Press conference: Rheumatic Heart Disease a forgotten but devastating disease

www.worldcardiocongress.org Chairpersons: Bongani M. Mayosi Jonathan Carapetis Press conference: Rheumatic Heart Disease a forgotten but devastating disease www.worldcardiocongress.org

www.worldcardiocongress.org RHD The Real World Situation L.Zühlke, G.Karthikeyan, M.Engel, B.Cupido, A.Joachim, R.Daniels S.Rangarajan, S.Yusuf, K.Teo, B.Mayosi. for the Rheumatic Heart Disease Global Registry (REMEDY) Investigators www.worldcardiocongress.org

Burden of Disease:Heart Failure Mayosi, B et al Heart 2007 7% 3% 12% 35% CHD Renal 17% Rheumatic Heart Disease 26% CMO EMF Ellis J et al Trop Doct 2007 Tamponade

Gunther et al The Lancet 2006 Diao M et al Arch Cardiovasc Dis. 2011

RhEuMatic Heart Disease RegistrY - REMEDY Rationale and Design Prospective, international (Africa and India), hospital-based registry; follow-up and outcome ascertainment at two-year follow-up N = 3000 The full study will aim to enroll 10,000 patients. Main objectives Karthikeyan G et al. Rationale and design of a Global Rheumatic Heart Disease Registry: The REMEDY study. American Heart Journal. 2012. To describe demographic and disease characteristics of contemporary patients To describe prevailing treatment patterns (Focus on adherence to and quality of oral anticoagulation, and adherence to secondary penicillin prophylaxis) Major outcomes (all-cause mortality, stroke/systemic embolism, major bleeding, RF)

Preliminary Results: Previous History n=690 15% 13% 10% 6% 6% 6% 5% 1% 2% 0% Infective Endocarditis Major Bleeding Peripheral Embolism Stroke Valvulopasty Previous surgery

Preliminary Results- n=690 Mild Moderate Severe 120 100 23 % NYHA 3 or 4 60 % diagnosed with Congestive Heart Failure 80 60 40 20 0 AR AS MR MS TS

Oral Anticoagulants Prescribed Preliminary Results- n=690 Awareness of Goal INR 55.3% 44.7% Yes No 65% 35% Yes No Measurements of INR in past 6 months 40% 30% 29% 33% 24% 20% 14% 10% 0% 1-2 3-5 6 or more none

RhEuMatic Heart Disease RegistrY - REMEDY Preliminary data Young patients (mean age) 30 years Proportion with AF 31.6% High-risk population 4.4% (15/341) all-cause mortality at 10-month follow-up Mean age of death: 50 years

In conclusion There is an irrefutable burden of disease relating to RHD in Africa and middle and low-income countries. REMEDY presents an opportunity for collaboration, in describing and documenting the course of a neglected disease. Initial results indicate significant disease burden and serious morbidity. There are important gaps in the prescription of and adherence to guideline-recommended treatments. This presents opportunities for focused intervention. REMEDY will be a source of valuable information for governments in formulating policy and guidelines for the control and treatment of RHD.

Thank you

www.worldcardiocongress.org Dr. Antonio Grimaldi, M.D. Cardiovascular and Thoracic Department, San Raffaele Scientific Hospital, Milan, Italy Rheumatic Heart Disease Remains a Major Cause of Heart Failure in Developing Nations The Ugandan Experience www.worldcardiocongress.org

BACKGROUND The increasing global crisis in Non-Communicable Diseases (heart disease, stroke, cancer, diabetes, etc.), is a barrier to UN development goals including poverty reduction, health equity, economic stability, and human security (Lancet 2011). In Africa, cardiovascular diseases are the second leading cause of mortality and the first under the age of 50 years. Uganda, like many other african countries, has an accelerated epidemiological transition with a marked increase in cardiovascular non-communicable diseases (Mayosi, Science 2009).

BACKGROUND Heart failure (HF) is a progressive disorder in which damage to the heart causes weakening of the cardiovascular system. HF is defined as the inability of the heart to supply sufficient blood to meet the needs of the body. HF is a major cause of mortality in the community. Identifying HF aetiology is crucial when planning interventions aimed to reduce mortality and morbidity.

