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Abstrak :
Latar belakang: Diabetes mellitus tipe 2 (DMT2) dan gagal jantung memiliki keterkaitan yang kuat dan luaran klinis yang satu mempengaruhi lainnya. Studi terakhir berhasil membuktikan manfaat empagliflozin, obat lini kedua pada DMT2, terhadap kardiovaskular. Mekanisme seluler yang diketahui berperan pada hewan adalah efek antifibrosis miokard, namunbelum ada studi pada manusia.Tujuan: Mengetahui efek pemberian empagliflozin terhadap fibrosis miokard pada pasien DMT2 dengan gagal jantung. Metode: Uji klinis acak tidak tersamar yang dilakukan di RS Jantung dan Pembuluh Darah Harapan Kita dari Februari 2019 sampai Mei 2019. Pasien DMT2 dan gagal jantung diberikan empagliflozin 10 mg selama tiga bulan. Perbedaan kadar suppression of tumorigenicity-2 (ST2) serum pada kelompok kontrol dan intervensi di awal dan akhir penelitian akan dianalisis. Hasil: Terdapat 58 pasien yang menjadi subjek penelitian dan 40 (69%) pasien menyelesaikan penelitian. Terdapat perbedaan kadar ST2 yang bermakna setelah pemberian empagliflozin selama tiga bulan (median ST2 kelompok empagliflozin sebelum dan sesudah empagliflozin masing-masing 23,5(12,5 - 130,7)ng/mL dan 18,9(12,5 - 29,4) ng/mL, p=0,02). Penurunan ST2 dan persentase penurunan ST2 kelompok empagliflozin kedua kelompok tidak berbeda secara statistik (masing-masing p=0,16 dan p=0,21). Kesimpulan: Pemberian empagliflozin selama tiga bulan dapat menurunkan fibrosis miokard yang tidak terlihat pada kelompok kontrol. Tidak terdapat perbedaan besaran penurunan fibrosis pada pemberian empagliflozin dibandingkan terapi standar. ......Background: Type 2 diabetes mellitus (T2DM) and heart failure have a strong relationship; one affects each other. Recent studies have proven some cardiovascular benefits of empagliflozin. Myocardial antifibrosis is proposed to be the mechanism in many animal studies, but in humans the data is lack. Objectives: To investigate the effect of empagliflozin on myocardial fibrosis in T2DM patients and heart failure. Methods: This was an open-labeled clinical trial in National Cardiovascular Center Harapan Kita, from February 2019 to May 2019. Patients with T2DM and heart failure received empagliflozin 10 mg for three months. Differences of serum suppression of tumorigenicity-2 (ST2) levels in both control and intervention groups at the beginning and end of the study were analyzed. Results: There were 58 patients enrolled in the study and total of 40 (69%) patients completed it. There were significant differences in ST2 levels after administration of empagliflozin (median for ST2 empagliflozin group before and after empagliflozin was 23.5 (12.5 - 130.7) ng / mL and 18.9 (12, 5 - 29.4) ng / mL respectively, p = 0.02). The ST2 value difference and percent different were not different (p=0,16 and p=0,21, respectively). Conclusion: Three months Empagliflozin might reduce myocard fibrosis which was not seen in control group. The total fibrosis reduction was not significantly different compared to standard therapy

Abstrak :
Latar belakang: Stenosis mitral SM akibat penyakit jantung reumatik PJR memiliki disfungsi sistolik ventrikel kiri VK secara subklinis bila menggunakan parameter global longitudinal strain GLS walaupun rata-rata pasien memiliki fraksi ejeksi FE baik. Pada PJR, inflamasi kronis menyebabkan terjadinya nekrosis fibrinoid, pada akhirnya menjadi fibrosis miokard. Berdasarkan teori ini, fibrosis miokard merupakan salah satu dasar teori yang mendasari disfungsi sistolik VK pada SM. Namun hingga kini penelitian yang menilai hubungan ini belum ditemukan.Tujuan: Mengetahui hubungan GLS sebagai parameter fungsi sistolik dengan volume fibrosis VK pada SM akibat PJR.Metode: Studi potong lintang melibatkan pasien SM akibat PJR akan menjalani pemeriksaan MRI jantung untuk mengevaluasi fibrosis miokard dengan metode LGE dan ekokardiografi untuk menilai GLS. Kedua data diolah menggunakan analisa korelasi.Hasil: Terdapat 36 pasien subjek penelitian. Volume fibrosis miokard rata-rata VK 4,9 2,7 . Walaupun FE baik median 62 , nilai GLS menurun dibandingkan nilai rujukan normal 13,5 3,9 . GLS memiliki korelasi sedang dengan volume fibrosis VK r = -0,432; p 0,009 . Tidak ada korelasi antara GLS dengan area katup mitral maupun gradien tekanan transmitral rata-rata. Tidak didapatkan juga korelasi antara FE dengan volume fibrosis.Kesimpulan: GLS memiliki korelasi sedang dengan volume fibrosis VK pada pasien SM akibat PJR.

