Brugada-induced Severe Hyponatremia : Could it be lethal?

S.P. Mahaley ¹, Irnizarifka², C. Sukmagautama³, H. Arifianto²

¹General Practitioner

²Departement of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Sebelas Maret, Sebelas Maret University Hospital, Surakarta, Indonesia.

²Departement of Internal Medicine, Sebelas Maret University Hospital, Faculty of Medicine, Universitas Sebelas Maret, Indonesia.

 

Background: Brugada syndrome, first described in 1992, is a major cause of sudden cardiac death, syncope and ventricular tachyarrhythmia in people with no structural heart disease. Brugada syndrome usually manifests during adulthood, with a mean age of sudden death of 41±15 years old.

Case illustration: 58 years old male was admitted to RS UNS with fatigue for 3 days. Along with other physical and laboratory examinations, patient was diagnosed as having septic shock. As soon as transferred to high care unit, patient was having pulseless ventricular tachycardia but 3 minutes CPR was able to get him back with soporous condition. Laboratory showed severe hyponatremia (128 mEq/l) and baseline ECG evidenced type 1 Brugada. The 3% NaCl was administrated until his sodium level went up to 141 mEq/l. Patient’s condition was improved and brugada pattern ECG was back to normal. Patient was then discharged in good condition without any further cardiac events.

Discussion: Brugada syndrome is characterized electrocardiographically by ST segment elevation in the right precordial leads, followed by a negative T wave unrelated to ischemia, and prone to rapid polymorphic ventricular tachycardia capable of degenerating into ventricular fibrillation. The ECG pattern may be dynamic and is often concealed. Sodium channel blockers, drugs, electrolyte imbalances, fever and several other clinical circumstances are recognized inducers of a Brugada type 1 ECG in susceptible patients.

Conclusion: We have managed temporary but deadly type-1 Brugada Syndrome in septic patient through sodium level improvement. Brugada-induced severe hyponatremia did exist and might be lethal, thus accurate diagnosis must be done to generate definite treatment and convert ECG pattern to normal.

 

Keyword: brugada induced, severe hyponatremia, ventricular tachycardia

 

Role of Radiofrequency Ablation for Idiopathic Right Ventricular Outflow Tract Arrhythmias: a case report

S.P.I Nasruddin¹, Irnizarifka^1,2

¹Departement of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia.

²Departement of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Sebelas Maret, Sebelas Maret University Hospital, Surakarta, Indonesia.

 

Background: Premature Ventricular Contraction (PVC) is very common arrhythmia found in clinical practice. It may occur in healthy individual with no evidence of structural heart disease and most originate from right ventricular outflow tract (RVOT)¹. Idiopathic RVOT-PVC typically presents between the ages of 20 to 50 years and more frequent in women. When highly symptomatic or refractory to antiarrhythmic therapy, catheter ablation is recommended due to its > 95% success rate and a extremely low complication risk².

Case illustration: 27-year-old female came to outpatient clinic with chief complaint of recurrent palpitation. Frequent RVOT origin PVCs (unifocal, 50%) with coupling interval of 360 msec were obtained on Holter ECG monitor. Echocardiography did not evidence any structural heart diseases and revealed normal LVEF, whereas cardiac CT showed normal coronary arteries. Magnetic resonance imaging was done and revealed normal cardiac chamber, with no sign of arrhythmogenic right ventricular dysplasia or arrhytmogenic mitral valve prolapse. Verapamil was then initiated, but failed to improve her symptom and ECG. Electrophysiological study was finally done and showed unifocal RVOT-PVC with focal area at anteroseptal region. Radiofrequency ablation was performed (40 watts, 50⁰ celsius, 180 msec) without any complications. Evaluation showed normal sinus rhythm with no inducible PVC, and patient did not experience any more symptoms.

Conclusion: We have managed a young woman with frequent idiopathic RVOT-PVCs who are still symptomatic despite optimal anti-arrhythmic medication. Echocardiography, cardiac CT, and MRI showed no underlying structural heart disease and exclude arrhythmogenic right ventricular dysplasia. Timely decision to do radiofrequency ablation is particularly effective and safe to treat persistent and symptomatic idiopathic RVOT-PVC, with very low complication rate.

 

Keyword: radiofrequency catheter ablation, right ventricular outflow tract arrhythmia, premature ventricular contraction.

 

2:1 Atrioventricular Block : what can we learn from atropine effect?

Tridamayanti A ¹, Irnizarifka^1,2

¹Departement of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia.

²Departement of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Sebelas Maret, Sebelas Maret University Hospital, Surakarta, Indonesia.

 

Background: 2:1 atrioventricular block can occur in either AV node (AVN) or HIS-Purkinje System (HPS) and cannot be classified into type I or type II second-degree AV block because there is only one PR segment to be examined before the dropped-beat. On the other hand, it is essential to have two consecutive conducted P waves to differentiate between type I or type II second-degree AV block. Determining those types of atrioventricular or HPS block is very important as treatments are also unlike.

