The role of tolvaptan add-on therapy in patients with acute heart failure: a systematic review and network meta-analysis.

Background: Several conflicting reviews have concluded that the use of loop diuretics is associated with poorer clinical and safety outcomes. Therefore, this study aimed to investigate the efficacy and safety of tolvaptan as an adjunct to conventional diuretic therapy in patients with acute heart failure (AHF). Methods: A comprehensive search was conducted on PubMed, Embase, ProQuest, EBSCO, and Cochrane Library until 24 May 2023 to identify randomized controlled trials that compared the effects of tolvaptan with conventional therapy and placebo in patients with AHF. The quality assessment of the included trials was conducted using the Cochrane risk of bias. A network meta-analysis (NMA) was conducted to examine the dosage effect of tolvaptan. Result: A total of 17 studies with 18 reports, involving 10,039 patients, were selected. The tolvaptan add-on therapy significantly alleviated dyspnea [24 h: RR 1.16 (1.04, 1.29), 48 h: RR 1.18 (1.04, 1.33)], reduced body weight within 48 h [Asian group, MD -0.93 (-1.48, -0.38); non-Asian group, MD -2.76 (-2.88, -2.65)], reduced edema [RR 1.08 (1.02, 1.15)], increased serum sodium [non-Asian group, MD 3.40 (3.02, 3.78)], and resulted in a change in serum creatinine [MD -0.10 (-0.18, -0.01)]. No significant differences were observed in mortality and rehospitalization. The NMA suggested that an intermediate dosage (15 mg/day) might offer the best efficacy in reducing dyspnea within 24 h, reducing edema, increasing serum sodium, and lowering the incidence of worsening renal function (WRF). Conclusion: In conclusion, the meta-analysis showed that tolvaptan contributed to the short-term alleviation of congestive symptoms, elevated sodium levels, and a lower incidence of WRF. However, no significant benefits were observed in long-term symptoms, rehospitalization rates, and mortality. An intermediate dosage of tolvaptan might be considered the optimal choice for various clinical outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42023420288).

The Risk Factors of Mitral Regurgitation Deterioration After Secundum Atrial Septal Defect Closure.

Background: Association between secundum Atrial Septal Defect (ASD) and mitral valve (MV) disease has been recognized for decades. Secundum ASD closure can reduce mitral regurgitation (MR) degree. However, in some patients, deterioration of MR after ASD closure has been observed. We aimed to identify the risk factors of MR deterioration after ASD closure. Methods: This was an observational retrospective cohort study. Data were collected from the registry and echocardiogram report. We evaluated all patients with ASD closure by surgery and transcatheterization without MR intervention from January 2012 until June 2021 at Dr. Sardjito General Hospital, Yogyakarta. We excluded patients with multiple ASD and ASD with severe MR requiring MV intervention. Risk factors for MR deterioration were evaluated using multivariate logistic regression. Results: A total of 242 patients who underwent post-secundum ASD closure were included. In multivariate analysis, ASD closure by surgery, large left atrial (LA) diameter (>40 mm), low left ventricular ejection fraction (LVEF; <55%), and MV regurgitation degree were significant risk factors for MR worsening after ASD closure, with OR of 2.103 (95% CI 1.124-3.937); 2.871 (95% CI 1.032-7.985); 5.531 (95% CI 1.368-22.366); and 2.490 (95% CI 1.339-4.630) respectively. Conclusion: ASD closure by surgery, large LA diameter (>40 mm), low LVEF (<55%), and MV regurgitation degree are independent significant risk factors for MR deterioration in post-secundum ASD closure patients. In adult ASD patients with reduced LV function, it is recommended to perform balloon testing and consider fenestrated closure, as low LVEF <55% has the highest risk of causing new or deteriorating MR.

Effectiveness of Dexmedetomidine as Myocardial Protector in Children With Classic Tetralogy of Fallot Having Corrective Surgery: A Randomized Controlled Trial.