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Abstract Background. The correlation between the extent of myocardial fibrosis and subclinical LV systolic dysfunction in rheumatic mitral stenosis MS has not been widely studied. We sought to evaluate the correlation between the extent of LV myocardial fibrosis quantified by Late Gadolinium Enhancement LGE CMR and Global Longitudinal Strain GLS by Speckle Tracking Echocardiography STE in these patients.Methods. We prospectively evaluated 36 consecutive rheumatic MS patients who were planing to undergo intervention in our center. Then we evaluate the correlation between the extent of LV myocardial fibrosis quantified by Late Gadolinium Enhancement LGE CMR and Global Longitudinal Strain GLS by Speckle Tracking Echocardiography STE Results. Thirty six patients showed mean of LGE was 4,9 2,7 . Despite good ejection fraction median 59.5 , IQR 28 68 , the LV GLS was reduced mean 13.5 3.9 compared to normal reference value. There was moderate correlation between GLS and LGE r 0,432 p 0,009 . There are no correlations between GLS with mitral valve area MVA and mean mitral valve gradient mean MVG . No significant correlation was found between ejection fraction and LGE.Conclusion. There was moderate correlation between LGE and GLS in patients with rheumatic MS. Keywords Myocardial fibrosis global longitudinal strain late gadolinium enhancement CMR rheumatic mitral stenosis

Abstrak :
Latar belakang: Prevalensi penyakit ginjal kronis (PGK) adalah sebesar 13,4% dari seluruh populasi global. Sindrom kardiorenal (SK) tipe 4 menyebabkan 40% mortalitas pada pasien PGK. Salah satu mediator dalam patogenesis SK adalah stres oksidatif yang dapat mengakibatkan disfungsi endotel, fibrosis miokardial dan penebalan dinding ventrikel. Terapi obat golongan penghambat reseptor angiotensin (ARB) dan statin mempunyai efek antiinfalamasi dan antioksidan terhadap jantung. Hal ini menjadi pertimbangan penggunaannya untuk memperbaiki kondisi stres oksidatif pada SK. Hingga saat ini belum banyak diketahui pengaruh pemberian ARB dan statin pada jantung dengan SK. Tujuan: Penelitian ini bertujuan untuk mengetahui pengaruh pemberian kombinasi ARB + statin terhadap fibrosis miokardial dan tebal dinding ventrikel jantung pada tikus PGK dengan metode 5/6 nefrektomi. Metode: Penelitian ini menggunakan organ jantung tersimpan dari tikus jantan Sprague-Dawley yang terdiri atas 5 kelompok perlakuan dan masing-masing terdiri atas 4 sampel: kelompok kontrol (sham), 5/6 nefrektomi (Nx), 5/6 nefrektomi dengan terapi irbersatan 20mg/kgBB/hari selama 4 minggu (Nx + Ir), 5/6 nefrektomi dengan terapi simvastatin 10mg/kgBB/hari selama 4 minggu (Nx + S), dan 5/6 nefrektomi dengan terapi irbersatan 20mg/kgBB/hari dan simvastatin 10mg/kgBB/hari selama 4 minggu (Nx + Ir-S). Sampel organ jantung tersimpan dipotong secara cross-sectional dan diamati gambaran histopatologinya (HE dan Masson’s trichrome) menggunakan aplikasi ImageJ. Data kemudian dianalisis secara statistik menggunakan One-Way Anova. Hasil: Pemberian terapi baik irbersatan, simvastatin, maupun kombinasi keduanya selama 4 minggu menunjukkan persentase luas area fibrosis miokardial dan tebal dinding ventrikel jantung yang cenderung lebih kecil dibanding kontrol namun tidak bermakna secara statistik. Terapi irbesartan, kombinasi irbesartan dan simvastatin, dan simvastatin menunjukkan persentase luas area fibrosis dan tebal dinding ventrikel jantung yang paling kecil secara berurutan. Kesimpulan: Pemberian kombinasi ARB dan statin selama 4 minggu belum dapat memperbaiki fibrosis miokardial dan hipertropi dinding ventrikel jantung pada tikus model PGK. Diperlukan penelitian lebih lanjut dengan menggunakan dosis yang lebih besar, dengan perlakuan lebih lama serta jumlah sampel yang lebih banyak agar efek kombinasi lebih nyata terlihat ......Background: The prevalence of chronic kidney disease (CKD) is 13.4% of the entire global population. Cardiorenal syndrome (SK) type 4 causes 40% mortality in CKD patients. One of the mediators in the pathogenesis of SK is oxidative stress which can lead to endothelial dysfunction, myocardial fibrosis and ventricular wall thickening. Angiotensin receptor blocker (ARB) and statin inhibitor class drugs have anti-inflammatory and antioxidant effects on the heart. This is a consideration for its use to improve oxidative stress conditions in SK. Until now, it has not been widely known the effect of ARB and statin administration on the heart with SC. Objective: This study aims to determine the effect of ARB + statin combination on myocardial fibrosis and ventricular wall thickness in CKD rats using the 5/6 nephrectomy method. Methods: This study used stored heart organs from male Sprague-Dawley rats consisting of 5 treatment groups and each consisting of 4 samples: control group (sham), 5/6 nephrectomy (Nx), 5/6 nephrectomy with radiation therapy. 