Case Illustration : 56 year old diabetic woman was admitted with chief complaint of chest pain since 15 hours beforehand, accompanied with diaphoresis and near syncope. Her resting ECG revealed 2:1 AV block, with PR interval was not prolonged (0.2 sec), and ST segments were not elevated. Cardiac enzyme proved diagnosis of NSTE-ACS and 2:1 AV block. In order to define the site of block, we performed atropine challenge test. After administration of 0.5 mg atropine, ECG revealed improvement of AV conduction ratio with 3:2 Wenckebach-like manners. It indicated the location of the block was at AV node.

Discussion: Fixed 2:1 AV block poses a diagnostic dilemma because it can be difficult to determine the site of block by the surface ECG alone. The AVN is richly innervated and highly responsive to both sympathetic and vagal stimuli, whereas HPS is influenced minimally by the autonomic nervous system. Atropine or exercise can improve AVN conduction because of sympathetic stimulation and/or parasympatholysis. Therefore, atropine administration can improve AVN conduction but worsen infranodal block due to sympathetic stimulation of the sinus node and AVN without changing the HPS refractoriness.

Conclusion: This case illustrates the importance of noninvasive atropine challenge test to confirm site of 2:1 atrioventricular block, thus will guide the definite therapy.

 

Keyword: 2:1 atrioventricular block, atropine challenge test, wenckebach, HIS-purkinje block

 

Left Ventricle Non Compaction: Could it be Reversed Back?

Left Ventricle Non Compaction: Could it be Reversed Back?

 

S.P. Mahaley¹, Irnizarifka², H. Arifianto²

¹General Practitioner, ² Cardiologist at UNS Hospital, Department of Cardiology and Vascular Medicine, Sebelas Maret University

  

Introduction

Left Ventricular non-compaction (LVNC), also known as ‘spongy myocardium is a rare abnormality of the left ventricular (LV). It is a pathophysiological process involving the arrest of the normal compaction of the embryonic sponge-like meshwork of interwoven myocardial fibers. Heart failure remains the most common presentation besides arrhythmias, and propensity for thromboembolism (21-24%). Impaired filling and abnormal relaxation leading to diastolic heart failure could also result from prominent trabeculations. With its under-developed myocardium, its reversibility is in question.

The diagnosis could be established primarily based on echocardiography with contrast ventriculography, CT and MRI as additional examination. LVNC on echocardiogram typically characterized by two-layered myocardial structure with thin compacted outer (epicardial) band, a much thicker non-compacted inner (endomyocardial) layer and deep myocardial trabeculae, particularly in the apex and free wall of the LV.

One reported that beta blocker may have benefits for LV function, and this may improves prognosis.  At that study, LVEF increased from 30% to 57% using beta blocker treatment, particularly carvedilol. Left ventricular end diastolic volume, end systolic volume, and end diastolic pressure decreased strikingly after treatment. After adequate therapy, non-compacted myocardium occupied a smaller percentage of the total ventricular wall area than before treatment.

Case

This is a case report of 56 years old woman who came to outpatient clinic of UNS hospital with chief complain of chest discomfort. She was recently diagnosed with HF due to ischemic cardiomyopathy, but has worsening symptoms despite optimal ischemic medications. Her metabolic profile and kidney function were within normal limit.

Echocardiography showed dilated all chamber, global hypokinetic, 15% LVEF with moderate mitral regurgitation. Echocardiography also proved a two-layered structure with a thin, compacted layer (C) and a thickened noncompacted layer (NC) at end-systole with ratio of NC/C >2, which ensures diagnosis of LVNC. Coronary CT angiography confirmed normal coronary arteries, which made us decide to stop standard ischemic therapies given to improve her compliance.

Furosemide, ramipril, and bisoprolol were initiated and uptitrated according to guidelines. Education regarding her disease and the importance of her compliance was routinely done every month. After 3 months, her functional class improved dramatically under 10 mg ramipril, 5 mg bisoprolol, and on demand 40 mg furosemide. Echocardiography evaluation evinced increase in LVEF (23.5%) and reduction of NC area.

Summary

LVNC is rare disease that has been increasingly diagnosed in clinical practice. There is no specific therapy for LVNC, thus adequate education should follows optimal guidelines directed medical therapy (GDMT) in order to produce better outcome. We have managed 56 years old woman with LVNC and prove its early reversibility through adequate education and simpler GDMT.

 

Keywords : LV Non Compaction, Echocardiography, Education, GDMT, Reversibility

 

 

 

Factors Influencing the Outcome of Hypertensive Hospitalized Patients, the Importance of Glycemic Control

Factors Influencing the Outcome of Hypertensive Hospitalized Patients, the Importance of Glycemic Control

 

External validation of Cardio-Renal Scoring System VKPP (Validated Kidney Protection Program) in Patients with Acute Decompensated Heart Failure

External validation of Cardio-Renal Scoring System VKPP (Validated Kidney Protection Program) in Patients with Acute Decompensated Heart Failure

Irnizarifka, Hersunarti N, Rahardjo SB, Putri VK, Soerarso R, Siswanto BB.

