PROPOSAL
PENELITIAN PENGEMBANGAN ILMU KEDOKTERAN Left Atrial Strain as A Novel Imaging Biomarker in Prediction of Atrial Fibrillation in Patients with Cryptogenic
Stroke
Tim Pengusul
Ketua Peneliti : Prof. Dr. Hamed Oemar, PhD, SpJP(K), FJCC (8882430017)
Anggota Peneliti : Dr. Kemal Imran, SpS (8886999920)
FAKULTAS KEDOKTERAN PROGRAM STUDI KARDIOVASKULER
UNIVERSITAS MUHAMMADIYAH PROF. DR. HAMKA TAHUN 2021HALAMAN SAMPUL
HALAMAN PENGESAHAN Penelitian Ilmu Kedokteran Judul Penelitian
Left Atrial Strain as A Novel Imaging Biomarker in Prediction of Atrial Fibrillation in Patients with Cryptogenic Stroke
Patomekanisme Steatosis Akibat Defisiensi Vitamin B12; Kajian Stres Oksidatif Jenis Penelitian :Penelitian Ilmu Kedokteran
Ketua Peneliti : Prof. Dr. Hamed Oemar, PhD, SpJP(K), FIHA, FJCC.
Link Profil simakip :http://simakip.uhamka.ac.id/pengguna/show/1199
Contoh link: http://simakip.uhamka.ac.id/pengguna/show/978 Fakultas : Fakultas Kedokteran
Anggota Peneliti : Dr. Kemal Imran, SpS, MARS Link Profil simakip :Click or tap here to enter text.
Contoh link: http://simakip.uhamka.ac.id/pengguna/show/978 Anggota Peneliti :dr Adhimas Euro
Link Profil simakip :Click or tap here to enter text.
Contoh link: http://simakip.uhamka.ac.id/pengguna/show/978 Waktu Penelitian : 6 Bulan
Luaran Penelitian
Luaran Wajib :Jurnal Nasional Terakreditasi sinta 3 Status Luaran Wajib : In Review
Luaran Tambahan : conference Status Luaran Tambahan : presented
SURAT KONTRAK PENELITIAN
ABSTRAK
Background
One of the most common causes of atrial fibrillation (AF) is left atrial (LA) dysfunction, which is characterized by failed of LA mechanical function, which in turn produce AF as commonest cause of ischemic cryptogenic stroke (CS). To date, the assessment of LA dysfunction has still just confined to field of research or observational study and remains difficult to show up in routine clinical practice.
Objectives
The objective of this study was to explore whether LA strain can be used as echocardiographic biomarkers in daily clinical practice to predict the occurrence of PAF in patients with CS. By establishing a powerful of diagnostic tool we expect it would be easier for daily practice to utilize this model in order to simply predict an emersion of silent paroxysmal AF (PAF).
Methods
Sixty-two patients with CS who were divided into normal sinus rhythm, NSR group (n=48) and persistent AF (n=14) underwent LA mechanical function analysis using echocardiographic velocity vector imaging (VVI). LA volume (LAV), LA volume index (LAVI), emptying fraction (LAEF), LA reservoir strain (LARS) and global longitudinal strain (GLS) were measured during sinus rhythm.
Results
We found there was statistically gradual decreased of LAEF, LARS and GLS obtained from normal subjects, those from none documented paroxysmal AF (No AF), proven AF and persistent AF, respectively. ROC curve analyses for the ability of LAEF, LARS and GLS to predict occurrence of silent PAF (n = 29) from those who have not (n= 19) have been demonstrated. The AUC analysis showed a significance of its curve for LAEF and GLS, p = 0.008 and p = 0.012, respectively. The cut-off points of the LAEF of <50%, GLS of <20% and LARS of <23.2% have equal sensitivity and specificity 70% and 65% as their average value, respectively. LAEF, GLS and LARS were identified as the echocardiographic predictors with the highest AUC.
Conclusion
In conclusion, documented LA strain as a novel biomarker is associated with the high possible occurrence of PAF and therefore it could be applied in daily clinical practice to ensure that PAF must be appear with long-term ECG monitoring even though it is still in sinus rhythm.
Key words: Atrial strain, atrial fibrillation, biomarker, echocardiography, cryptogenic stroke.