20mg / kgBW / day for 4 weeks (Nx + Ir), 5/6 nephrectomy with simvastatin therapy 10mg / kgBW / day for 4 weeks (Nx + S), and 5/6 nephrectomy with 20mg / kgBW / day irresistible therapy and simvastatin 10mg / kgBB / day for 4 weeks (Nx + Ir-S). Stored cardiac samples were cut cross-sectional and observed histopathologically (HE and Masson's trichrome) using ImageJ application. Data were then analyzed statistically using One-Way Anova. Results: The treatment of both irbers, simvastatin, and a combination of both for 4 weeks showed that the percentage of myocardial fibrosis area and the thickness of the heart ventricles tended to be smaller than the control but not statistically significant. Irbesartan therapy, a combination of irbesartan and simvastatin, and simvastatin showed the smallest percentage of fibrosis area and ventricular wall thickness, respectively. Conclusion: The combination of ARB and statin for 4 weeks has not been able to improve myocardial fibrosis and ventricular wall hypertrophy in CKD mice. Further research is needed using a larger dose, with a longer treatment and a larger number of samples so that the combined effect is more visible

Abstrak :
ABSTRAK
Latar belakang: disglikemia adalah keadaan intoleransi glukosa berupa peningkatan kadar gula darah yang berhubungan dengan risiko penyakit kardiovaskular. Seiring dengan waktu, pada akhirnya diabetes akan menimbulkan kerusakan pada target organ, salah satu yang penting adalah pada sistem organ kardiovaskular, dapat berupa penyakit jantung koroner, kardiomiopati diabetes, penyakit serebrovaskuler, dan penyakit arteri perifer. Diabetes juga meningkatkan risiko terjadinya gagal jantung. Pada kardiomiopati diabetes, proses fibrosis yang masih reversibel sudah mulai terjadi bahkan ketika penderita masih asimtomatik. Pemeriksaan baku emas untuk mendeteksi terjadinya fibrosis miokard secara dini adalah pemeriksaan histopatologi jaringan miokardium melalui biopsi. Akan tetapi pemeriksaan ini sangat invasif dan tidak nyaman bagi subjek. Pemeriksaan yang kemudian berkembang adalah pencitraan menggunakan Cardiac Magnetic Resonance Imaging (CMRI). Akan tetapi pemeriksaan ini cukup mahal, dan tidak tersedia pada semua fasilitas kesehatan. Sementara itu, ST2 adalah penanda enzim jantung yang menggambarkan derajat proses fibrosis yang sedang terjadi pada miokard, terutama pada keadaan gagal jantung. Pemeriksaan menggunakan penanda enzim dapat menjadi alternatif dengan keuntungan lebih murah, dapat terjangkau luas dan mudah tersedia. Tujuan: Mengetahui hubungan antara kadar ST2 serum dengan fibrosis miokard interstisial pada penderita disglikemia. Metode: Pasien disglikemia yang lolos kriteria eksklusi berupa komorbid kardiovaskular akan menjalani pemeriksaan kadar ST2 serum dan T1 relaxation time menggunakan Cardiac MRI. Selanjutnya dilakukan analisis hubungan antara kadar ST2 serum dan T1 relaxation time. Hasil penelitian: Sebanyak 34 pasien diikutsertakan ke dalam penelitian ini. Didapatkan kisaran nilai kadar ST2 serum antara 12.40-53.22 ng/dL (median 19.95 ng/dL). Rerata nilai T1 relaxation time didapatkan sebesar 443.39 ± 113.35 ms. Terdapat korelasi bermakna antara kadar ST2 serum dengan fibrosis diffuse miokardium (Spearman correlation r = -0,547, p < 0.01). Pada analisa multivariat hubungan antara kadar ST2 serum dan T1 relaxation time tidak dipengaruhi oleh faktor perancu yang telah ditetapkan (r = -0,44, p = 0,033). Kesimpulan: Hasil penelitian ini menunjukkan kadar ST2 serum berkolerasi dengan fibrosis diffuse miokardium pada populasi disglikemia.ABSTRACT