 

Background : Although the management of Heart Failure (HF) has developed, prognosis still not significantly improved. It is due to comorbidities, especially worsening renal function (WRF), which also plays a major role in the pathophysiology of HF. In 2015, Putri et al have developed a scoring system (VKPP score) to predict WRF in patients with Acute Decompensated Heart Failure (ADHF), in which predictors are female, Hb < 12.5 mg/dl, admission creatinine > 2.5 mg/dl, history of hypertension, and age > 75 years . This scoring system yields discrimination value of 0.682 (95% CI; 0.630 to 0.734). External validation of the VKPP scoring system needed in order to implement them clinically.

Objective : To validate externally the VKPP Cardio-Renal scoring system in patients who are hospitalized with ADHF.

Methods : This is a retrospective cohort study with temporal external validation method that performed at the Department of Cardiology and Vascular Medicine, Universitas Indonesia/NCCHK, using secondary data from September 2015 until April 2016, which taken by consecutive sampling method. The data analysis is intended to develop the value of calibration and discrimination.

Results : The final samples are 418, with 20.3 % incidence of kidney function deterioration. Odds Ratio of all predictors is similar with the result in VKPP study, except female variable which is not a risk factor (OR 0.78; 95% CI; 0,43-1,45). As final, the calibration and discrimination values are ​​0.594 and 0.568 (95% CI; 0.502-0.634). In the validation study, the incidence of WRF in the low, moderate, and high risk group which are calculated using VKPP consecutively valued 18.6 % , 21.9 % and 29.6 %. However, only the low-risk group who were in the range of probability predictions of WRF, which is 11-26 % (moderate and high risk valued 27 to 49.5 % and 50-80 %).

Conclusion : VKPP scoring system externally valid to predict low risk group.

 

Keywords     :  worsening renal function, acute decompensated heart failure, scoring system, external validation

 

Role of Pulse Pressure in Worsening Renal Function of Patient with Hypertension

Role of Pulse Pressure in Worsening Renal Function of Patient with Hypertension

 

Cardiovascular Risk Factors until End of Life

Risk factors until end of life

 

Predictive Value of Cardiac MRI After STEMI

Predictive Value of Cardiac MRI After STEMI

Role of Late Enhancement

Irnizarifka, MD.

Resident of Departement of Cardiology and Vascular Medicine

Faculty of Medicine, Universitas Indonesia

ABSTRACT

Background: Cardiovascular diseases are currently the leading cause of and are expected to become so in emerging countries by 2020. Among these, CAD is the most prevalent manifestation and is associated with high mortality and morbidity. Nowadays, at least 70% of patients hospitalized with AMI survive the acute hospital phase. Unfortunately, after STEMI, patients who develop heart failure carry worse prognosis. Strategies for the earliest possible risk assessment after STEMI have become essential not only to better target therapies but also to introduce these therapies in the timeliest manner while benefits still be greatest and to monitor the effects of therapy.

Objectives: This case report aimed to review a case of autolysis acute STEMI and discuss the role of Late Enhancement to predicts further cardiovascular risk.

Case Illustration: A fifty-three years old male was referred to the Emergency Department of NCCHK after 11 hours chief complaint of typical chest pain. He was previously diagnosed with acute STEMI at Sari Asih hospital. Occasionally there were no ST segment changes on admission at NCCHK, but his cardiac enzymes were elevated. He underwent coroangiography with the result of total occlusion at LCx. T2W-STIR revealed myocardial edema with total volume of 38% whereas LGE exhibited necrotic tissue at inferolateral wall from apex to base, with transmurality of 70%, necrotic volume of 20%, and late MVO.

Discussion: As a promising non-invasive imaging tool, CE-MRI provides more information such as infarct size, AAR, myocardial viability, MVO, and myocardial hemorrhage. Hence, lately it was associated with predictive value for outcomes. Available data suggest that LGE quantification very early during STEMI predicts late heart failure and adverse events beyond several traditional risk factors. A second major finding is that during the hyperacute phase of STEMI, LGE volume incurred the strongest association to LV function change. Alternate approaches including the assessment of late MVO which is prognostic marker for combined clinical endpoints after STEMI.

Keywords : acute STEMI, contrast-enhanced MRI, LGE, prognostic.

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Acute coronary syndrome represents the clinically manifest acute myocardial ischemia. Acute ischemia is usually, but not always, caused by atherosclerotic plaque rupture, fissuring, erosion, or a combination with superimposed intracoronary thrombosis, and is associated with an increased risk of cardiac death and myonecrosis.^{5, 6} Nowadays, at least 70% of patients hospitalized with acute myocardial infarction (AMI) survive the acute hospital phase.⁷ Despite optimal contemporary invasive and medical treatment, the coronary event rate in patients with ACS remains increased, compared with patients with stable symptoms. Growing evidence suggest that this phenomenon could be a consequence of multiple destabilized and vulnerable plaques throughout the coronary tree.⁸