OBJECTIVES: Efficacy of dexmedetomidine (DEX) as a cardioprotective agent in Indonesian children undergoing classic tetralogy of Fallot (TOF) repair with cardiopulmonary bypass (CPB). DESIGN: A prospective, parallel trial using block randomization along with double-blinded preparation of treatment agents by other parties. SETTING: National Cardiovascular Center Harapan Kita, Indonesia. PARTICIPANTS: Sixty-six children with classic TOF scheduled for corrective surgery. No children were excluded. All patients had fulfilled the criteria for analysis. INTERVENTIONS: A total of 0.5 µg/kg bolus of DEX was added to the CPB priming solution, followed by 0.25 µg/kg/h maintenance during bypass. The placebo group used normal saline. Follow-ups were up to 30 days. MEASUREMENTS AND MAIN RESULTS: Troponin I was lower in the DEX group at 6 hours (30.48 ± 19.33 v 42.73 ± 27.16, p = 0.039) and 24 hours after CPB (8.89 ± 5.42 v 14.04 ± 11.17, p = 0.02). Within a similar timeframe, DEX successfully lowered interleukin-6 (p = 0.03; p = 0.035, respectively). Lactate was lower in the Dex group at 1, 6, and 24 hours after CPB (p < 0.01; p = 0.048; p = 0.035; respectively). Dexmedetomidine increased cardiac output and index from 6 hours after bypass, but vice versa in systemic vascular resistance. Reduction of vasoactive inotropic score was seen during intensive care unit monitoring in the Dex group (p = 0.049). Nevertheless, DEX did not significantly affect the length of ventilation (p = 0.313), intensive care unit stay (p = 0.087), and mortality (p > 0.99). CONCLUSIONS: Dexmedetomidine during CPB is an effective cardioprotective agent in TOF children having surgery. Postoperative mortality was comparable across groups.

Risk Factors Associated With Prolonged Mechanical Ventilation and Length of Stay After Repair of Tetralogy of Fallot.

BACKGROUND: This study examined preoperative, intraoperative, and postoperative data to identify factors that are associated with prolonged mechanical ventilation (PMV) and prolonged intensive care unit length of stay (ICU LOS) in tetralogy of Fallot (TOF) patients undergoing repair surgery. METHODS: A retrospective study was carried out after approval from the institutional review board. All patients (age 0-52 years) who underwent TOF repair from January 2016 to September 2022 were included. Prolonged mechanical ventilation was defined as >24 h of ventilation, while prolonged ICU LOS was defined as ICU stay >3 days. RESULTS: A total of 922 patients were included, among whom 288 (31.2%) were intubated for >24 h and 222 (24.1%) stayed in ICU for >3 days. Younger age (odds ratio [OR] = 2, 95% confidence interval [CI] 1.2-3.3, P = .007), lower weight (OR = 2.1, 95% CI 1.2-3.5, P = .003), and residual lesion (OR = 3.27, 95% CI 1.2-8.7, P = .017) were associated with PMV. Moreover, independent risk factors for prolonged ICU LOS are similar to PMV risk factors, including younger age (OR = 2.3, 95% CI 1.28-4.12, P = .005), lower weight (OR = 2.83, 95% CI 1.58-5, P < .001), underweight status (OR = 1.7, 95% CI 1.12-2.57, P = .012), and residual lesion (OR = 3.79, 95% CI 1.43-10.05, P = .007). Both aortic cross-clamp and cardiopulmonary bypass times did not exhibit clinically significant risk factors toward PMV and prolonged ICU LOS. CONCLUSIONS: The risk factors for PMV and prolonged ICU LOS were residual lesion, younger age, and lower weight. Nutritional status contributed to the risk of prolonged ICU LOS, but not PMV. Consideration of these factors may provide optimal care to improve the outcome following TOF corrective surgery.

Global Longitudinal Strain Right Ventricle (GLS RV) as a Predictor for Mean Pulmonary Artery Pressure (MPAP) on Secundum Atrial Septal Defect (ASD) with Pulmonary Hypertension.

