Cause Of Valvular Heart Disease Research Articles

Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis.

Rheumatic heart disease is the major cause of valvular heart disease in developing nations. Endothelial cells (ECs) are considered crucial contributors to rheumatic heart disease, but greater insight into their roles in disease progression is needed. We used a Cdh5-driven EC lineage-tracing approach to identify and track ECs in the K/B.g7 model of autoimmune valvular carditis. Single-cell RNA sequencing was used to characterize the EC populations in control and inflamed mitral valves. Immunostaining and conventional histology were used to evaluate lineage tracing and validate single-cell RNA-sequencing findings. The effects of VEGFR3 (vascular endothelial growth factor receptor 3) and VEGF-C (vascular endothelial growth factor C) inhibitors were tested in vivo. The functional impact of mitral valve disease in the K/B.g7 mouse was evaluated using echocardiography. Finally, to translate our findings, we analyzed valves from human patients with rheumatic heart disease undergoing mitral valve replacements. Lineage tracing in K/B.g7 mice revealed new capillary lymphatic vessels arising from valve surface ECs during the progression of disease in K/B.g7 mice. Unsupervised clustering of mitral valve single-cell RNA-sequencing data revealed novel lymphatic valve ECs that express a transcriptional profile distinct from other valve EC populations including the recently identified PROX1 (Prospero homeobox protein 1)+ lymphatic valve ECs. During disease progression, these newly identified lymphatic valve ECs expand and upregulate a profibrotic transcriptional profile. Inhibiting VEGFR3 through multiple approaches prevented expansion of this mitral valve lymphatic network. Echocardiography demonstrated that K/B.g7 mice have left ventricular dysfunction and mitral valve stenosis. Valve lymphatic density increased with age in K/B.g7 mice and correlated with worsened ventricular dysfunction. Importantly, human rheumatic valves contained similar lymphatics in greater numbers than nonrheumatic controls. These studies reveal a novel mode of inflammation-associated, VEGFR3-dependent postnatal lymphangiogenesis in murine autoimmune valvular carditis, with similarities to human rheumatic heart disease.

Transcatheter heart valve interventions for patients with rheumatic heart disease.

Rheumatic heart disease [RHD] is the most prevalent cause of valvular heart disease in the world, outstripping degenerative aortic stenosis numbers fourfold. Despite this, global resources are firmly aimed at improving the management of degenerative disease. Reasons remain complex and include lack of resources, expertise, and overall access to valve interventions in developing nations, where RHD is most prevalent. Is it time to consider less invasive alternatives to conventional valve surgery? Several anatomical and pathological differences exist between degenerative and rheumatic valves, including percutaneous valve landing zones. These are poorly documented and may require dedicated solutions when considering percutaneous intervention. Percutaneous balloon mitral valvuloplasty (PBMV) is the treatment of choice for severe mitral stenosis (MS) but is reserved for patients with suitable valve anatomy without significant mitral regurgitation (MR), the commonest lesion in RHD. Valvuloplasty also rarely offers a durable solution for patients with rheumatic aortic stenosis (AS) or aortic regurgitation (AR). MR and AR pose unique challenges to successful transcatheter valve implantation as landing zone calcification, so central in docking transcatheter aortic valves in degenerative AS, is often lacking. Surgery in young RHD patients requires mechanical prostheses for durability but morbidity and mortality from both thrombotic complications and bleeding on Warfarin remains excessively high. Also, redo surgery rates are high for progression of aortic valve disease in patients with prior mitral valve replacement (MVR). Transcatheter treatments may offer a solution to anticoagulation problems and address reoperation in patients with prior MVR or failing ventricles, but would have to be tailored to the rheumatic environment. The high prevalence of MR and AR, lack of calcification and other unique anatomical challenges remain. Improvements in tissue durability, the development of novel synthetic valve leaflet materials, dedicated delivery systems and docking stations or anchoring systems to securely land the transcatheter devices, would all require attention. We review the epidemiology of RHD and discuss anatomical differences between rheumatic valves and other pathologies with a view to transcatheter solutions. The shortcomings of current RHD management, including current transcatheter treatments, will be discussed and finally we look at future developments in the field.