Timely diagnosis of STEMI is a key to successful management. A 12-lead ECG must be performed as soon as possible to establish the diagnosis. The diagnosis of STEMI is based on any two of (1) typical chest pain, (2) ECG changes or new LBBB and (3) raised myocardial biomarkers.^{5, 9} ECG monitoring also should be initiated as soon as possible in all patients with suspected STEMI to detect life-threatening arrhythmias and allow prompt defibrillation if indicated. Typically, ST-segment elevation in acute myocardial infarction, measured at the J point, should be found in two contiguous leads and be ≥0.25 mV in men below the age of 40 years, ≥ 0.2 mV in men over the age of 40 years, or ≥0.15 mV in women in leads V2–V3 and/or ≥ 0.1 mV in other leads (in the absence of left ventricular (LV) hypertrophy or left bundle branch block (LBBB).⁹

Markers of myocardial necrosis are useful in corroborating the diagnosis, so it must be emphasized that they may not be elevated early after the onset of symptoms. Cardiac troponin (CTn) is the biomarker of choice because it is the most sensitive and specific marker of myocardial injury/necrosis available. Troponin levels usually increase after 3-4 hours.⁵ Troponin level may remain elevated up to 2 weeks. Elevated CTn values signal a higher acute risk and an adverse long term prognosis.¹⁰ Creatine Kinase Myocardial Band (CKMB) is less sensitive and specific. However, it remains useful for the diagnosis of early infarct extension (reinfarction) and peri-procedural MI because of its short half life.⁵ The level of CKMB and CTn at administration was elevated.

Acute MI has variable impact on long-term survival. After STEMI, patients who develop heart failure carry worse prognosis. Potential benefits might arise from earlier prediction and initiation of preventive treatment for heart failure during STEMI.³ Strategies for the earliest possible risk assessment after STEMI have become essential not only to better target therapies but also to introduce these therapies in the timeliest manner while benefits still be greatest and to monitor the effects of therapy.^{3, 4}

If in spite of angiography performed in the acute phase at the time of PCI there are concerns about inducible ischaemia in the infarct or non-infarct area, outpatient exercise testing (bicycle or treadmill) or stress imaging (using scintigraphy, echocardiography, or MRI) within 4–6 weeks is appropriate. LV dysfunction after STEMI may be due to necrosis, to stunning of viable myocardium remaining in the infarct territory, to hibernation of viable myocardium, or to a combination of all three. Simple stunning should usually recover within 2 weeks of the acute ischaemic insult if reperfusion has been established, but, if ischaemic episodes persist, recurrent stunning may become hibernation and requires revascularization for recovery of function. Hence, several diagnostic techniques can detect myocardial viability, especially MRI.¹

Myocardial oedema in the acute phase of myocardial infarction can be visualized as a bright signal on T2-weighted images, defining ‘myocardium at risk’. The major advantages of this technique are to distinguish chronic from acute infarction and to quantify the proportion of myocardial salvaged by comparing T2-weighted oedematous size and late enhancement images.¹¹ This case showed myocardial edema at anteroseptal and inferoseptal wall. Meanwhile, LGE images are T1-weighted inversion recovery sequences acquired about 10 min after intravenous administration of gadolinium. Gadolinium enhances its distribution volume in certain conditions such as necrotic or fibrotic myocardium (hyperenhancement). ¹¹

However, LVEF assessment performed very early after STEMI does not reliably predict late heart failure, because of heterogeneous LV remodeling and healing. LGE measured by cardiac MRI identifies necrosis burden in the chronic phase after MI. In this context, LGE predicts functional recovery after revascularization. However, suggestions of “infarct shrinkage” observed between the first week after infarction and later follow-up has raised the concern that LGE might not accurately assess myocardial damage due to overestimation in the very early STEMI period, because it might represent a combination of necrosis and edema comprising the area at risk. Alternate strategies including the assessment of late MVO and myocardial salvage have been proposed.³ Early and late MVO assessed by MRI are prognostic markers for combined clinical endpoints after STEMI.¹¹ This case showed late MVO embedded inside the necrotic tissue at LGE sequential of cardiac MRI.

Microvascular cell damage causes leakage of blood out of the injured vessel and the subsequent healing process is characterized by haemoglobin degradation in which dark areas on post-contrast sequences indicate not only the presence of microvascular obstruction, but also of intramyocardial haemorrhage. The extent of the hemorrhagic area correlates with the size of ‘dark zones’ on LGE sequences.¹¹

As a promising non-invasive imaging tool, CE-MRI can detect the pathological consequences of reperfusion strategies in vivo and provide more information such as infarct size, myocardial AAR, myocardial viability, MVO, and myocardial hemorrhage. Findings by Jiangqiang et al in 2012 added some knowledges in which the median infarct size was significantly smaller in the NSTEMI group than in the STEMI group (10.7% [5.6–18.1] vs. 19.2% [10.3–30.7], P<0.001). The NSTEMI group also had a significantly lower extent of microvascular obstruction and a smaller number of segments with >75% of infarct transmurality relative to the STEMI group (0% [0–0.6] vs. 0.9% [0–2.3], P<0.001 and 3.0 ± 2.3 vs. 4.6 ± 2.9, P = 0.001, respectively). Myocardial hemorrhage was detected less frequently in the NSTEMI group than the STEMI group (22.6% vs. 43.8%, P = 0.029).²