Objectives: The objectives of the study were to determine the association between global longitudinal strain right ventricle (GLS-RV) and mean pulmonary artery pressure (mPAP) on secundum atrial septal defect (ASD) with pulmonary hypertension (PH). Methods: This study was an analytic observational with the cross-sectional approach. This study was conducted with secundum ASD patients who underwent right heart catheterization (RHC) from February 2019 to July 2019 at Sardjito General Teaching Hospital Yogyakarta. Demographic data were collected and echocardiographic parameters were evaluated based on the standard examination. The results were statistically analyzed using the correlation hypothesis test. If the data were normally distributed, the Pearson's correlation test was used, if the data were not normally distributed, Spearman's correlation test was used to analyze the correlation. Results: Thirty-four patients were enrolled in this study. There was strongly significant positive correlation between GLS-RV and mPAP found in patients with Secundum ASD (P = 0.0001, r = 90.5%). Conclusions: This is the first study in Indonesia that analyzed the association between GLS-RV and mPAP in Secundum ASD patients. There was a strongly significant positive correlation between GLS-RV and mPAP in patients with Secundum ASD after RHC. We assume that the association is influenced by progressivity and degree of disease severity.

An electrocardiographic score to predict pulmonary hypertension in children with atrial septal defect.

BACKGROUND: In limited resource settings, identification of factors that predict the occurrence of pulmonary hypertension(PH) in children with atrial septal defect(ASD) is important to decide which patients should be prioritized for defect closure to prevent complication. Echocardiography and cardiac catheterization are not widely available in such settings. No scoring system has been proposed to predict PH among children with ASD. We aimed to develop a PH prediction score using electrocardiography parameters for children with ASD in Indonesia. METHODS: A cross-sectional study reviewing medical record including ECG record was conducted among all children with newly diagnosed isolated ASD admitted to Dr Sardjito Hospital in Yogyakarta, Indonesia during 2016-2018. Diagnosis of ASD and PH was confirmed through echocardiography and/or cardiac catheterization. Spiegelhalter Knill-Jones approach was used to develop PH prediction score. Accuracy of prediction score was performed using a receiver operating characteristic (ROC) curve. RESULTS: Of 144 children, 50(34.7%) had PH. Predictors of pulmonary hypertension were QRS axis ≥120°, P wave ≥ 3 mm at lead II, R without S at V1, Q wave at V1, right bundle branch block (RBBB), R wave at V1, V2 or aVR > normal limit and S wave at V6 or lead I > normal limit. ROC curve from prediction scores yielded an area under the curve (AUC) 0.908(95% CI 0.85-0.96). Using the cut-off value 3.5, this PH prediction score had sensitivity of 76%(61.8-86.9), specificity 96.8%(91.0-99.3), positive predictive value 92.7%(80.5-97.5), negative predictive value 88.4%(82.2-92.6), and positive likelihood ratio 23.8(7.7-73.3). CONCLUSIONS: A presence of PH in children with ASD can be predicted by the simple electrocardiographic score including QRS axis ≥120°, P wave ≥3 mm at lead II, R without S at V1, Q wave at V1, RBBB, R wave at V1, V2 or aVR > normal limit and S wave at V6 or lead I > normal limit. A total score ≥ 3.5 shows a moderate sensitivity and high specificity to predict PH among children with ASD.

Prognostic Value for Mortality of Plasma Bioactive Adrenomedullin in Patients with Pulmonary Arterial Hypertension: A Sub Analysis of the Biomarker Study in the COHARD-PH Registry.

The adrenomedullin level increases in pulmonary arterial hypertension (PAH, and correlates with a high mortality rate. Its active form, bioactive adrenomedullin (bio-ADM), has been recently developed and has significant prognostic applications in acute clinical settings. Aside from idiopathic/hereditary PAH (I/H-PAH), atrial septal defects-associated pulmonary artery hypertension (ASD-PAH) is still prevalent in developing countries and associated with increased mortality. This study aimed to investigate the mortality-wise prognostic value of the plasma bio-ADM level by comparing subjects with ASD-PAH and I/H-PAH with ASD patients without pulmonary hypertension (PH) as a control group. This was a retrospective, observational cohort study. The subjects were Indonesian adult patients who were recruited from the Congenital Heart Disease and Pulmonary Hypertension (COHARD-PH) registry and divided into three groups: (1) ASD without PH (control group), (2) ASD-PAH and (3) I/H-PAH. During right-heart catheterization at the time of diagnosis, a plasma sample was taken and assayed for bio-ADM using a chemiluminescence immunoassay. Follow-up was performed as a part of the COHARD-PH registry protocol in order to evaluate the mortality rate. Among the 120 subjects enrolled: 20 turned out to have ASD without PH, 85 had ASD-PAH and 15 had I/H-PAH. Compared to the control group (5.15 (3.0-7.95 pg/mL)) and ASD-PAH group (7.30 (4.10-13.50 pg/mL)), bio-ADM levels were significantly higher in the I/H-PAH group (median (interquartile range (IQR)): 15.50 (7.50-24.10 pg/mL)). Moreover, plasma bio-ADM levels were significantly higher in subjects who died (n = 21, 17.5%) compared to those who survived (median (IQR): 11.70 (7.20-16.40 pg/mL) vs. 6.90 (4.10-10.20 pg/mL), p = 0.031). There was a tendency toward higher bio-ADM levels in those who died among the PAH subjects, in both ASD-PAH and I/H-PAH groups. In conclusion, the plasma bio-ADM level is elevated in subjects with PAH from both ASD-PAH and I/H-PAH origins, reaching the highest levels in subjects with the I/H-PAH form. A high bio-ADM level tended to be associated with a high mortality rate in all subjects with PAH, indicating a relevant prognostic value for this biomarker. In patients with I/H-PAH, monitoring bio-ADM could represent a valid tool for predicting outcomes, allowing more appropriate therapeutical choices.

