery bypass procedures. Treatment to prevent recurrent stroke in any of these settings depends on the underlying etiology. Whereas anticoagulation with vitamin K antagonists is proven to be superior to acetylsalicylic acid for stroke prevention in atrial fibrillation, the superiority of anticoagulants has not been conclusively established for stroke associated with congestive heart failure and is contraindicated in those with infective endocarditis. Ongoing trials are evaluating management strategies in patients with atrial level shunts due to patent foramen ovale. Cardiomyopathies and conduction abnormalities are part of the spectrum of many neuromuscular disorders including mitochondrial disorders and muscular dystrophies. Cardiologists and neurologists share responsibility for caring for patients with or at risk for cardiogenic strokes, and for screening and managing the heart disease associated with neuromuscular disorders. Full English text available from: www.revespcardiol.org

Neurology and Cardiology: Points of Contact

Strokes resulting from cardiac diseases, and cardiac abnormalities associated with neuromuscular disorders are examples of the many points of contact between neurology and cardiology. Approximately 20%-30% of strokes are related to cardiac diseases, including atrial fibrillation, congestive heart failure, bacterial endocarditis, rheumatic and nonrheumatic valvular diseases, acute myocardial infarction with left ventricular thrombus, and cardiomyopathies associated with muscular dystrophies, among others. Strokes can also occur in the setting of cardiac interventions such as cardiac catheterization and coronary artery bypass procedures. Treatment to prevent recurrent stroke in any of these settings depends on the underlying etiology. Whereas anticoagulation with vitamin K antagonists is proven to be superior to acetylsalicylic acid for stroke prevention in atrial fibrillation, the superiority of anticoagulants has not been conclusively established for stroke associated with congestive heart failure and is contraindicated in those with infective endocarditis. Ongoing trials are evaluating management strategies in patients with atrial level shunts due to patent foramen ovale. Cardiomyopathies and conduction abnormalities are part of the spectrum of many neuromuscular disorders including mitochondrial disorders and muscular dystrophies. Cardiologists and neurologists share responsibility for caring for patients with or at risk for cardiogenic strokes, and for screening and managing the heart disease associated with neuromuscular disorders.

Underutilization of anticoagulation therapy in chronic atrial fibrillation.

Atrial fibrillation, the most common chronic arrhythmia, results in an increased risk of stroke. Anticoagulation therapy can reduce this risk, but appears to be underused. The objective of this study was to examine the use of warfarin and prevalence of stroke in patients with rheumatic, nonrheumatic valvular and nonvalvular atrial fibrillation. Between January 1993 and December 1998, 457 chronic atrial fibrillation patients with continuous follow-up in our hospital were identified as having rheumatic heart disease (n = 114): nonrheumatic valvular disease (n = 65); or nonvalvular disease (n = 278). Warfarin was used less often in patients with nonrheumatic valvular (16.7%) and nonvalvular diseases (20.1%) than in those with rheumatic heart disease (81.6%, p < 0.001). In contrast, the prevalence of stroke among patients with nonvalvular disease was 40.3% which was similar to the 33.3% found in patients with rheumatic heart disease but significantly higher than the 24.6% found in patients with nonrheumatic valvular disease (p < 0.05). A history of stroke did not alter the trend of use of warfarin among the three groups of patients. Only 20.6% of patients on warfarin received monthly monitoring of prothrombin time. In conclusion, the anticoagulation therapy in our patients with chronic atrial fibrillation, regardless of their associated valvular diseases, is significantly underutilized. This underuse could account for a high prevalence of stroke. This risk of stroke, however, is less in patients with nonrheumatic valvular discase than in those with nonvalvular atrial fibrillation.

Comparative study between valve repair and replacement for mitral pure regurgitation. Early and late postoperative results.

From May 1975 through December 1988, 91 patients (mean age 50.4 +/- 12.8 years) had first-time surgery for mitral pure regurgitation; 48 had mitral valve replacement (MVR) and 43 had valve repair. A majority of the patients had non-rheumatic valvular diseases. Those patients who underwent repair had less hemodynamic and functional derangement than those who underwent MVR. The operative mortality was 8.3% in the MVR group and 2.3% in the repair group. Seventeen percent of the MVR group and 2% of the repair group required intra-aortic balloon pumping support (p less than 0.03). A higher dose of dopamine and/or dobutamine during the early postoperative period was necessary in the MVR group (7.0 +/- 4.8 micrograms/kg/min) than in the repair group (5.1 +/- 3.1 micrograms/kg/min). Duration of respirator support for hospital survivors was longer in the MVR group (2.3 +/- 2.7 days) than in the repair group (1.4 +/- 1.0 days). There were 5 late deaths (2.2 +/- 1.0%/pt-yr) not counting 6 non-cardiac deaths in the MVR group and 1 (0.6 +/- 0.6%/pt-yr) in the repair group. There were 17 patients (7.5 +/- 1.8%/pt-yr) who experienced treatment failure in the MVR group and 5 (2.3 +/- 1.3%/pt-yr) in the repair group (p less than 0.02). Eight patients in the MVR group (3.5 +/- 1.3%/pt-yr) underwent repeat surgery in the late postoperative period, as did 3 (1.7 +/- 1.0%/pt-yr) in the repair group. There was no increase in the incidence of repeat surgery after valve repair. All the current survivors in the repair group, and 96% of those in the MVR group were in NYHA functional class I or II. These results indicate that mitral repair is the preferred operative procedure for pure mitral regurgitation, whenever it is possible.

Myxomatous Transformation of Cardiac Valves : Non-rheumatic valvular diseases and their surgical treatment : PROCEEDINGS OF THE I. CONFERENCE ON PREVENTION FOR RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE

Two non-rheumatic valvular lesions in which myxomatous degeneration appears to be the genetic or relating factor are described. Floppy valve syndrome of the mitral valve occurs not infrequently in the childhood as well as in the older age, and it should be emphasized that this lesion encountered in the childhood must be carefully differentiated from the rheumatic heart disease. This condition might deteriorate rapidly and bring severe congestive heart failure, eventually with tricuspid insufficiency in spite of intensive medical treatment. The choice of surgical treatment for severe mitral insufficiency is mitral valve replacemnt even in the childhood. Mucoid degeneration is histologically revealed in the aortic valve of patients of ventricular septal defect associated with aortic insufficiency, too. The etiology of aortic insufficiency in this condition previously has been explained to be lace of support structure of the aortic valve.4 However, the facts that there may be even an infant associated with severe aortic insufficiency and the aortic valve specimen demonstrates an above-mentioned characteristic feature, would suggest that this condition may be caused by a certain congenital tissue anomaly.