BAB 1. PENDAHULUAN
Cryptogenic stroke (CS) is defined as a stroke of undetermined aetiology due to two or more causes being identified, negative evaluation, or incomplete evaluation. It is often hypothesized to have originated from distant source of embolization that mostly from the cardiac chamber. Recent studies established that structural, functional and electrical remodelling of the LA are correlated to the emersion of AF (1).
Stroke is the leading cause of death and long-term disability worldwide. Up to 30
% of all ischemic strokes are attributed to cardio-embolism (2), and approximately 25–40 % are cryptogenic stroke (CS), where a distinct etiology has not been elucidated (3). CS is intended to be a stroke with a lack of clearly definable etiology despite thorough investigation, known as embolic stroke of undetermined sources, ESUS (4, 5). CS is often assumed to have begun from distant embolization (6). A number of studies have found a correlation between CS and the emergence of atrial fibrillation (AF) - thus giving rise to the hypothesis that CS events mostly originated from the occurrence of silent AF. Therefore, because of the difficulty of capturing atrial arrhythmias, especially non-valvular AF in the CS subgroup with long-term ECG monitoring, and the potential benefits of anticoagulant therapy, precise noninvasively guiding are required to detect even minor LA function abnormalities.
In term of methodological technique, 2D speckle tracking technology to analyse strain and strain rate of LA mechanical function, a study by Motoki et al (7) concluded that both speckle tacking echocardiography (STE) and velocity vector imaging (VVI) are statistically comparable to use in clinical practice. LA strain imaging, which is a non-invasive examination, has been shown to detect sub- clinic abnormalities in LA mechanics (including LA reservoir and booster pump function), therefore, it is very useful in this subgroup of CS cases (8).
BAB 2. TINJAUAN PUSTAKA
Identifying AF has been a leading research main concern in the past decade, this is because of fast introduction of oral anticoagulation has significancy declined subsequent stroke risk (9). As an outcome, paroxysmal AF detection is essential, as determining this diagnosis will ready the clinician to change the standard post- stroke treatment of antiplatelet agents to anticoagulants therapy. On the other hand, however, in the clinical practice they found difficulty to capture occult AF using the regular ECG recordings or even long-term Holter monitoring, because the appearance of AF is often hidden, silent, or not trapped during patient’s clinic visit. Long-term ECG monitoring is the reference method to assess silent PAF for prompt anti-coagulation prevention (10). However, routine use of long-term ECG monitoring is not possible for economic reason and selecting patients who are likely to have paroxysmal AF (PAF) is defying as there is currently no established model to predict an occurrence of PAF.
AF has a progressive nature, leading to structural, functional, and electrical changes in the left atrium (LA) of the heart (11). LA remodeling consists of mechanical, electrical, and structural changes. These changes are present prior of the emergence of AF and worsen with development of AF (12,13,14). An abnormality in LA function can induce thrombus formation in the LA wall through the process of blood stasis even though it is independent of incident AF (12). This suggests that AF and structural changes accompanied by impaired LA function have an interplay each other, but the end result is unfavorable, CS events occurs (8). The problem is the lack of informed knowledge for clinicians to explore more the LA function which is accordingly simple and very useful.
Examination of LA function as an important part of routine examination using strain echocardiography.
The aim of this study is to seek for a powerful and highly accurate model of noninvasive diagnostic as well as easy-to-use independent predictor of LA function to assess functional and structural abnormalities of LA functions that are believed to be the cause of blood stasis that would leading to CS. The urgency of this study is to inhibit of recurrent stroke which is mandatory because it has been shown to increase mortality and disability in the CS stroke population. By performing LA function with echocardiographic mechanical strain would be giving a greatly help clinicians determining the appropriate therapy in CS patients with or without AF.
BAB 3. METODE PENELITIAN Study Population
This study was retrospective cohort from the institutional clinical and echocardiographic data base of ischemic stroke patients at the National Brain Center Hospital. Eligible patients were diagnosed with ischemic stroke based on clinical findings by attending neurologists together with imaging proven on Computed Tomography Scan and/or Brain Magnetic Resonance Imaging. Sixty- two patients who suffered from ischemic stroke both those admitted and after discharge from the Brain Center Hospital (Rumah Sakit Pusat Otak Nasional) Jakarta, Indonesia, between January 2021 and October 2021 were included in the present study. Among them, 14 ischemic stroke patients those have been diagnosed as persistent AF (Persi-AF) were also included in this study for the purpose of comparison of their LA mechanical functions.