Identification of distinct subgroups in moderately severe rheumatic mitral stenosis using data-driven phenotyping of longitudinal hemodynamic progression

Abstract Background Rheumatic mitral stenosis (MS) is a significant cause of valvular heart disease. Pulmonary artery systolic pressure (PASP) reflects the hemodynamic consequences of MS and is used to determine treatment strategies. However, PASP progression and expected outcomes in patients with moderately severe MS remain unclear. Purpose We aimed to examine the impact of progression rate of PASP in moderately severe MS. Methods A cohort of 866 consecutive patients with moderately severe rheumatic MS (1.0 cm2. Results Data-driven phenotyping identified two distinct trajectories based on PASP progression: a rapid progression group (N=38, 8.7%) and a slow progression group (N=398, 91.3%). Patients in the rapid progression group were older and had more comorbidities than patients in the slow progression group, including diabetes, and atrial fibrillation (all P<0.05). The initial mean diastolic pressure gradient and PASP were higher in the rapid progression group than in the slow progression group (6.2±2.4 mmHg vs. 5.1±2.0 mmHg, P=0.001, and 42.3±13.3 mmHg vs. 33.0±9.2 mmHg, P<0.001, respectively). During a mean follow-up of 7.0±3.0 years, the event-free survival rate was significantly lower in the rapid progression group than in the slow progression group (log-rank P<0.001). Rapid PASP progression was a significant risk factor for composite outcomes even after adjusting for comorbidities (hazard ratio: 3.08, 95% confidence interval (CI): 1.68–5.64, P<0.001). Multivariate regression analysis revealed that PASP>40 mmHg was independently associated with the probability of rapid progression group allocation (odds ratio: 4.95, 95% CI: 2.08–11.99, P<0.001). Conclusions Two groups with distinct patterns of PASP progression were identified. Rapid PASP progression was associated with a significantly higher risk of the composite outcomes. The main independent echocardiographic predictor for rapid progression group allocation was initial PASP>40 mmHg. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): This study was supported by a Severance Hospital Research fund for Clinical excellence (SHRC) (C-2020-0041) and a faculty research grant of Yonsei University College of Medicine (6-2020-0156).

Identification of Distinct Subgroups in Moderately Severe Rheumatic Mitral Stenosis Using Data-Driven Phenotyping of Longitudinal Hemodynamic Progression.

BackgroundRheumatic mitral stenosis is a significant cause of valvular heart disease. Pulmonary arterial systolic pressure (PASP) reflects the hemodynamic consequences of mitral stenosis and is used to determine treatment strategies. However, PASP progression and expected outcomes based on PASP changes in patients with moderately severe mitral stenosis remain unclear.Methods and ResultsA total of 436 patients with moderately severe rheumatic mitral stenosis (valve area 1.0–1.5 cm2) were enrolled. Composite outcomes included all‐cause mortality and hospitalization for heart failure. Data‐driven phenotyping identified 2 distinct trajectory groups based on PASP progression: rapid (8.7%) and slow (91.3%). Patients in the rapid progression group were older and had more diabetes and atrial fibrillation than those in the slow progression group (all P<0.05). The initial mean diastolic pressure gradient and PASP were higher in the rapid progression group than in the slow progression group (6.2±2.4 mm Hg versus 5.1±2.0 mm Hg [P=0.001] and 42.3±13.3 mm Hg versus 33.0±9.2 mm Hg [P<0.001], respectively). The rapid progression group had a poorer event‐free survival rate than the slow progression group (log‐rank P<0.001). Rapid PASP progression was a significant risk factor for composite outcomes even after adjusting for comorbidities (hazard ratio, 3.08 [95% CI, 1.68–5.64]; P<0.001). Multivariate regression analysis revealed that PASP >40 mm Hg was independently associated with allocation to the rapid progression group (odds ratio, 4.95 [95% CI, 2.08–11.99]; P<0.001).ConclusionsRapid PASP progression was associated with a higher risk of the composite outcomes. The main independent predictor for rapid progression group allocation was initial PASP >40 mm Hg.

Mortality and morbidity of surgical and transcatheter mitral valve repair in octogenarians: A systematic review.