Background: disglycemia is a state of glucose intolerance include increased blood sugar levels associated with risk of cardiovascular disease. Over time, eventually diabetes will cause damage to the target organ, especially the cardiovascular system, which include coronary heart disease, diabetic cardiomyopathy, diabetes, cerebrovascular disease, and peripheral arterial disease. Diabetes also increases the risk of heart failure. The clinical appearance of the disease is wide ranging from asymptomatic to symptomatic heart failure. Gold standard examination to detect the occurrence of early myocardial fibrosis is histopathological examination of myocardial tissue via biopsy. However, these tests are very invasive and uncomfortable for the subject. Examination which later evolved is imaging using cardiac magnetic resonance imaging (CMRI). However, these tests are quite expensive, and not available at all health facilities. Meanwhile, ST2 is a cardiac enzyme marker that describes the degree of fibrosis process in the myocardium, especially in the state of heart failure. Examination using enzyme markers can be a cheaper alternative, widely accessible and readily available. Aim: Knowing the relationship between serum levels of ST2 with myocardial interstitial fibrosis in disglycemic patients. Methods: Disglycemic patients who passed from the exclusion criteria (cardiovascular comorbid), will undergo a serum ST2 levels and T1 relaxation time using cardiac MRI. Then we analyzed the relationship between serum levels of ST2 and T1 relaxation time. Results: A total of 34 patients were included in this study. The range values of serum ST2 levels were between 12.40-53.22 ng/dL (median 19.95 ng/dL). The mean value of T1 relaxation time were 443.39 ± 113.35 ms. There is a significant correlation between serum levels of ST2 with diffuse myocardial fibrosis (Spearman correlation r = -0.547, p <0:01). Multivariate analysis showed the relationship between serum levels of ST2 and T1 relaxation time is not influenced by confounding factors (r = -0.44, p = 0.033). Conclusion: ST2 serum levels correlates with diffuse myocardial fibrosis on disglycemic population.;Background: disglycemia is a state of glucose intolerance include increased blood sugar levels associated with risk of cardiovascular disease. Over time, eventually diabetes will cause damage to the target organ, especially the cardiovascular system, which include coronary heart disease, diabetic cardiomyopathy, diabetes, cerebrovascular disease, and peripheral arterial disease. Diabetes also increases the risk of heart failure. The clinical appearance of the disease is wide ranging from asymptomatic to symptomatic heart failure. Gold standard examination to detect the occurrence of early myocardial fibrosis is histopathological examination of myocardial tissue via biopsy. However, these tests are very invasive and uncomfortable for the subject. Examination which later evolved is imaging using cardiac magnetic resonance imaging (CMRI). However, these tests are quite expensive, and not available at all health facilities. Meanwhile, ST2 is a cardiac enzyme marker that describes the degree of fibrosis process in the myocardium, especially in the state of heart failure. Examination using enzyme markers can be a cheaper alternative, widely accessible and readily available. Aim: Knowing the relationship between serum levels of ST2 with myocardial interstitial fibrosis in disglycemic patients. Methods: Disglycemic patients who passed from the exclusion criteria (cardiovascular comorbid), will undergo a serum ST2 levels and T1 relaxation time using cardiac MRI. Then we analyzed the relationship between serum levels of ST2 and T1 relaxation time. Results: A total of 34 patients were included in this study. The range values of serum ST2 levels were between 12.40-53.22 ng/dL (median 19.95 ng/dL). The mean value of T1 relaxation time were 443.39 ± 113.35 ms. There is a significant correlation between serum levels of ST2 with diffuse myocardial fibrosis (Spearman correlation r = -0.547, p <0:01). Multivariate analysis showed the relationship between serum levels of ST2 and T1 relaxation time is not influenced by confounding factors (r = -0.44, p = 0.033). Conclusion: ST2 serum levels correlates with diffuse myocardial fibrosis on disglycemic population.;Background: disglycemia is a state of glucose