Eligible patients were those with ischemic stroke that had been diagnosis as Cryptogenic Stroke (CS) after excluding any causes thru blood laboratory examination, carotid ultrasound examination and brain imaging, and those suspected having cardioembolic in origin. We also included 22 normal healthy subjects in sinus rhythm those having no history of any stroke in order to compare their normal level of LA mechanical function. Stroke was considered cryptogenic by attended neurologist in absence of (i) major-risk cardioembolic sources, (ii) more than 50% luminal stenosis in the extracranial or intracranial arteries supplying the infarcted area, and (iii) an unrevealing diagnostic stroke workup otherwise, resulting in a trial of ORG 10172 in acute stroke treatment (TOAST) classification of 5 or stroke of undetermined aetiology (15).
Subjects with cardiac valve disease, primary myocardial infarction, congestive heart failure, prosthetic valves, cardiomyopathy, infective endocarditis, cardiac tumor, patent foramen ovale, and pericardial diseases were excluded from the study. All patients have been performed a thorough examination to exclude any causal of stroke and further confirmed as Cryptogenic Stroke (Embolic Stroke of Undetermined Source, ESUS). Comorbid conditions such as diabetes, hypertension, heart failure, and history of stroke were taken into account to risk- stratify the subjects according to CHADS2 criteria.
Echocardiographic Study
All eligible patients underwent transthoracic echocardiographic study after initial treatment in the emergency department, or in the neurology ward (in-patients) or within one week after discharge from the hospital (out-patients), and who had received a cardiac mobile long-term 72-h ECG Holter monitoring. Two- Dimensional Echocardiographic with Apical 4-Chamber sectional view has been performed to each patient and record in video imaging then it stored in CD-ROM package data with the number of heartbeat minimal 3 beats as ECG guided along
echocardiographic examination. We perform echocardiographic examination by following the standard procedure of Echo Examination Guideline published by AHA (American Heart Association, 2016) and ASE (American Echocardiography Association, 2018).
Author will focus on examination and analysis the special chamber of the heart, i.e. the LA mechanical function or its remodeling, by using soft-ware VVI, Velocity Vector Imaging (Echo Machine - Siemens SC2000; and the soft-ware Siemens Syngo Ultrasound Apps Suite, Release Version 1.7A, Germany), at its Siemens Work Station. The whole patients at the first visit to the Neuro- cardiology Clinic will be divided into 3 subgroups, i.e., patients without paroxysmal AF (subgroup No AF), patients with proven paroxysmal AF after long-term 72 hours Holter Monitoring (subgroup-PAF), and patients with Persistent AF since 1st visit (subgroup Persistent AF).
In CS group, we performed resting ECG for initial selection and separated those with normal sinus rhythm (NSR) from those with Persistent AF. Furthermore, transthoracic echocardiography for evaluating LA function that was focused to measure LA mechanical function parameters including LA volume, LA emptying fraction, LA reservoir strain and global longitudinal strain. In those with NSR group and Persistent AF group the 72-hour long-term ECG Holter monitoring were not performed. Table-I shows NSR subject group and three sub-groups of CS patients.
Table-I. Study Design and Data Collection
Patient with ischemic stroke and normal subject shall have to be performed a resting ECG, then 2-D Echocardiography as their baseline data. Sub-group will be separated after 3-day Holter monitoring.
Figure-1. Sample of LA Strain VVI (velocity vector imaging) in normal subject and in patient with AF. Left and right panels demonstrating apical long-axis view (four-chamber views) with the LA as region of interest. Left panel shows longitudinal strain at the LA reservoir period from a healthy individual with normal atrial deformation, while right panel demonstrates a reduced atrial deformation during atrial systole in a patient with AF during the study. AF, atrial fibrillation
Statistical Analysis
All data are expressed as mean + SEM. The subgroups were compared by one- way analysis of variance (ANOVA) for multiple comparisons. Differences were considered statistically significant at p<0.05. Continuous variables are expressed as mean + SD. Student’s t test
was used to compare the LAVI, LAEF, LARS and GLS variables between No PAF subgroup and PAF subgroup. A box plot was used to identify outliers of LAVI, LAEF, LARS and GLS measurements. Points that were beyond the quartiles by 1.5 interquartile range were deemed to be outliers. The analysis was performed using IBM SPSS version 25.0 software (IBM Co., Armonk, NY, USA).
BAB 4. HASIL DAN PEMBAHASAN
Clinical patient characteristics:
Baseline patient characteristics and clinical risk factor are summarized in Table II.