Valvular heart disease (VHD) is a prominent problem in healthcare today with mitral regurgitation (MR) being the leading cause of VHD in the elderly population. While mitral valve repair (MVr) surgery isone of the only options for the end-stage disease, octogenarians are often denied MVr due to concerns with operative mortality and postoperative morbidity. To provide information on this underrepresented group of surgical patients, a systematic approach was taken to review the mortality and morbidity rates of octogenarians who received MVr. Pubmed and Medline were searched for articles containing outcomes of octogenarians receiving surgical mitral valve repair (SMVr) or transcatheter mitral valve repair (TMVr) published after 2000. Ten articles met the inclusion criteria for a total of 7968 patients included in the analysis using Microsoft Excel, Version 2105. Short-term mortality rates for SMVr and TMVr were 2.6% and 1.4% for in-hospital, and 7.8% and 3.3% for 30 days, respectively. The average incidence of stroke, acute kidney injury, infection, and major bleeding for SMVr were 3.2%, 11.2%, 7.7%, and 24%, respectively, and 0.3%, 6.7%, 2.7%, and 7.9% for TMVr, respectively. Octogenarians receiving SMVr or TMVr experienced similar rates of short-term mortality and morbidity as younger populations, and when considering life expectancy, midterm mortality was also similar. With these results, denying octogenarians MVr operations based on age alone should be reconsidered. Depending on risk factors and comorbidities, either SMVr or TMVr is a viable and relatively safe option for octogenarians with severe MR.

Cardiac valvular surgery and history of anorectic drug intake: A retrospective study of a large population of benfluorex-exposed patients

Anorectic drugs are overlooked as a cause of valvular heart disease (VHD). To describe the characteristics of a large population of patients with severe VHD who underwent cardiac surgery and had a history of benfluorex intake. Retrospective observational and cross-sectional study of patients from a large French database (Office National d'Indemnisation des Accidents Médicaux). Clinical, echocardiographic, surgical and pathology findings were comprehensively collected from medical files. From a chart review of 9584 subjects, 1031 patients with VHD underwent cardiac surgery; 453 surgical patients were excluded because of VHD obviously unrelated to benfluorex exposure, six because of missing data and eight declined to participate. The final study population comprised 564 patients who had surgery between 1987 and 2019. Median age was 58 (interquartile range 50-65) years; 85% were female. Median duration of preoperative benfluorex exposure was 5.8 (3.3-10) years. Most patients had aortic and mitral valve disease. Pure or predominant aortic and/or mitral regurgitation were found in 84% of patients (n=471), and aortic or mitral stenosis (pure or combined with regurgitation) in 12% (n=67) and 15% (n=84), respectively. Overall, 403 aortic, 402 mitral and 64 tricuspid valve surgical procedures were collected. Aortic and mitral valves were found to be thickened, rigid and/or restrictive in most cases; restrictive tricuspid valve disease was seldom documented. Pathology was available in half of the population (276 patients); valvular fibrosis suggestive of drug-induced VHD was found in 222 patients, including 146 with expert examination. Mixed VHD aetiologies were discussed in 107 patients, including 54 with available pathology. Drug-induced VHD features are miscellaneous, including well-known restrictive valvular regurgitation, but also stenosis or combined regurgitation and stenosis. Besides a history of drug taking, thorough echocardiography and comprehensive surgical reports, pathology is key in the diagnostic procedure.

Arrhythmic Mitral Valve Prolapse and Mitral Annular Disjunction: Clinical Features, Pathophysiology, Risk Stratification, and Management

Mitral valve prolapse (MVP) is a common cause of valvular heart disease. Although many patients with MVP have a benign course, there is increasing recognition of an arrhythmic phenotype associated with ventricular arrhythmias and sudden cardiac death (SCD). Pathophysiologic mechanisms associated with arrhythmias include cardiac fibrosis, mechanical stress induced changes in ventricular refractory periods, as well as electrophysiologic changes in Purkinje fibers. Clinically, a variety of risk factors including demographic, electrocardiographic, and imaging characteristics help to identify patients with MVP at the highest at risk of SCD and arrhythmias. Once identified, recent advances in treatment including device therapy, catheter ablation, and surgical interventions show promising outcomes. In this review, we will summarize the incidence of ventricular arrhythmias and SCD in patients with MVP, the association with mitral annular disjunction, mechanisms of arrhythmogenesis, methods for arrhythmic and SCD risk stratification including findings with multimodality imaging, and treatments for the primary and secondary prevention of SCD.