Another research by Larose et al discovered that LGE quantification very early during STEMI predicts late heart failure and adverse events beyond traditional risk factors such as infarct territory, maximum CK-MB rise, pain-to-balloon time, presence of Q waves, and LVEF during STEMI. A second major finding is that, during the hyperacute phase of STEMI, LGE volume incurred the strongest association to LV function change, beyond infarct transmurality, MVO, and salvaged myocardium (SM).³ IS within 1 week from AMI was directly related to LV remodelling and was a stronger predictor of future events than measures of LV systolic performance. The occurrence of LV dysfunction at 6 months increased with greater LGE: a cut-off of ≥ 23% LGE measured on hyperacute MRI showed the best accuracy for late LV dysfunction (sensitivity 89%, specificity 74%). In the assessment of myocardial viability in AMI patients, when the extent of LGE is <50% the likelihood for functional recovery is efficient.¹² This patient had 20% LGE volume so the possibility of LV dysfunction in the near future is low, but the likelihood for functional recovery was decreased since the necrosis transmurality was 70%.

 

SUMMARY

A fifty-three years old male was reported of having 11 hours chief complaint of typical chest pain. He was presented with non-ST segment elevation ECG after prior inferior ST segments elevation. There was elevation of cardiac enzymes. He underwent coroangiography which revealed total occlusion at LCx. CE-MRI was done and showed sign of sign of stress-inducible ischemia at inferolateral, septal, anterior walls and sign of acute myocardial infarction with late MVO at the same area.

This case report emphasizes the promising non-invasive imaging tool, CE-MRI, in providing more information such as infarct size, AAR, myocardial viability, MVO, and myocardial hemorrhage. This modality can be use to detect residual ischemia at culprit lesion, stress-inducible ischemia of remote lesion, infarct size, and late MVO.  Available data suggest that LGE quantification very early during STEMI predicts late heart failure and adverse events beyond traditional risk factors such as infarct territory, maximum CK-MB rise, pain-to-balloon time, presence of Q waves, and LVEF during STEMI. Another major finding is that, during the hyperacute phase of STEMI, LGE volume incurred the strongest association to LV function change, beyond infarct transmurality, MVO, and salvaged myocardium (SM). Late MVO assessed by MRI also become prognostic markers for combined clinical endpoints after STEMI.

 

REFERENCES

1.      Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. European heart journal. 2008; 29(23): 2909-45.

2.      Xu J, Song YB, Hahn JY, Chang SA, Lee SC, Choe YH, et al. Comparison of magnetic resonance imaging findings in non-ST-segment elevation versus ST-segment elevation myocardial infarction patients undergoing early invasive intervention. The international journal of cardiovascular imaging. 2012; 28(6): 1487-97.

3.      Larose E, Rodes-Cabau J, Pibarot P, Rinfret S, Proulx G, Nguyen CM, et al. Predicting late myocardial recovery and outcomes in the early hours of ST-segment elevation myocardial infarction traditional measures compared with microvascular obstruction, salvaged myocardium, and necrosis characteristics by cardiovascular magnetic resonance. Journal of the American College of Cardiology. 2010; 55(22): 2459-69.

4.      Berman DS, Hachamovitch R, Shaw LJ, Friedman JD, Hayes SW, Thomson LE, et al. Roles of nuclear cardiology, cardiac computed tomography, and cardiac magnetic resonance: Noninvasive risk stratification and a conceptual framework for the selection of noninvasive imaging tests in patients with known or suspected coronary artery disease. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2006; 47(7): 1107-18.

5.      Daga LC, Kaul U, Mansoor A. Approach to STEMI and NSTEMI. The Journal of the Association of Physicians of India. 2011; 59 Suppl: 19-25.

6.      Kristensen TS, Kofoed KF, Kuhl JT, Nielsen WB, Nielsen MB, Kelbaek H. Prognostic implications of nonobstructive coronary plaques in patients with non-ST-segment elevation myocardial infarction: a multidetector computed tomography study. Journal of the American College of Cardiology. 2011; 58(5): 502-9.

7.      Mulia E, Wicaksono SH, Kasim M. Role of Cardiac MRI in Acute Myocardial Infarction. Medical journal indonesia. 2013; 22(1): 46-53.

8.      Terkelsen CJ, Lassen JF, Norgaard BL, Gerdes JC, Jensen T, Gotzsche LB, et al. Mortality rates in patients with ST-elevation vs. non-ST-elevation acute myocardial infarction: observations from an unselected cohort. European heart journal. 2005; 26(1): 18-26.

9.      Taylor J. 2012 ESC Guidelines on acute myocardial infarction (STEMI). European heart journal. 2012; 33(20): 2501-2.

10.    Thygesen K, Mair J, Katus H, Plebani M, Venge P, Collinson P, et al. Recommendations for the use of cardiac troponin measurement in acute cardiac care. European heart journal. 2010; 31(18): 2197-204.

11.    de Waha S, Desch S, Eitel I, Fuernau G, Zachrau J, Leuschner A, et al. Impact of early vs. late microvascular obstruction assessed by magnetic resonance imaging on long-term outcome after ST-elevation myocardial infarction: a comparison with traditional prognostic markers. European heart journal. 2010; 31(21): 2660-8.

12.    Perazzolo Marra M, Lima JA, Iliceto S. MRI in acute myocardial infarction. European heart journal. 2011; 32(3): 284-93.