Among the CS patients No-PAF and PAF subgroups are no different in term of age and gender. There are 32 males (40.6% without PAF and 59.4% with proven PAF). The age above 60 years old, there are 43.8% male in No-PAF subgroup and 56.3% in proven PAF subgroup. There was no significant difference between the two sub-groups in the characteristics of age, gender, and several risk factors such as hypertension, diabetes mellitus, smoking, dyslipidemia, and obesity.
Table-II. Patient Characteristics According to Clinical Risk Factors.
This table shows patient characteristics according to cardiovascular risk factors.
There is no significantly different between two sub-group, regarding various clinical risk factors in those without proven PAF and proven PAF after prolonged ECG 72-h monitoring, p>0.05.
Figure-2. Left Atrial mechanical function constructed by velocity vector imaging (VVI) in a healthy individual (sinus rhythm), patient without proven PAF (No PAF) and patient with proven PAF (PAF), respectively, who underwent a 72-hour Holter ECG monitoring.
LA function of normal subject and CS patients represented by the left atrial emptying fraction (LA-EF) and reservoir strain (LA-RS) were gradually decreased in patients without proven PAF (paroxysmal Atrial Fibrillation) and became lowest with proven PAF, respectively; as well as conversely being gradually increased in its volume during systole was demonstrated in Fig.2.
Figure 3. Distribution Of Left Atrial Reservoir Strain (LARS) and LA Global Longitudinal Strain (GLS).
Abbreviations: No PAF= No detected PAF but sinus rhythm; PAF = Paroxysmal Atrial Fibrillation; Persi-AF = Persistent Atrial Fibrillation during the whole study.
The distribution of LA mechanical functional components (LA Reservoir Strain at the left-site and Global Longitudinal Strain at the right-side) are shown in the figure-3. After being analysed from normal subject and from each subgroup of patients with CS, the decreased of above values are statistically significant among each subgroup, (p<0.05). There were significant differences in the distribution of LASR as well as in the GLS in the CS patients without proven AF (No-AF) subgroup and in those with proven AF (PAF) subgroup). The lowest value of both strain parameters are noted in those CS patients with persistent AF (Persi-AF), (p<0.05).
Figure 4. Left Atrial Emptying Fraction (LAEF) and Left Atrial Volume Index (LAVI).
Left atrial emptying fraction at left-site and LA volume index at right-side, which were derived from normal subjects and from each sub-groups of patients with CS are demonstrated in the figure-4. The decreased of above values are statistically significant (p<0.05).
The results of statistical analysis showed a significant sharp gradual decrease starting in sequent from the healthy subject (Normal) group, No-PAF, PAF and the lowest in the Persi-AF subgroup.
Table-III. Univariate Predictor of AF Occurrence in Patients with Cryptogenic Stroke
Comparison of two subgroups, No PAF, patients without proven PAF; and PAF those who have proven PAF after long-term 72-h ECG monitoring toward the variables of LA mechanical function.
The above table shows significant difference between two subgroups, CS patients without early proven PAF (No-PAF subgroup) and those with proven PAF subgroup on their LA mechanical function: LA Emptying Fraction (p = 0.003), LA Global Longitudinal Strain (p = 0.008), and LA Reservoir Strain (p = 0.05).
Statistical data was calculated by using bivariate analysis.
Figure 5. Receiver Operating Characteristic – ROC Curve.
ROC curve analyses for the ability of LA-EF, LA Reservoir Strain and GLS to discriminate patients predicted to have PAF between the subgroup without PAF among the study population of CS patients. Representation of LA mechanical dysfunction including LA-EF, GLS and Reservoir Strain having significantly predictor for future AF in patient with CS. ROC curve analyses for the ability of LAEF, GLS and LARS to predict patients with Cryptogenic Stoke who have silent PAF (n = 29) from those who have not (n= 19). The ROC curve (Fig.5) shows a fairly good threshold, because it has an almost high true-positive rate and a low false-positive rate. The results of the AUC analysis demonstrated a
significance of the AUC curve for LA Emptying Fraction (LAEF) and LA Global Longitudinal Strain (GLS), p = 0.008 and p = 0.012, respectively.
Figure-6. The Summarized of the ROC Curve Analysis.
ROC curve analysis to the LA mechanical variables, LAEF, LA GLS and LARS.