Incidence &amp; Pattern of Valvular Heart Disease in Patients attended in Echo Lab at a tertiary care Hospital: A single Centre Study

Background: This echocardiographic study was undertaken to establish incidence, pattern &amp; complications in patients of valvular heart disease.&#x0D; Methods: A total of 97 patients were enrolled among the patients attended in echo lab at Ibrahim cardiac hospital &amp; Research Institute over a period of 1 year.&#x0D; Results: Mean age was 53.8±1.5 years. Male were predominant (58.76% vs 41.23%). Most common symptom was shortness of breath (60.8%) followed by palpitation (43.3%). 39.2% of patients had normal ECG &amp; 12.4% revealed AF. The most common complication was pulmonary hypertension (54.6%) followed by pulmonary edema (26.8%), Stroke (10.3%), Left atrial thrombus (7.3%), &amp; infective endocarditis (6.2%). MV was most commonly involved (72.2%) followed by aortic valve (AV) (66.0%), tricuspid valve (TV) (54.6%) &amp; pulmonary valve (PV) was (20.6%). Rheumatic involvement (52.6%) constituted the dominant cause than degenerative &amp; congenital (24.7% in each). Mitral stenosis (MS) was predominant (52.6%) &amp; was rheumatic in origin; then aortic stenosis (AS) (48.5%) which was mostly degenerative followed by bicuspid aortic valve (8.2%). Mitral regurgitation (MR) was the most common valvular lesion (64.9%); then aortic regurgitation (AR) (51.5%) which was also rheumatic in etiology. Multiple valve involvement was also present. The most common variety was MS+MR (43.3%). Tricuspid stenosis (TS) was in association with MR+AR (1.03%). Tricuspid regurgitation (TR) was 58.8%, mostly secondary to rheumatic involvement of other valves. Severe TR (5.2%) was due to Ebstain anomaly and prolapse (4.1% &amp; 3.1%). ventricular systolic &amp; diastolic functions were normal mostly.&#x0D; Conclusion: Among the rheumatic heart disease patients’ mitral valve was the most commonly affected valve. Mitral regurgitation was the most common valvular lesion. Rheumatic involvement remains the dominant cause of valvular heart disease in Bangladesh.&#x0D; Cardiovasc. j. 2021; 13(2): 144-153

Outcome of Rheumatic Heart Disease and Percutaneous Balloon Mitral Valvotomy

Abstract Background: Rheumatic heart disease (RHD) is still a leading cause of valvular heart disease in India. Balloon mitral valvotomy (BMV) is simple and safe procedure to improve the quality of life in patients with severe mitral stenosis. Aim: (1) To evaluate outcome of RHD patients in tertiary care hospital in developing country like India in twenty first century. (2) To evaluate safety and efficacy of BMV. Materials and Methods: We performed retrospective analysis of 500 patients with RHD undergoing echocardiography in a tertiary care hospital in Maharashtra, India. 15% (74 patients) of them underwent balloon mitral valvuloplasty between June 2012 and November 2019 and 37.6% (188 patients) were treated with valve replacements. Results: Successful BMV was performed in 72 patients. The rate of complication was 2.7%. No mortality was noted. One hundred and eighty-eight patients underwent Valve replacements. Conclusions: Balloon mitral valvuloplasty is a technically difficult procedure and demands considerable expertise in transseptal catheterization. Percutaneous balloon mitral valvotomy is a safe and effective treatment for symptomatic severe Mitral stenosis in experienced centers.