ST. RAPHAEL OF ST. FRANCIS HOSPITAL NSAMBYA

AIMS During 2009-2010, 5 non-governmental organizations missions carried out by Italian medical teams (30 weeks) had the opportunity to prospectively collect clinical and echocardiographic data from patients referred to a urban Hospital in Kampala, Uganda. The objective of the study was to provide a hospital-based epidemiological picture of HF.

RESULTS Among 217 subjects referred for suspicion of heart disease, 150 were affected by heart disease. Most patients (97; 65%) presented with HF (median age 32 years, IQR 12-65, female 52%). The main cause of HF was RHD (n=29, 30%), mainly related to mitral valve regurgitation (60%). RHD is a complication of rheumatic fever and represents the predominant form of valvular disease affecting children and young adults. Among HF patients affected by RHD, 23 (79%) had an indication for cardiac surgery.

CONCLUSIONS RHD still remains the most common cause of HF in Uganda, with late presentation in most cases and heart failure in adulthood. The results should promote efficient cost-effective preventive measures focused on RHD: Screening programmes aimed to increase the community awareness concerning the RHD also promoting a wider diffusion of portable technologies. Education concerning major cardiovascular risk factors and chronic alcohol intake Beyond the preventive strategy there is an actual need for surgical interventions for heart failure related to RHD since cardiac surgery is not available in Uganda.

www.worldcardiocongress.org Andrea Z. Beaton, M.D. Children s National Medical Center, Washington DC Echocardiography-Based Screening for the Early Diagnosis of Rheumatic Heart Disease www.worldcardiocongress.org

Echocardiography for the Early Diagnosis of RHD Traditionally RHD was only diagnosed through clinical exam Disease was usually advanced

Echocardiography for the Early Diagnosis of RHD Finds more cases Is more accurate Can detect very early disease

Echocardiography for the Early Diagnosis of RHD Rheumatic Heart Disease found on echocardiogram before clinical symptoms exist is called subclinical RHD

Echocardiography for the Early Diagnosis of RHD

Echocardiography for the Early Diagnosis of RHD Since 2004 the World Health Organization has recommended echocardiography for RHD screening in high-prevalence regions

Echocardiography for the Early Diagnosis of RHD 5006 Available Children enrolled in 6 Screening Sites 4869 Children Screened (97%) 130 Children with Abnormal Screening Echo (2.4%) 72 Total RHD Cases (1.5%)

Echocardiography for the Early Diagnosis of RHD 5006 Available Children enrolled in 6 Screening Sites Prevalence rate of 1.5% 4869 Children Screened (97%) 130 Children with Abnormal Screening Echo (2.4%) 72 Total RHD Cases (1.5%)

Echocardiography for the Early Diagnosis of RHD 5006 Available Children enrolled in 6 Screening Sites 47 Sub-clinical RHD 4869 Children Screened (97%) 130 Children with Abnormal Screening Echo (2.4%) 72 Total RHD Cases (1.5%)

Echocardiography for the Early Diagnosis of RHD Children attending schools with lower socioeconomic representation were more likely Have RHD Have advanced disease Mean age of RHD positive (10.1 yrs) children higher than RHD negative children (9.3 yrs) May have implications for screening protocols

Echocardiography for the Early Diagnosis of RHD We are just beginning to learn about patients with subclinical RHD What is the natural history of subclinical RHD? 12-month Follow-Up Data Do they benefit from secondary prophylaxis?

Echocardiography for the Early Diagnosis of RHD 43 (60%) children presented for follow-up at 6 months 41 (57%) children presented for follow-up at 12 months 60 50 40 30 20 10 88% 8 17 53% 7 9 47 62% 29 58/88 (66%) 75% 16 12 0 Definite Probable Possible No Disease Total Patients Follow-up

Echocardiography for the Early Diagnosis of RHD 12 Month Disease Progression 0 5 10 15 20 25 30 35 Definite 5 2 13/58 (22%) showed improvement Probable 1 6 2 7/58 (12%) showed worsening Possible 22 5 2 None 9 3 Unchanged Improved Worsened