The cut-off points of the LA mechanical function parameter values, i.e. LA emptying fraction (LAEF) of less than 50%, GLS of less than 20% and LA reservoir strain (LARS) of less than 23.2% have equal sensitivity and specificity 70% and 65% as average value, respectively. LAEF, and GLS were identified as the echocardiographic predictors with the highest AUC.
DISCUSSION
AF and LA myopathy are considered important contributors to thromboembolism in at least 30% of cryptogenic stroke (16). Development and subsequent embolization of atrial thrombi can occur with any form (i.e., paroxysmal, persistent, or permanent) of AF, while detection of PAF is very vital and most difficult, even using available monitoring telemetric ECG. On the other hand, AF detection is pivotal since it will change the standard post stroke treatment from antiplatelet agents to anticoagulant or event atrial catheter ablation in order to avoid recurrence cardioembolic stroke (17).
The aim of this study was to further develop and apply a simple echocardiographic measurement to detect LA mechanical dysfunction in order to predict the risk of recurrence of PAF or occult AF in patients after acute CS.
Echocardiography has been the imaging technique of choice for evaluating the LA because of its widespread availability and ease of use. We wished to examine the cut-off value of LA strain at any period during systolic and diastolic phases. In this study, we utilized a new method for prediction of PAF using strain echocardiography VVI. We want to introduce to cardiologists as well as cardiac technicians who work in the echo laboratory in order to use the present simple technique in order to predict occult AF in patient with ischemic CS.
Measurement of LA strain is a novel technique that quantifies segmental and global LA myocardial mechanics in both sinus rhythm and AF. LA strain evaluates the longitudinal shortening and lengthening of segments of the LA myocardium throughout the cardiac cycle. The resultant strain curves quantify the LA conduit function (peak positive LA strain), booster function (peak negative strain [in patients with coordinated atrial contraction]), and the reservoir function (total LA strain). Decreased LA strain (indicative of worse LA mechanical function) has been associated with the development of AF (14).
LA mechanical function, in term of LA emptying fraction (LAEF), LA reservoir strain (LA RS) and global longitudinal strain (GLS) could single out patients with PAF without apparent cardiac dysfunction assessed by traditional imaging methods from healthy individuals. Therefore, we focused on assess LA mechanical function to predict those with possible having atrial arrhythmia especially occult AF. Kim D. et al (18) have demonstrated the value of LA global longitudinal strain assessed by speckle tracking echocardiography well discriminates the presence of appendage thrombus on TEE in patients with acute ischemic stroke. In our study, prediction of the cause of thrombus formation in the LA and/or in the LA appendage is the main focus.
LA remodelling was described as an important prognostic marker in different diseases, including in condition of atrial arrhythmias. So, the physiology of LA function can explain the whole work of atrial contraction and relaxation. Even the assessment can be performed by 2-D echocardiography, its detailed quantification remains challenging (19,20). LA contractile function is dependent on preload, afterload, intrinsic contractility, atrial electrical activation, and electromechanical coupling. The propagation of electrical impulses occurs via interatrial connections in the LA subepicardial tissue (21). This event results in the activation of the LA, which moves from the interatrial septum to the inferior, anterior, and lateral walls of the LA during sinus rhythm. Any change in this pathway can prolong or abolish interatrial conduction, and thus create a substrate for the onset of atrial arrhythmias (22).
The principal mechanical role of the LA is to modulate left ventricular filling and cardiovascular performance; this is accomplished by its distinct, but inter-related functions as a reservoir for pulmonary venous return during ventricular systole, as a conduit for pulmonary venous return during early ventricular diastole, and as a booster pump that augments ventricular filling during late ventricular diastole (13). Enlargement of the LA chamber is thought to be a prompting component for atrial remodelling which then initiate the development of AF. However, the
physiologically precise association of LA remodelling related to LA enlargement in various diseases is not as simple as that of cardiovascular physiology (23).
Data from our study demonstrate that sequent decrease of LA mechanical functions from those CS subgroup, non-detected AF (No-PAF), PAF and then Persi-AF subgroup, consecutively (Figure-3 and 4). From the present data, we should come to convincing conclusion that a very low LA Strain value can be confirmed as having AF, even sometimes it has not been caught on the ECG recording. However, in this regard, we do agree with the clinical report from Patel et.al (24), that thrombus formation in the LA not only caused by AF but also initiated by atrial myopathy.