Chapter 12 - Neurologic complications of nonbacterial thrombotic endocarditis

Endocarditis is an inflammatory or infective condition affecting the cardiac valves or endocardium, often associated with serious neurological sequelae. Nonbacterial thrombotic endocarditis (NBTE)-referred to as degenerative, Libman-Sachs, marantic, verrucous, or terminal endocarditis-is a serious but rare cause of valvular heart disease characterized by deposition of sterile vegetations of fibrin and platelet aggregates on the cardiac valves, eventually resulting in life-threatening embolization of these thrombi to the brain, limbs, or visceral organs. NBTE may complicate a heterogeneous group of chronic conditions, predominantly connective tissue and autoimmune disorders, malignancies, and diseases associated with hypercoagulability states. NBTE usually affects the native rather than prosthetic valves, and unlike infective endocarditis (IE), sparing the involved valve function without its destruction. Compared to those seen in IE, vegetations in NBTE are small and friable, thus may easily be dislodged leading to systemic thromboembolism with devastating morbidities and mortality. There are no diagnostic criteria for NBTE, and antemortem diagnosis is challenging. The condition should be suspected in patients with thromboembolic events and vegetations on the cardiac valves on echocardiographic or cardiac imaging studies, in the absence of underlying infection, especially in disorders predisposing to coagulopathy. Early recognition and prompt treatment of the primary underlying disorder is essential. Anticoagulation with heparin or heparinoid products is recommended to prevent recurrent embolism. Surgical intervention is not indicated except in selected patients with life-threatening recurrent embolism.

Prevalence of rheumatic fever/rheumatic heart disease among school children of age group 5-15 years in district Jammu

Introduction: Rheumatic fever and rheumatic heart disease are major cause of valvular heart disease in the world. It is estimated that up to 15.6 million people worldwide are affected by rheumatic heart disease and every year approximately 470,000 new cases are detected and 2,33,000 deaths are attributed to rheumatic heart disease. Objective: A study was conducted by department of Community medicine, Government Medical College Jammu (J&K) to assess the prevalence of rheumatic fever and rheumatic heart disease among school children in age group of 5-15 years, in Jammu district. Materials and Methods: A cross sectional study involving the screening of school children drawn from schools of Jammu district as a part of a research project of ICMR under Jai Vigyan Mission Mode (JVMM). Participants included ten thousand students of schools of Jammu district in ten age slots in age group of 5-15years, each having 1000 children. Setting: The schools were selected by stratified systematic random sampling technique such that half of children (5000) belonged to rural schools and half (5000) to urban schools with equal sex distribution as well as equal government private distribution. Study Period: May 2007 to March 2010. Results: Prevalence of rheumatic fever and rheumatic heart disease were found to be respectively 0.7/1000 and 0.6/ 1000 school children in age group 5-15 years. Conclusion: Keeping in view these results, the burden of rheumatic fever and rheumatic heart disease on the public health system for chemoprophylaxis and surgery cannot be ignored. Hence, although on a decline, but still rheumatic fever and rheumatic heart disease remain a public health problem for the young populations aged 05-15 years in this part of country. Keywords: Rheumatic fever, Rheumatic heart disease, Children 5-15 years, Jammu.

Epidemiology of surgical valvular heart diseases in a north african tertiary referral hospital

The etiology of valvular heart disease (VHD) has changed dramatically in the last five decades. In the western world, the significant reduction of acute rheumatic fever and its sequelae, and the recognition of non-rheumatic causes of VHD induced the metamorphosis in the etiology of valvular disorders. The aim of this study was to assess the epidemiological profile of the patients undergoing valvular surgery in a north African center of cardiology. A retrospective study involving the 246 last patients hospitalized in our department and proposed for valvular surgery from January 2012 to December 2017. The mean age was 57 years. One hundred twenty-one patients were male (49%). Before surgery mean LVEF is 60% ± 13. Ten percent of the patients were operated with (left ventricular dysfunction LVEF ≤ 40%). Arterial hypertension, diabetes mellitus and smoking are respectively present in 29, 7%, 21, 8% and 27, 7% of the patients. A history of rheumatic fever was present in 60, 8% of rheumatic valvular disease. The rheumatic etiology was the most important (50,5%). A preoperative coronary angiography was performed in 63,4% of the patients and coronary artery disease was associated to the valvular heart disease in 14,9%. Mitral valve replacement, aortic-valve replacement and double valve replacement were respectively performed in 38,7%, 35,4% and 18,7% of the cases. Bioprothesis were implanted in 5,29% of the cases. One eighth of the patients underwent coronary artery bypass graft in addition to the valvular surgery. In 16,8% of the cases it was a redo surgery. Contemporary epidemiological data show a rise of the degenerative etiology and associated coronary artery disease. Surgery offers good results for patients with significant valvular heart disease. Valve replacement and repair are the main surgical options. Older patients and redo procedures are increasingly frequent.