Echocardiography for the Early Diagnosis of RHD 12 Month Disease Progression 0 5 10 15 20 25 30 35 Definite 5 2 Probable 1 6 2 Resolution of MR Possible 22 5 2 None 9 3 Unchanged Improved Worsened

Echocardiography for the Early Diagnosis of RHD 12 Month Disease Progression 0 5 10 15 20 25 30 35 Definite 5 2 New regurgitant murmur Probable 1 6 2 Possible 22 5 2 None 9 3 Unchanged Improved Worsened

Echocardiography for the Early Diagnosis of RHD At 6 months 13/17 (76%) children prescribed penicillin showed >90% compliance At 12 months 8/15 (53%) had >90% compliance 9/9 boarding students receiving PCN from school nurse had 100% compliance at both visits

Echocardiography for the Early Diagnosis of RHD Follow-up of children diagnosed with RHD in a school-based echo-screening program is feasible Early follow-up shows dynamic disease development: both improvement and worsening More research is needed into improving rates of compliance with secondary prophylaxis The effectiveness and need of secondary prophylaxis in children with subclinical disease remains unclear

Echocardiography for the Early Diagnosis of RHD New evidence-based guidelines will allow for collaborations to determine the significance of sub-clinical disease

Echocardiography for the Early Diagnosis of RHD

www.worldcardiocongress.org Dr. Abdulkader A. Sharafadden, MMed Head of Cardiac Department at Algomhori Teaching Hospital, Taiz, Yemen Interventional Therapy and the Need for Earlier Intervention www.worldcardiocongress.org

Rheumatic Mitral Valve Stenosis An acquired progressive form of valvular heart disease caused by rheumatic fever Characterized by diffuse thickening of mitral valve leaflets, fusion of the commissures, shortening and fusion of the chordae tendineae Resulting in an obstruction of the blood flow from the left atrium to the left ventricle Leaflets Chordae papillary Mitral valve Normal Mitral stenosis

Therapy Medical - Prevention of recurrent rheumatic fever, - Prevention and treatment of complications - Monitoring disease progression to allow intervention at the optimal time point. PBMV Interventional - Percutaneous Balloon Mitral Valvuloplasty ( PBMV ) - Surgical intervention

1 st of June 2008 to 28 th of February 2009 87 patients

Inclusion criteria All patients were admitted and confirmed to have pure rheumatic mitral valve stenosis by echocardiography. Cases with compound and other rheumatic valves lesions were just included for statistical purposes.

Distribution of patients with RHD admitted to Cardiology Department at Algomhori Hospital Rheumatic valve lesion Mitral stenosis Pure mitral stenosis Mitral regurgitation Aortic stenosis Aortic regurgitation From Rheumatic Heart Disease (n= 206) 119 89 68 35 14 % 57.8 43.2 33 17 6.8 From total cardiac patients (n=1082) % 11 8.2 4.4 2.5 1.1 Total RHD 206-19%

Distribution of sex and mean age within patients with pure Rheumatic Mitral Stenosis Males 28.7 % Females 71.3 % M : F Ratio 1 : 2.4 Mean age 36.02 ±14.13 years

Degree of stenosis in patients with pure Rheumatic Mitral Valve Stenosis Mild 11.5% Severe 51.7% Moderate 36.8%

Recurrent Rheumatic Fever in patients with pure Rheumatic Mitral Stenosis Negative 60.9% Positive 39.1%

Adherence to secondary prophylaxis for Rheumatic Fever Positive 28.7% Negative 71.3%

Complications according to the degree of stenosis Degree of stenosis Complications Mild ( n=10 ) Moderate ( n=32 ) Severe (n=45 ) % % % P Pulmonary Hypertension ( n=83 ) 9 10.8 29 34.9 45 54.2 0.1 Pulmonary Congestion ( n=45 ) 6 13.3 18 40 21 46.7 0.61 Atrial Fibrillation ( n=35 ) 3 8.6 11 31.4 21 60 0.43 Right Ventricular Failure ( n=17 ) 2 11.8 5 29.4 10 58.8 0.77 Stroke ( n=11 ) 0 0.0 0 0.0 11 100 0.003 Frank Pulmonary Edema ( n=9 ) 0 0.0 3 33.3 6 66.7 0.44 Left Atrial Thrombus ( n=3 ) 0 0.0 0 0.0 3 100 0.24 Infective Endocarditis ( n=2 ) 0 0.0 0 0.0 2 100 2.3 Peripheral Embolisation ( n=1 ) 0 0.0 0 0.0 1 100 0.62