NKX2-5 variants screening in patients with atrial septal defect in Indonesia.

BACKGROUND: NKX2-5 variant in atrial septal defect patients has been reported. However, it is not yet been described in the Southeast Asian population. Here, we screened the NKX2-5 variants in patients with atrial septal defect (ASD) in the Indonesian population. METHOD: We recruited 97 patients with ASD for genetic screening of the NKX2-5 variant using Sanger sequencing. RESULTS: We identified three variants of NKX2-5: NM_004387.4:c.63A>G at exon 1, NM_004387.4:c.413G>A, and NM_004387.4:c.561G>C at exon 2. The first variant is commonly found (85.6%) and benign. The last two variants are heterozygous at the same locus. These variants are rare (3.1%) and novel. Interestingly, these variants were discovered in familial atrial septal defects with a spectrum of arrhythmia and severe pulmonary hypertension. CONCLUSION: Our study is the first report of the NKX2-5 variant in ASD patients in the Southeast Asian population, including a novel heterozygous variant: NM_004387.4:c.413G>A and NM_004387.4:c.561G>C. These variants might contribute to familial ASD risk with arrhythmia and severe pulmonary hypertension. Functional studies are necessary to prove our findings.

Usefulness of Combining NT-proBNP Level and Right Atrial Diameter for Simple and Early Noninvasive Detection of Pulmonary Hypertension Among Adult Patients with Atrial Septal Defect.

BACKGROUND: Atrial septal defect developed pulmonary hypertension (ASD-PH) at first diagnosis due to late presentation are common in Indonesia. Transthoracic echocardiogram (TTE) is a common tool to detect ASD-PH, before proceeding to invasive procedure. The NT-proBNP measurement to screen ASD-PH is not yet considered the standard approach, especially in limited resource conditions. The objective of this study is to assess the value of NT-proBNP, along with simple TTE parameter, to screen PH among adults with ASD. METHODS: This was a cross-sectional study. The subjects were adult ASD-PH patients from the COHARD-PH  registry (n=357). Right heart catheterization (RHC) was performed to diagnose PH. Blood sample was withdrawn during RHC for NT-proBNP measurement. The TTE was performed as standard procedure and its regular parameters were assessed, along with NT-proBNP, to detect PH. RESULTS: Two parameters significantly predicted PH, namely NT-proBNP and right atrial (RA) diameter. The cut-off of NT-proBNP to detect PH was ≥140 pg/mL. The cut-off of RA diameter to detect PH was ≥46.0 mm. The combined values of NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm yielded 46.6% sensitivity, 91.8% specificity, 54.3% accuracy, 96.5% positive predictive value and 26.2% negative predictive value to detect PH, which were better than single value. CONCLUSION: NT-proBNP level ≥140 pg/mL represented PH in adult ASD patients. The NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm had a pre-test probability measures to triage patients needing more invasive procedure and also to determine when and if to start the PH-specific treatment.

Pulmonary Arterial Hypertension in Indonesia: Current Status and Local Application of International Guidelines.