İnvestigation of endothelial dysfunction in children with acute rheumatic fever.

Background:Acute rheumatic fever (ARF) is an important cause of valvular heart disease in children. Endothelial dysfunction plays an important role in the pathogenesis of valvular heart diseases. The role of endothelial dysfunction in valvular heart diseases due to ARF is not exactly known. In ARF, autoimmune injury, inflammation, oxidative stress, and impairment of nitric oxide in valvular endothelium may be the causes of endothelial dysfunction. The purpose of this study is to evaluate endothelial dysfunction and arterial stiffness in children with ARF.Materials and Methods:Thirty-six patients diagnosed with ARF (the mean age was 11.80 ± 2.82 years) and 36 volunteered individuals with similar age, sex, and body mass index were included in the study. The study groups were compared in terms of M-mode echocardiography parameters, carotid arterial strain (CAS), beta-stiffness index (βSI), and flow-mediated dilation (FMD).Results:In patients with ARF, there was a decrease in FMD% (10.36 ± 7.26 and 12.76 ± 4.59; P < 0.001) compared to the control group. In addition, CAS (0.16 ± 0.06 and 0.18 ± 0.08; P = 0.44) and βSI (3.65 ± 1.61 and 3.57 ± 2.38; P = 0.24) were similar in the patient and the control groups. Furthermore, no correlation was detected between decreased FMD value and mitral regurgitation (r = −0.07; P = 0.66), aortic regurgitation (r = −0.04; P = 0.78), CAS (r = −0.08; P = 0.61), and βSİ (r = −0.20; P = 0.22).Conclusion:In our study, a decrease in FMD value, which is a marker of endothelial dysfunction, was found in children with rheumatic carditis.

Assessment of Knowledge, Attitudes and Practices (KAP) on Rheumatic Heart Disease among Senior Medical Students in Cameroon

Background: Rheumatic heart disease (RHD) is the commonest cause of valvular heart disease in low and middle-income countries (LMICs). The low cardiologist to patient ratio leaves a big challenge of RHD prevention and management to general practitioners in Cameroon. This makes it important to assess the aptitude of senior medical students who are doctors-to-be on RHD. This could thus give a base on which to increase awareness and decrease the burden of the disease. Therefore, we sort to evaluate the knowledge, attitudes, and practices (KAP) of senior medical students on rheumatic heart disease. General objective: To determine the level of knowledge, attitudes on rheumatic heart disease, and assess practices towards RHD and its prevention. Methodology: A cross-sectional study was conducted in four medical schools in Cameroon for a period of 3 months (from January 1st to April 1st, 2019). The senior medical students were recruited using a structured self-administered questionnaire and electronic forms. Data were entered into an excel spreadsheet and analysed with IBM SPSS version 25.0 for windows. The knowledge level was divided into tertiles (poor, moderate and good) while the attitudes and practices were divided into poor or good. Association to KAP was evaluated and Statistical significance was set at P < 0.05. Results: In total, 509 senior medical students (6th and 7th year) were recruited. The mean age was 24.6 (SD ± 1.7) with 53.2% of students in the 19 to 24 years-old range. There were more females (51.7%) and level 6 students (50.1%). Most of the students had moderate knowledge (58.2%), with good attitudes and practices on rheumatic heart disease and its prevention. One-quarter of the students had good knowledge, attitudes, and practices on rheumatic heart disease. Lecture on RHD, history of sore throat and study in faculty of health science (FHS) was associated with good knowledge, attitudes, and practices on RHD. Conclusion: Despite having most of the senior medical students (6th and 7th years) in Cameroon with moderate to good knowledge of RHD, only a third has an above-average knowledge. There is a modest knowledge of RHD that could be used as an important foundation upon which to build RHD educational programs to expand awareness and understanding. Every 1 in 4 senior medical students have good knowledge, attitude and practice on RHD.

Surgical options in rheumatic heart disease: an Indian surgeon's perspective.