 

Hipertensi pada Sindroma Nefrotik Pediatrik

HIPERTENSI PADA SINDROMA NEFROTIK PEDIATRIK

Irnizarifka, MD.

Resident at Dept. of Cardiology and Vascular Medicine

Faculty of Medicine, Universitas Indonesia

Sindroma nefrotik (SN) pada anak merupakan penyakit ginjal anak yang paling sering ditemukan. Insidensi SN pada anak dalam kepustakaan di Amerika Serikat dan Inggris berkisar antara 2-7 per 100.000 anak dengan prevalensi antara 12-16 per 100.000 anak. Angka tersebut tercatat lebih tinggi pada Negara berkembang. Di Indonesia dilaporkan 6 per 100.000 per tahun anak berusia kurang dari 14 tahun mengalami SN dengan perbandingan anak laki-laki dan perempuan 2:1. SN sendiri didefinisikan sebagai keadaan klinis yang ditandai dengan gejala proteinuria masif (> 40 mg/m² LPB/jam atau 50 mg/kgBB/hari atau rasio protein/kreatinin pada urin sewaktu > 2 atau dipstik ≥ 2+), hipoalbuminemia < 2,5 mg/dL, edema, serta dapat disertai dengan hiperkolesterolemia > 200 mg/dL. SN idiopatik adalah kombinasi antara sindroma nefrotik dan kelainan histologis nonspesifik termasuk kelainan minimal, fokal segmental glomerulosklerosis maupun proliferasi mesangial difus.

Terdapat beberapa definisi terkait dengan SN. Remisi adalah proteinuria negatif atau trace (proteinuria < 4 mg/m² LPB/ jam) selama 3 hari berturut-turut dalam 1 minggu. Relaps adalah proteinuria ≥ 2+ (proteinuria ≥ 40 mg/m² LPB/jam) selama 3 hari berturut-turut dalam 1 minggu. Relaps jarang adalah relaps kurang dari 2x dalam 6 bulan pertama setelah respon awal atau kurang dari 4x per tahun pengamatan. Relaps sering (relaps frekuen) adalah relaps ≥ 2x dalam 6 bulan pertama setelah respon awal atau ≥ 4x dalam periode 1 tahun. Dependen steroid adalah relaps 2x berurutan pada saat dosis sterois diturunkan (alternating) atau dalam 14 hari pengobatan dihentikan. Resisten steroid didefinisikan sebagai tidak terjadinya remisi pada pengobatan prednison dosis penuh (full dose) 2 mg/kgBB/hari selama 4 minggu. Sensitif steroid adalah remisi terjadi pada pemberian prednison dosis penuh selama 4 minggu.

Kelainan penyebab terjadinya SN hanya teridentifikasi kurang dari 5 %, termasuk diantaranya adalah sistemik lupus eritematosus, Henoch Schonlein Purpura, amiloidosis dan infeksi HIV, parvovirus B19 serta virus hepatitis B dan C. Terdapat bukti epidemiologi bahwa insidensi sindroma nefrotik lebih tinggi di Asia Selatan. Indian Amerika, Hispanik, dan Amerika keturunan Afrika memiliki insidensi yang lebih tinggi dibandingkan dengan kulit putih. SN glomeruloskelosis juga lebih banyak ditemukan pada anak-anak Amerika keturunan Afrika dibandingkan dengan kulit putih.

SN idiopati atau primer merupakan bentuk yang paling sering ditemukan. Lesi glomerular yang dihubungkan dengan SN idiopatik termasuk kelainan minimal, fokal segmental glomerulosklerosis, glomerulonefritis membranoproliferatif, nefropati membranosa dan proliferasi mesangial difus. Beberapa sindroma nefrotik yang diturunkan disebabkan karena mutasi gen-gen yang mengkode komponen protein utama pada aparatus filtrasi glomerular. Gambaran klinis utama pasien dengan SN adalah adanya edema palpebral atau pretibial. Bila lebih berat akan disertai asites, efusi pleura dan edema skrotum. Keseluruhan gambaran klinis tersebut kadang-kadang disertai oliguria dan gejala infeksi, nafsu makan berkurang ataupun diare. Dalam laporan oleh ISKDC (International Study of Kidney Diseases in Children), pada SNKM ditemukan 22% disertai dengan hematuria mikroskopik, 15-20% hipertensi dan 32% peningkatan kadar kreatinin dan ureum darah yang bersifat sementara.

Klasifikasi SN berdasarkan gambaran histopatologis, dibagi dalam sindroma nefrotik kelainan minimal (SNKM), yang merupakan bagian besar (80%) dari SN idiopatik, dan sindroma nefrotik kelainan non minimal (SNKNM). Diantara SNKNM, bentuk glomeruloskerosis fokal segmental (GSFS) merupakan yang terbanyak pada anak (sekitar 7-8%), diikuti dengan 4-6% glomerulonefritis membranoproliferatif (GNMP) dan 1,5% nefropati membranosa (GNM). Klasifikasi SN lain adalah berdasarkan etiologi. Sebagian besar SN pada anak bersifat primer, idiopatik, sedangkan sebagian kecil adalah SN sekunder yang etiologinya berasal dari penyakit sistemik di luar ginjal, seperti lupus eritematosus sistemik (SLE) dan Henoch Schonlein Purpura. Bentuk yang lebih jarang adalah SN kongenital (Finnish type) yang terjadi sebelum usia 3 bulan dan disebabkan kelainan genetik, yakni adanya mutasi gen NPHS1 pada kromosom 19q13.1.