Recent advances in the diagnosis and management of pulmonary arterial hypertension (PAH) have led to a significant improvement in the outcomes for patients with PAH. However, prompt and accurate diagnosis of PAH remains an unmet challenge due to lack of awareness and lack of meticulous data to profile the etiology and pathophysiology of this rare progressive disease, especially in low- and middle-income country. In Indonesia, the true prevalence and incidence of different subtypes of PAH in general population is still unknown. The Congenital HeARt Disease in adult and Pulmonary Hypertension (COHARD-PH) registry was the first single-center prospective registry in Indonesia, which indicated that almost 80% of adult patients with congenital heart disease (CHD) had experienced PAH and even Eisenmenger syndrome due to delayed diagnosis. Screening for early detection of asymptomatic CHD in children is yet to be systematically established in Indonesia, leading to undiagnosed and uncorrected CHD in adulthood. There are no specific national guidelines focusing on diagnostic workup and treatment of PAH in Indonesia. Furthermore, the lack of adequate diagnostic facilities, limited treatment availability, and limited drug coverage under the National Health Insurance Scheme are key issues that remain unaddressed. This review focuses on the diagnosis, treatment, and management of PAH associated with CHD in Indonesia as per international guidelines. We have proposed recommendations to effectively control and prevent PAH associated with CHD in Indonesia. The paper should be of interest to readers in the area of medical management and policy makers especially in low- and middle-income countries. Key Highlights: Pulmonary arterial hypertension (PAH) is a rare progressive subtype of pulmonary hypertension with poor overall prognosis and outcomes.Prompt and accurate diagnosis of PAH remains an unmet challenge in low- and middle-income countries due to poor knowledge about the etiology and pathophysiology of this syndrome. Also, the symptoms and signs of early-stage PAH are usually nonspecific or undetectable in newborn and infants, thus presenting a challenge for physicians to establish early diagnoses of PAH.The challenging factors in low- and middle-income countries, especially Indonesia archipelago are limitations of healthcare infrastructure, limited expertise, lack of awareness, lack of timely PAH screening strategies, poor antenatal care and unpredictable availability of PAH medications.There are no specific national guidelines focusing on diagnostic workup and treatment of PAH in Indonesia. Under-utilization of treatment guidelines and lack of adequate diagnostic treatment facilities have resulted in sub-optimal management of PAH patients in Indonesia.Adherence to international guidelines is an important aspect of PAH management in Indonesia. Updated disease and functional classifications of PAH as per international guidelines along with new research findings on prognostic factors can help in making better management decisions for PAH patients at different stages of the disease.

Remarkable response to pericardial window procedure and weekly docetaxel treatment in a metastatic breast cancer patient with pericardial effusion and cardiac tamponade.

Metastatic breast cancer may present as a pericardial effusion that can progress to a life-threatening cardiac tamponade. Pericardial window followed by initial chemotherapy needs to be immediately applied in order to achieve a favorable outcome.

The effect of oral sildenafil therapy on health-related quality of life in adults with pulmonary arterial hypertension related to uncorrected secundum atrial septal defect: a quasi experimental study.

BACKGROUND: Assessment of health-related quality of life (HRQoL) are often measured as an important patient-reported outcome (PRO) in clinical studies. Pulmonary arterial hypertension (PAH) is a common complication of atrial septal defect (ASD). This study aimed to compare the HRQoL of PAH related uncorrected secundum ASD at pre and post therapy with oral sildenafil therapy. METHODS: We conducted quasi experimental study at Sardjito General Hospital Yogyakarta since April 2016 to August 2017. Adults with PAH related uncorrected secundum ASD, listed on Congenital Heart Disease and Pulmonary Hypertension (COHARD-PH) registry, and met the inclusion and exclusion criteria were recruited as subject. Interview was done at pre and 12 weeks post oral sildenafil therapy 3 × 20 mg using the EQ-5D-3L questionnaire. Statistical analysis was done using Wilcoxon test and paired T-test to determine the differences of EQ-5D utility and EQ-VAS score at pre and post therapy. RESULTS: A total of 18 adult patients with PAH related to uncorrected secundum ASD were enrolled in this study (83.33% female; mean age 38.72 ± 10.81 years old). The most frequent reported problems pre therapy were pain/discomfort (83%) and anxiety/depression (78%). Wilcoxon test showed the median of EQ-5D utility score were increased after sildenafil therapy (before = 0.604, after = 0.664; Z = - 2703; p:0.007), respectively. Meanwhile, the paired T-test results showed an increase of EQ-VAS mean difference 6.67 ± 8.75 (p:0.005; 95% CI 2.32-11.02) after sildenafil therapy. CONCLUSION: The administration of oral sildenafil therapy 3 × 20 mg during 12 weeks in adult patients with PAH related uncorrected secundum ASD gives better HRQoL.