intolerance include increased blood sugar levels associated with risk of cardiovascular disease. Over time, eventually diabetes will cause damage to the target organ, especially the cardiovascular system, which include coronary heart disease, diabetic cardiomyopathy, diabetes, cerebrovascular disease, and peripheral arterial disease. Diabetes also increases the risk of heart failure. The clinical appearance of the disease is wide ranging from asymptomatic to symptomatic heart failure. Gold standard examination to detect the occurrence of early myocardial fibrosis is histopathological examination of myocardial tissue via biopsy. However, these tests are very invasive and uncomfortable for the subject. Examination which later evolved is imaging using cardiac magnetic resonance imaging (CMRI). However, these tests are quite expensive, and not available at all health facilities. Meanwhile, ST2 is a cardiac enzyme marker that describes the degree of fibrosis process in the myocardium, especially in the state of heart failure. Examination using enzyme markers can be a cheaper alternative, widely accessible and readily available. Aim: Knowing the relationship between serum levels of ST2 with myocardial interstitial fibrosis in disglycemic patients. Methods: Disglycemic patients who passed from the exclusion criteria (cardiovascular comorbid), will undergo a serum ST2 levels and T1 relaxation time using cardiac MRI. Then we analyzed the relationship between serum levels of ST2 and T1 relaxation time. Results: A total of 34 patients were included in this study. The range values of serum ST2 levels were between 12.40-53.22 ng/dL (median 19.95 ng/dL). The mean value of T1 relaxation time were 443.39 ± 113.35 ms. There is a significant correlation between serum levels of ST2 with diffuse myocardial fibrosis (Spearman correlation r = -0.547, p <0:01). Multivariate analysis showed the relationship between serum levels of ST2 and T1 relaxation time is not influenced by confounding factors (r = -0.44, p = 0.033). Conclusion: ST2 serum levels correlates with diffuse myocardial fibrosis on disglycemic population.;Background: disglycemia is a state of glucose intolerance include increased blood sugar levels associated with risk of cardiovascular disease. Over time, eventually diabetes will cause damage to the target organ, especially the cardiovascular system, which include coronary heart disease, diabetic cardiomyopathy, diabetes, cerebrovascular disease, and peripheral arterial disease. Diabetes also increases the risk of heart failure. The clinical appearance of the disease is wide ranging from asymptomatic to symptomatic heart failure. Gold standard examination to detect the occurrence of early myocardial fibrosis is histopathological examination of myocardial tissue via biopsy. However, these tests are very invasive and uncomfortable for the subject. Examination which later evolved is imaging using cardiac magnetic resonance imaging (CMRI). However, these tests are quite expensive, and not available at all health facilities. Meanwhile, ST2 is a cardiac enzyme marker that describes the degree of fibrosis process in the myocardium, especially in the state of heart failure. Examination using enzyme markers can be a cheaper alternative, widely accessible and readily available. Aim: Knowing the relationship between serum levels of ST2 with myocardial interstitial fibrosis in disglycemic patients. Methods: Disglycemic patients who passed from the exclusion criteria (cardiovascular comorbid), will undergo a serum ST2 levels and T1 relaxation time using cardiac MRI. Then we analyzed the relationship between serum levels of ST2 and T1 relaxation time. Results: A total of 34 patients were included in this study. The range values of serum ST2 levels were between 12.40-53.22 ng/dL (median 19.95 ng/dL). The mean value of T1 relaxation time were 443.39 ± 113.35 ms. There is a significant correlation between serum levels of ST2 with diffuse myocardial fibrosis (Spearman correlation r = -0.547, p <0:01). Multivariate analysis showed the relationship between serum levels of ST2 and T1 relaxation time is not influenced by confounding factors (r = -0.44, p = 0.033). Conclusion: ST2 serum levels correlates with diffuse myocardial fibrosis on disglycemic population.