Manifestasi klinis SN terutama disebabkan oleh proteinuria, karenanya proteinuria dianggap sebagai kelainan primer. Gejala klinis lain dan hasil laboratorium dianggap sebagai manifestasi sekunder. Proteinuria pada SN bersifat masif, sehingga berbeda dari proteinuria lain yang tidak disebabkan oleh SN. Dikatakan proteinuria masif apabila ekskresi protein > 40 mg/jam/m² luas permukaan tubuh. Jenis protein yang hilang bervariasi tergantung dari lesi pada glomerulus. Pada SNKM, protein yang hilang sebagian besar adalah albumin sehingga disebut sebagai proteinuria selektif, sedangkan pada jenis lesi SN lainnya protein yang hilang adalah campuran albumin dan protein dengan berat molekul yang lebih besar sehingga disebut sebagai proteinuria nonselektif. Pada anak dengan SN, sintesis albumin dalam keadaan normal atau meningkat, namun hal tersebut tidak cukup untuk mengkompensasi kehilangannya karena lolos dalam proses filtrasi glomerulus. Jumlah albumin yang didegradasi biasanya dibawah normal, meskipun hal ini bersifat relatif terhadap kadar albumin intravaskuler karena katabolisme fraktional meningkat melalui mekanisme peningkatan katabolisme albumin di tubulus ginjal dan penurunan katabolisme ekstrarenal. Hal inilah yang kemudian akan berperan dalam terjadinya edema.

Pemeriksaan penunjang yang dapat dilakukan antara lain urinalisis yang disertai biakan urin bila ditemukan gejala klinis yang mengarah kepada infeksi saluran kemih, pemeriksaan protein urin kuantitatif dengan menggunakan urin 24 jam atau rasio protein/kreatinin pada urin pertama pagi hari, serta pemeriksaan darah yang terdiri atas darah tepi lengkap, albumin dan kolesterol serum, ureum, kreatinin, klirens kreatinin, serta kadar komponen C3, ANA dan anti ds-DNA bila dicurigai adanya SLE sebagai penyebab utama.

Proteinuria terjadi akibat adanya perubahan pada kapiler gomerulus dan pada umumnya tergantung  pada jenis lesinya. Pada SNKM didapatkan penurunan klirens protein bermuatan netral tapi peningkatan klirens protein bermuatan negatif seperti albumin. sehingga dianggap bahwa proses ini adalah akibat hilangnya barier muatan negatif. Heparan sulfat proteoglikan yang terdapat pada lamina rara eksterna dan interna menyebabkan timbulnya muatan negatif dan merupakan penghalang utama terhadap keluarnya molekul bermuatan negatif seperti albumin.  Penurunan heparan sulfat proteoglikan dengan heparitinase menyebabkan terjadinya albuminuria. Pada sel epitel terdapat terdapat sialoprotein glomerulus, suatu polianion yang memberikan muatan negatif pada sel epitel. Pada SNKM jumlah sialoprotein kembali normal setelah pemberian steroid, sedangkan pada SN akibat proliferatif glomerulonefritis atau diabetes melitus, klirens molekul kecil menurun dan klirens molekul besar meningkat, hal ini menunjukan adanya perubahan pada pori baik ukuran, jumlah ataupun keduanya.

Edema merupakan gejala kardinal pada SN. Mekanisme terjadinya edema dapat dijelaskan melalui dua teori, yaitu Teori Underfill dan Overfill/overflow. Teori Underfill adalah teori klasik mengenai pembentukan edema, yakni menurunnya tekanan onkotik intravaskular yang menyebabkan cairan merembes ke ruang interstitial. Dengan meningkatnya permeabilitas glomerulus, albumin akan keluar dan kemudian menimbulkan albuminuria dan hipoalbuminemia. Hipoalbuminemia menyebabkan menurunnya tekanan onkotik koloid plasma intravaskular. Keadaan ini menyebabkan meningkatnya cairan transudat melewati dinding kapiler dari ruang intravaskuler ke ruang interstisial yang menyebabkan edema. Sebagai akibat dari pergeseran cairan ini, volume plasma total dan volume darah arteri dalam peredaran menurun dibanding dengan volume sirkulasi efektif. Menurunnya volume plasma atau volume sirkulasi efektif merupakan stimulasi timbulnya retensi air dan natrium renal. Retensi natrium dan air ini timbul sebagai usaha tubuh untuk menjaga volume dan tekanan intravaskular agar tetap normal dan dapat dianggap sebagai peristiwa kompensasi sekunder. Retensi cairan yang secara terus menerus menjaga volume plasma selanjutnya akan mengencerkan protein plasma dan demikian menurunkan tekanan onkotik plasma dan akhirnya mempercepat gerak cairan masuk ke ruang interstisial. Keadaan ini akan terus memperberat edema sampai terdapat keseimbangan hingga edema stabil.