The principal findings in the present study are that (i) LA mechanical dysfunction assessed by VVI reflect the presence of high-risk findings for cardio-embolism in Persi-AF subgroup, where it can be the best diagnostic value for the presence of low stasis, and have confidence a presence of thrombus in the LA or in the LA Appendage. (ii) LA emptying fraction (LAEF) is a potential sensitive and powerful biomarker to predict an occurrence of paroxysmal AF in patients with acute CS. (iii) The LA mechanical function is independently linked of other cardiovascular risk factors, such as old age, gender and obese. Overall, the assessment of LA mechanical function using strain-based echocardiographic VVI is useful for risk assessment of cardio-embolism in patients with ischemic CS. In this regard, LA strain could be the best choice as a simple but powerful predictor to any emerge of occult AF.
BAB 5. KESIMPULAN DAN SARAN CONCLUSION
In conclusion, the value of LA emptying fraction, LA strain in reservoir phase and global longitudinal could be a novel biomarker non-invasive index for predicting an emerge of paroxysmal AF in acute CS. Therefore, it could be benefit for cardiologists as well as neurologists in their practical setting to warrant cardio- embolic sources. Any poor LA mechanical function detected by LA strain assessment, presumption that a source of the thrombo-embolism should be originated from LA chamber and/or LA appendage which is interpreted due to low wall compliance and increased stiffness, that further most likely a consequence of occurrence of paroxysmal AF or atrial myopathy without arrhythmia.
STUDY LIMITATION
Firstly, we set up only an ECG long-term monitoring just 72 hours, that we do worry day-after the patients cannot be monitored continuously throughout the follow-up period; consequently, asymptomatic episodes of AF might not have been detected, leading to an underestimation of the true rate of AF recurrence.
Secondly, the number of participants who enrolled in this present study is very small that is due the unwanted situation as Covid-19 pandemic in Indonesia reached its peak level of infectious people that happened from January to September 2021. Consequently, such tremendous situation had triggered a big panic and scary of numerous patients as well as doctors, eventually adding the number of participants to the present study was completely blocked and impossible.
BAB 6 LUARAN YANG DICAPAI
Luaran yang dicapai berisi Identitas luaran penelitian yang dicapai oleh peneliti sesuai dengan skema penelitian yang dipilih.
Jurnal
IDENTITAS JURNAL
1 Nama Jurnal 2 Website Jurnal 3 Status Makalah 4 Jenis Jurnal 4 Tanggal Submit
5 Bukti Screenshot submit Pemakalah di seminar
IDENTITAS SEMINAR
1 Nama Jurnal Isiscam
2 Website Jurnal https://isicam.id/
3 Status Makalah submitted 4 Jenis Prosiding
4 Tanggal Submit 27 Nov3mber
5 Bukti Screenshot submit
Pemakalah di seminar
IDENTITAS HAK KEKAYAAN INTELEKTUAL
1 Nama Karya 2 Jenis HKI 3 Status HKI
4 No Pendaftaran
BAB VII RENCANA TINDAK LANJUT DAN PROYEKSI HILIRISASI
Minimal mencakup 2 hal ini.
Hasil Penelitian the value of LA emptying fraction, LA strain in reservoir phase and global longitudinal could be a novel biomarker non-invasive index for predicting an emerge of paroxysmal AF in acute CS. Therefore, it could be benefit for cardiologists as well as neurologists in their practical setting to warrant cardio-embolic sources. Any poor LA mechanical function detected by LA strain assessment, presumption that a source of the thrombo-embolism should be originated from LA chamber and/or LA appendage which is interpreted due to low wall compliance and increased stiffness, that further most likely a consequence of occurrence of paroxysmal AF or atrial myopathy without arrhythmia.
Rencana Tindak
Lanjut Melakukan penelitian lanjutan, untuk menambah jumlah sampel
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LAMPIRAN (bukti luaran yang didapatkan)
1
LAPORAN KEMAJUAN PENELITIAN 100%
dan
KENDALA PENELITIAN 19-11-2021
1. JUDUL PENELITIAN:
Left Atrial Strain as A Novel Imaging Biomarker in Prediction of Atrial Fibrillation in Patients with Cryptogenic Stroke.