Hospital stay duration according to complications Hospital Stay Complications <1 week ( n=40 ) 1-2 weeks ( n=39 ) > 2 weeks ( n=8 ) % % % P Pulmonary Hypertension ( n=83 ) 38 45.8 37 44.6 8 9.6 0.8 Pulmonary Congestion ( n=45 ) 19 42.2 23 51.1 3 6.7 0.41 Atrial Fibrillation ( n=35 ) 7 20 25 71.4 3 8.6 0.00 Right Ventricular Failure ( n=17 ) 8 47 7 41.2 2 11.8 0.89 Stroke ( n=11 ) 3 27.3 1 9.1 7 63.6 0.00 0.00 Frank Pulmonary Edema ( n=9 ) 6 66.7 3 33.3 0 0.0 0.34 Left Atrial Thrombus ( n=3 ) 1 33.3 2 66.7 0 0.0 0.69 Infective Endocarditis ( n=2 ) 0 0.0 0 0.0 2 100 0.00 Peripheral Embolisation ( n=1 ) 1 100 0 0.0 0 0.0 0.53

Case fatality according to the degree of Mitral Valve Stenosis Degree of mitral stenosis Alive % Outcome Died % Mild (n= 10) 10 12.7 0 0.0 Moderate (n= 32) 32 40.5 0 0.0 Severe (n= 45) 37 46.8 8 100 Total 79 90.8 8 9.2

Percentages Case fatality according to complications 80 75 70 60 50 40 37.5 37.5 30 20 25 10 0 0 0 0

Percentages Plan of therapy in patients with Mitral Valve Stenosis 60% 50% 52.9 40% 30% 20% 28.7 18.4 10% 0% BMVP Surgical intervention Follow up

Performance of interventional therapy Surgical BMVP intervention Interventional Therapy Performed 4% Performed Performed 23.9% 34.8% Not performed Not Not performed 64.2% performed 76.1% 96%

Conclusions Mitral stenosis was the most common RHD within our community accounted for 57.8% while pure mitral stenosis accounted for 43.2% Females were more affected than males (M:F ratio 1:2.4) The detection rate of the Attack of rheumatic fever was low with only 39.1% and adherence to secondary chemoprophylaxis was weak among patients with only 28.7%..

Conclusions Most patients were in a late stage of the disease necessitating interventional therapy Case fatality was 9.2%, all noted among severe degree of stenosis Performance of interventional therapy was far lower than that required (23.9 %)

Recommendations Mitral stenosis requires 3 early: Early diagnosis Early prevention Early intervention

Recommendations Great efforts must be made to detect the first signs of Rheumatic fever and Rheumatic heart disease as this maybe the only clinically manifested visit at an early stage before it becomes subclinical and so be missed until the progression of disease or complications occur. Any auscultated murmur must be thoroughly investigated by echocardiography because secondary prevention and outcome of the disease relies on accurate case detection.

Recommendations Establishing a RHD Surveillance System for a better documentation and registration all over the country to facilitate health care planning. Screening programs for Rheumatic heart disease must be performed among elementary school children by echocardiography.

Recommendations Great efforts should be done to implement primary and secondary prevention programs for rheumatic fever and RHD including establishing health educational programs through different media. Advanced cardiac centers must be established throughout the country to facilitate accessibility to appropriate management including interventional therapies with less effort and free of charge.

Recommendations Reconsideration of the health strategy applied in Yemen concerning general practioners practice where they should be sent immediately after graduation to central hospitals to gain the adequate experience before sending them for rural services (primary care centers).

Benzathine penicillin BMVP Mitral valve replacement 10 years cost 20 years cost 200 $ 2000 $ 5000 $ 400$??????

Special Thanks Assoc. Prof. Ali Ahmed Ali Assoc. Prof. Hilal Lashuel Dr. Enas Ali Dammag

Q&A Session