Rheumatic heart disease is the primary cause of valvular heart disease in India and other Southeast Asian countries. The disease is quite different from that seen in France, USA, and Australia. Poverty, malnutrition, and delayed referral affect the outcomes. Rheumatic heart disease can affect all four heart valves, mitral being the most common, aortic second, tricuspid next, and finally the pulmonary valve. The combinations of mitral and aortic, mitral and tricuspid, and all three valves are the next in frequency. Acute rheumatic fever usually manifests as quadrivalvular involvement. However, chronic rheumatic quadrivalvular heart disease has also been reported. The technical aspects taught and practiced in one institution over the past four decades are described here. Closed mitral valvotomy, mitral valve repair, or replacement with mechanical, bioprosthetic, and autograft valves are the choices. Aortic valve disease is usually treated with valve repair or replacement with mechanical, homograft or pulmonary autograft valves.

Randomized Crossover Trial of Phosphate-binding Medication on Serum Phosphate Levels in Patients With Aortic Stenosis

PurposeAortic stenosis is a common cause of valvular heart disease with no means of prevention. The recognized association between aortic stenosis and serum phosphate raises the possibility of preventing progression of the disorder by using phosphate-binding drugs, but there is uncertainty whether such treatment lowers serum phosphate levels in patients without diagnosed renal failure. This pilot study was conducted to answer this question in patients with aortic stenosis. MethodsA randomized, double-blind, crossover trial of the phosphate-binding drug sevelamer was conducted in 72 patients. Patients were prescribed sevelamer 0.8 g (low-dose), sevelamer 2.4 g (high-dose), and matching placebo, 3 times daily with food; each regimen lasted 6 weeks and was allocated at random. Serum phosphate levels were measured at the end of each treatment period, and within-person levels were compared. FindingsSixty-one patients completed the 3 treatment periods. There was no significant difference in the mean end-treatment phosphate levels across all patients (3.38, 3.36, and 3.31 mg/dL with placebo, low-dose sevelamer, and high-dose sevelamer, respectively). Post hoc analysis showed a reduction in phosphate levels with increasing sevelamer dose in the highest baseline phosphate quartile group; a 0.3 mg/dL reduction (mean, 4.09 mg/dL with placebo, 3.95 mg/dL with low-dose sevelamer, and 3.79 mg/dL with high-dose sevelamer; Ptrend = 0.027). ImplicationsSevelamer had no overall statistically significant effect in lowering serum phosphate levels, but a reduction was observed in patients with phosphate levels in the highest quartile group of the population distribution. This hypothesis-generating result requires confirmation in an independent study. If confirmed, a trial of sevelamer in preventing the progression of aortic stenosis may be justified in patients with high phosphate levels. ISRCTN Registry identifier: ISRCTN17365679.

Prevalence, clinical characteristics and outcomes of valvular atrial fibrillation in a cohort of African patients with acute heart failure: insights from the THESUS-HF registry.

SummaryIntroductionRheumatic heart disease (RHD) is the commonest cause of valvular heart disease and a common cause of heart failure in sub-Saharan Africa (SSA). Atrial fibrillation (AF) complicates RHD, precipitates and worsens heart failure and cause unfavourable outcomes. We set out to describe the prevalence, clinical characteristics and outcomes of valvular atrial fibrillation in a cohort of African patients with acute heart failure (AHF).MethodsThe sub-Saharan Africa Survey of Heart Failure (THESUS-HF) was a prospective, observational survey of AHF in nine countries. We collected demographic data, medical history and signs and symptoms of HF. Electrocardiograms (ECGs) were done in a standard fashion. AF was defined as either a history of AF or AF on the admission ECG. Using Cox regression models, we examined the associations of AF with all-cause death over 180 days and a composite endpoint of all-cause death or readmission over 60 days.ResultsThere were 1 006 patients in the registry. The mean age was 52.3 years and 50.8% were women. AF was present in 209 (20.8%) cases. Those with AF were older (57.1 vs 51.1 years), more likely to be female (57.4 vs 49.1%), had significantly lower systolic (125 vs 132 mmHg) and diastolic (81 vs 85 mmHg) blood pressure (BP), and higher heart rates (109 vs 102 bpm). Ninety-two (44%) AF patients had valvular heart disease. The presence of AF was not associated with the primary endpoints, but having valvular AF predicted death within 180 days.ConclusionAF was present in one-fifth of African patients with AHF. Almost half of the AF patients had valvular disease (RHD) and were significantly younger and at risk of dying within six months. It is important to identify these high-risk patients and prioritise their management, especially in SSA where resources are limited.