2. IDENTITAS PENGUSUL A. PENELITI UTAMA:
Prof. Dr. Hamed Oemar, PhD, SpJP(K), FIHA, FJCC. (NIDN: 8882-43-0017) B. ANGGOTA PENELITI:
Dr. Kemal Imran, SpS, MARS (NIDN : 8886-99-9920)
3. NOMOR KONTRAK : 90 / F.03.07 / 2021; Tanggal KONTRAK: 19 April 2021 4. PELAKSANAAN PENELITIAN:
A. PERSIAPAN PENELITIAN:
Persiapan untuk mengumpulkan data ekokardiografi beserta analisa biomarker dari sejumlah pasien-pasien Iskemik Stroke di RSPON - baik yang rawat jalan maupun rawat inap - berjalan dengan sangat baik dan lancar. Pengumpulan data secara cross-sectional retrospective. Namun, sejak April 2021 laju “Pengumpulan dan Analisa Data” mulai terganggu dan terhambat disebabkan oleh meningkatnya kasus infeksi COVID-19 di RSPON dan ketakutan psikologis serta ke-enggan-an pasien-pasien untuk berkunjung dan berobat; hal ini menyebabkan jumlah pengumpulan terhambat, penambahan data baru sangat berkurang secara drastis.
B. PENGUMPULAN DATA DAN ANALISA STATISTIK
Penelitian ini adalah penelitian kolaborasi antara spesialis penyakit jantung (cardiologists) dan spesialis syaraf (neurologists).
Subjek Penelitian adalah pasien-pasien yang telah mendapat kepastian diagnostik dari para Spesialis Syaraf di RSPON sebagai “Cryptogenic Ischemic Stroke”
(Stoke Iskemik Kriptogenik, artinya Stroke yang tidak diketaui sebab-sebabnya).
Jumlah data pasien-pasien (N) yang berhasil dikumpulkan masih belum cukup dari target yang akan dihitung dan dianalisa secara statistik. Namun, sebagai Kemajuan Penelitian 70% telah kami laporakan dan upload ke Website Simakip UHAMKA. Jumlah data (N) pada laporan 100% ini juga tidak bertambah karena praktek echocardiography dan kunjungan pasien baru dimulai buka kembali di RSPON.
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Namun, kami mencoba melakukan Analisa Statistik oleh Peneliti Utama beserta Anggota Peneliti.
[ANALISA STATISTIK: Lihat Laporan 100% jumlah sampel pasien terbatas].
Pada saat awal penelitian dan dilanjutkan pada saat ini kami telah melakukan Enrolment/Selection/Analisa Statistik dengan mematuhi Persyaratan Kriteria Inklusi dan Eksklusi [Lihat Preliminary Report]. Data subjek penelitian adalah pasien-pasien Stroke Iskemik Kriptogenik, yaitu mereka yang telah lengkap data dasar, data esensial terkait erat dengan kebutuhan penelitian, termasuk sbb:
1) Data Klinik (simptom, faktor risiko, pemeriksaan penunjang neurologi, diagnostik akhir, saran-saran, dll.)
2) Data EKG Resting (atau pada saat awal berkunjung di RSPON) 3) Data EKG jantung dengan Holter Monitoring 24-jam
4) Data rekaman EKG jantung dengan Holter Monitoring 72-jam (3-hari berturut-turut)
5) Data Ekokardiografi dan Doppler Ekokardiografi.
a. Breakdown subjek penelitian terhadap Kelompok STROKE ISKEMIK KRIPTOGENI, total jumlah sekarang 62 pasien subject (N=62) dibagi kedalam 3 sub-kelompok (sub-group), sesuai screening awal dengan sandapan-rekaman EKG Holter Monitoring- selama 72-jam, non-stop.
Hasil pemisahan dari sampel pasien stroke dibagi kedalam 3-subgrup, sebagai berikut:
I. Tidak muncul gangguan irama selama Monitoring EKG – 72-jam, diberi label sebagai Tanpa Atrial Fibrillation (AF), atau No AF subgroup. Jumlah 19 orang (N=19);
II. Ditemukan rekaman gangguan irama tidak teratur pada rekaman EKG, didiagnosa sbgi AF, mereka ini digolongkan sebagai Paroxysmal Atrial Fibrillation subgroup. Jumlah 29 orang (N=29)
III. Sejak awal pertemuan dengan (wawancara) telah ditemukan pada EKG resting adalah AF, - tanpa melalui Rekaman EKG jangka-panjang, mereka digolongkan sebagai Persistent Atrial Fibrillation subgroup (N=14). dan
Kelompok KONTROL yaitu data yang sama dari sejumlah orang sehat atau normal control (relawan normal dan sehat) terdiri dari 22 orang.