Teori overflow/overfill menunjukkan meningkatnya volume plasma dengan tertekannya aktivitas renin plasma dan kadar aldosteron. Retensi natrium renal dan air terjadi karena mekanisme intrarenal primer dan tidak bergantung pada stimulasi sistemik perifer. Retensi natrium renal primer mengakibatkan ekspansi volume plasma dan cairan ekstraselular. Pembentukan edema terjadi sebagai akibat dari perpindahan cairan ke dalam ruang interstisial. Teori ini dapat menerangkan adanya volume plasma yang tinggi dengan kadar renin plasma dan aldosteron yang menurun sekunder terhadap hipervolemia.

Anak dengan manifestasi klinis SN pertama kali, sebaiknya dirawat di rumah sakit dengan tujuan untuk mempercepat pemeriksaan dan evaluasi pengaturan diit, penanggulangan edema, memulai pengobatan steroid dan edukasi orang tua. Prinsip utama pemberian steroid adalah dengan penyesuaian pada berat badan disertai pengukuran tekanan darah dan pencarian fokus infeksi terutama gigi-geligi, telinga dan kecacingan. Tirah baring tidak perlu dipaksakan dan aktivitas fisik disesuaikan dengan kemampuan pasien. Bila edema cenderung tidak berat, maka anak diperbolehkan untuk kembali sekolah.

Bila didapatkan gejala atau tanda yang merupakan kontraindikasi terhadap steroid, seperti tekanan darah tinggi, peningkatan ureum dan/atau kreatinin dan infeksi berat, maka dapat diberikan sitostatik CPA oral maupun CPA puls. Siklofosfamid dapat diberikan per oral dengan dosis 2-3 mg/kgBB/hari dosis tunggal, selama 8 minggu maupun secara intravena (CPA puls) dengan dsis 500-750 mg/m² LPB yang dilarutkan dalam 250 mL laruran NaCl 0,9% selama 2 jam. CPA puls diberikan sebanyak 7 dosis dengan interval 1 bulan (total durasi pemberian adalah 6 bulan).

Hipertensi merupakan salah satu komplikasi dari SN yang dapat ditemukan baik pada awitan penyakit ataupun dalam perjalanan penyakit akibat toksisitas steroid. Pemberian steroid jangka panjang sendiri dapat menimbulkan efek samping yang signifikan terhadap penderita. Dengan demikian edukasi terhadap penderita dan orang tuanya menjadi sangat penting. Pengobatan hipertensi diawali dengan inhibitor ACE-i (Angiotensin Converting Enzyme inhibitors), ARB (Angiotensin Receptor Blocker), CCB (Calcium Channel Blockers), atau antagonis β adrenergik, hingga tekanan darah anak di bawah persentil 90. Pada semua pasien rawat jalan SN dengan pengobatan steroid, maka harus dilakukan pemantauan tekanan darah setiap 6 bulan sekali.

Tidak berbeda dengan kasus Chronic Kidney Disease (CKD), tujuan mengontol tekanan darah pada kasus SN ini adalah untuk memproteksi risiko lanjutan kardiovaskular dan menunda penurunan Glomerular Filtration Rate (GFR) yang progresif. Hingga saat ini belum ditemukan bukti spesifik tentang kepentingan tekanan sistolik ataupun diastolik dalam manajemen kontrol hipertensi pada kasus SN. Kontrol tekanan darah pada pasien anak dengan SN akan menjadi lebih baik bila berada di bawah persentil 50 tekanan darah sesuai usia dan jenis kelamin. Terapi menggunakan ACE-i atau ARB tetap menjadi lini pertama hipertensi pada kasus SN.

Terapi ACE-i dan ARB telah banyak digunakan untuk mengurangi proteinuria. Cara kerja kedua obat ini dalam menurunkan ekskresi protein di urin melalui penurunan tekanan hidrostatis untuk mengubah permeabilitas glomerulus. ACE-i juga memiliki efek renoprotektor melalui penurunan sintesis transforming growth factor (TGF)-β1 dan plasminogen activator inhibitor (PAI)-1 yang keduanya merupakan sitokin penting yang berperan dalam terjadinya glomerulosklerosis. Golongan ACE-i yang dapat digunakan antara lain captopril 0,3 mg/kgBB diberikan 3xsehari, enalapril 0,5 mg/kgBB/hari dibagi dalam 2 dosis, lisinopril 0,1 mg/kgBB dosis tunggal. Golongan ARB yang dapat digunakan hanya losartan 0,75 mg/kgBB dosis tunggal.

Prognosis jangka panjang SNKM selama pengamatan selama 20 tahun menunjukkan hanya sekitar 4-5% berujung pada gagal ginjal terminal, sedangkan 25% GSFS akan menjadi gagal ginjal terminal dalam 5 tahun. Pada penelitian jangka panjang ternyata respons terhadap pengobatan steroid lebih sering digunakan untuk menentukan prognosis dibandingkan dengan gambaran patologi anatomi.

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