Pathophysiological coronary and microcirculatory flow alterations in aortic stenosis.

Regulation of coronary blood flow is maintained through a delicate balance of ventriculoarterial and neurohumoral mechanisms. The aortic valve is integral to the functions of these systems, and disease states that compromise aortic valve integrity have the potential to seriously disrupt coronary blood flow. Aortic stenosis (AS) is the most common cause of valvular heart disease requiring medical intervention, and the prevalence and associated socio-economic burden of AS are set to increase with population ageing. Valvular stenosis precipitates a cascade of structural, microcirculatory, and neurohumoral changes, which all lead to impairment of coronary flow reserve and myocardial ischaemia even in the absence of notable coronary stenosis. Coronary physiology can potentially be normalized through interventions that relieve severe AS, but normality is often not immediately achievable and probably requires continued adaptation. Finally, the physiological assessment of coronary artery disease in patients with AS represents an ongoing challenge, as the invasive physiological measures used in current cardiology practice are yet to be validated in this population. This Review discusses the key concepts of coronary pathophysiology in patients with AS through presentation of contemporary basic science and data from animal and human studies.

Impacto de la etiología de la regurgitación mitral en la mortalidad tardía de pacientes tratados con MitraClip®

IntroductionMitral regurgitation is the second most common cause of valvular heart disease, and even though it involves so bad prognosis, almost a half of patients are rejected from surgical treatment. For this cohort of patients, it has treated with MitraClip® with promising outcomes in both functional and degenerative etiology of mitral regurgitation. Material and methodsRetrosprective observational study about features and outcomes of 72 patients underwent MitraClip® implantation from November 2011 to October 2016. ResultsMitral regurgitation etiology was functional (61.1%), degenerative (26.4%) or mixed (12.5%). The functional etiology was associated with lower age (67.9±8.74 vs 74.6±13.06 years old, P=.21) and lower left ventricular ejection fraction (34±8.5% vs 57±15%; P<.001). The median EuroSCORE-II was 3.84 (Q1-Q3 quartile: 2.21-8.10). There was no differences about the number of clips used (1.55±0.68 functional and 1.64±0.55 degenerative, P=.53) or the number of days in hospitalary admission after intervention (3.36 functional vs 3.7 degenerative; p=.56). Regurgitation reduction was partial (more than grade 2) in 4.5% of functional etiology and 14.3% of degenerative etiology (P=.145). No cases of in-hospital mortality or during the first month after discharge were reported. During an average follow up of 24 months it was reported 9 deaths (20.45%) in functional etiology and 2 deaths (7.14%) in degenerative/mixed etiology (P=.13). ConclusionMitraClip® treatment is safe and effective in patients with both functional and degenerative etiology of mitral regugitation, even though the last one seems to be associated with a lower late mortality rate.

Association between serum calcium, serum phosphate and aortic stenosis with implications for prevention.

Background Aortic stenosis is the most common cause of valvular heart disease with no means of prevention. Lowering serum levels of calcium or phosphate are potential preventive strategies but observational studies on the associations with aortic stenosis are inconsistent. Design and methods A case-control study was conducted in 132 individuals undergoing echocardiography (63 with aortic stenosis and 69 without) and the results combined with three other comparable studies (914 individuals overall) to provide a summary odds ratio of aortic stenosis for a 0.1 mmol/L increase (approximately one standard deviation) in calcium and phosphate respectively. The relationship between calcium and phosphate and the severity of aortic stenosis, according to peak trans-aortic velocity, was also examined in the case-control study using linear regression. Results Both calcium and phosphate were positively associated with aortic stenosis. The summary odds ratio for a 0.1 mmol/L increase in calcium was 1.79 (95% confidence interval 1.07-2.99), p = 0.027 and for phosphate it was 1.47 (1.08-2.01), p = 0.015. Peak trans-aortic velocity increased with phosphate levels, 9% (4%-14%) per 0.1 mmol/L, p = 0.001, but not with calcium, p = 0.089. Conclusions If the associations are causal and reversible, these results indicate that a small reduction in calcium or phosphate levels, within the physiological rage, would translate into a clinically significant reduction in the risk of aortic stenosis. Randomised trials of calcium and phosphate lowering therapies in aortic stenosis are needed.