C. KONSOLIDASI DENGAN ANGGOTA PENELITI
Konsolidasi dengan anggota tetap maupun anggota pembantu di RSPON berjalan dengan sangat baik. Kami saling membantu untuk melakukan persiapan, dan analisa statistik dengan data yang tersedia.
D. IZIN KOMITE ETIK
Kami telah mengirimkan surat resmi ke Dirut RSPON tentang permohonan presentasi dihadapan Anggota Komite Etik RSPON. Sekarang dalam masa menunggu keluarnya izin resmi untuk penambahan data pasien-pasien di RSPON.
3 E. KENDALA PENELITIAN
Sejak April 2021, kita semua tidak menyangka terjadi kenaikan tajam kasus infeksi COVID19 pada masyarakat DKI, dan beberapa wilayah – propinsi di Indonesia. Pemerintah - beberapa bulan kemudian- mengeluarkan kebijakan PPKM, dan seterusnya angka kejadian menjadi turun dan naik dan turun lagi.
Keadaan serba tidak menentu.
Pada bulan Mei 2021, sejumlah tenaga medis di RSPON terpapar COVID19 sampai berjumlah sekitar 90 orang, bahkan lebih. Alhamdulillah, semuanya selamat dan sembuh kembali setelah dirawat di RSPON. Kejadian diatas ini menyebabkan Pimpinan RSPON mengeluarkan kebijakan dengan menghimbau agar terus dalam kewaspadaan dan kehati-hatian terhadap wabah tersebut kepada semua tenaga medis termasuk para dokter tetap dan dokter kontrak.
Khusus kepada para dokter-dokter yang telah berusia sama atau diatas 65 tahun diminta praktek on-line melalui Telemedicine dari rumah masing-masing.
Kebijakan RSPON. Sejak bulan Mei 2021, RSPON menutup Poliklinik Jantung terutama POLIKLINIK Ekokardiografi. Alasan penutupan adalah karena pemeriksaan ekokardiografi – yang menjadi ujung tombak penelitian ini - bahwa jarak fisik antara pasien dengan dokter terlalu dekat.
Oleh sebab itu, pimpinan RSPON mengambil kebijakan untuk keselamatan NAKES, dengan menghentikan sementara kegiatan Poliklinik Jantung dan Pemeriksaan Noninvasif Ekokardiografi sambil menunggu perkembangan lebih lanjut. Pada pertengahan Oktober 2021, Poliklinik Jantung dan Pemeriksaan Ekokardiografi dibuka kembali khusus untuk Ekokardiografi Transtorakal saja, atau disebut TTE (Transoesophageal echocardiography).
F. USULAN PENELITIAN
Kami mengusulkan kepada Pimpinan LEMLIT (Lembaga Penelitian dan Pengembangan) UHAMKA agar PENELITIAN KLINIK ini diberikan kesempatan tenggang waktu 6 bulan (ENAM BULAN) lagi untuk menyelesaikan kegiatan penelitian ini kembali, sampai tercapai jumlah subjek sampel penelitian sesuai perhitungan statistik, yaitu kurang-lebih 300 subjek.
Seterusnya PENELITI DAN ANGGOTA PENELITI siap mempublikasikan hasil penelitian ini kedalam jurnal international ber-akreditasi terindex SCOPUS.
G. KEMAJUAN PENELITIAN.
Disampaikan Bersama Laporan Kemajuan serta Kendala Penelitian. Laporan Kemajuan (100%) akan di-upload kedalam website SIMAKIP UHAMKA.
4 LAMPIRAN:
PERHITUNGAN STATISTIK BESAR SAMPLE PENELITIAN KLINIK UNTUK PENELITIAN YANG SEDANG BERLANGSUNG INI.
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Suasana Pekerjaan di Bagian Ekokardiografi – Department of Neuro-cardiology RSPON
Gambar-1. Pada foto ini, saya sedang melakukan pemeriksaan pasien penyakit jantung di RSPON pada masa awal Maret 2020. Kejadian Pandemik Covid19 belum merebak luas.
[Perhatikan kedekatan fisik antara dokter-pasien; keadaan terpaksa ini berisiko amat tinggi -high-risk -untuk transfer virus].
Gambar-2. Foto diatas ini diambil pada 14 Oktober 2021, dimana keadaan penyebaran infeksi Covid19 di wilayah DKI dan di RSPON sudah mulai reda, PPKM-1. Namun, semua NAKES tetap waspada sehingga Protokol Kesehatan saat pemeriksaan pasien-pasien tetap berjalan.