Profile of Endothelin-1, Nitric Oxide, and Prostacyclin Levels in Pulmonary Arterial Hypertension Related to Uncorrected Atrial Septal Defect: Results from a Single Center Study in Indonesia.

METHODS: The study design was cross-sectional. The subjects were adult uncorrected secundum ASD with PAH. Pulmonary artery pressure was measured with right heart catheterization. Pulmonary venous blood was obtained during catheterization for measuring endothelin-1, prostacyclin, and nitric oxide. Correlation tests were performed to determine any association between biomarkers and mean pulmonary artery pressure (mPAP). The levels of biomarkers were compared based on the severity of PAH. Statistical significance was determined at p < 0.05. RESULTS: Forty-four subjects were enrolled in this study. Endothelin-1 level and mPAP had significant moderate positive correlation (r = 0.423 and p value = 0.004). However, no significant correlation was observed between prostacyclin, nitric oxide levels, and mPAP. The pattern of endothelin-1, prostacyclin, and nitric oxide was distinctive. Levels of endothelin-1 were incrementally increased from mild, moderate, to severe PAH. The levels of prostacyclin and nitric oxide had similar pattern in association with the severity of PAH, which was increased in mild-to-moderate PAH but decreased in severe PAH. CONCLUSIONS: There was a distinctive pattern of endothelin-1, prostacyclin, and nitric oxide based on severity of PAH in adult uncorrected ASD. Significant correlations existed between endothelin-1 and the severity of PAH and mPAP.

The COngenital HeARt Disease in adult and Pulmonary Hypertension (COHARD-PH) registry: a descriptive study from single-center hospital registry of adult congenital heart disease and pulmonary hypertension in Indonesia.

BACKGROUNDS: The COngenital HeARt Disease in adult and Pulmonary Hypertension (COHARD-PH) registry is the first registry for congenital heart disease (CHD) and CHD-related pulmonary hypertension (PH) in adults in Indonesia. The study aims to describe the demographics, clinical presentation, and hemodynamics data of adult CHD and CHD-related PH in Indonesia. METHODS: The COHARD-PH registry is a hospital-based, single-center, and prospective registry which includes adult patients with CHD and CHD-related PH. The patients were enrolled consecutively. For this study, we evaluated the registry patients from July 2012 until July 2019. The enrolled patients underwent clinical examination, electrocardiography, chest x-ray, 6-min walking test, laboratory measurement, and transthoracic and transesophageal echocardiography. Right heart catheterization was performed to measure hemodynamics and confirm the diagnosis of pulmonary artery hypertension (PAH). RESULTS: We registered 1012 patients during the study. The majority were young, adult females. The majority of CHD was secundum ASD (73.4%). The main symptom was dyspnea on effort. The majority of patients (77.1%) had already developed signs of PH assessed by echocardiography. The Eisenmenger syndrome was encountered in 18.7% of the patients. Based on the right heart catheterization, 66.9% of patients had developed PAH. Patients with PAH were significantly older, had lower peripheral oxygen saturation, had lower 6-min walking distance, and higher NTproBNP. The NTproBNP level independently predicted the development of PAH among CHD. CONCLUSIONS: The COHARD-PH registry is the first Indonesian adult-CHD and CHD-related PH registry. The demographics, clinical presentation, and hemodynamics dataof this registry reflect the situation in developing countries which needs to be compared with similar registries from developed countries.

Exercise Program Improves Functional Capacity and Quality of Life in Uncorrected Atrial Septal Defect-Associated Pulmonary Arterial Hypertension: A Randomized-Control Pilot Study.

OBJECTIVE: To assess the effect of combined hospital and home-based exercise programs on functional capacity and quality of life (QoL) among uncorrected atrial septal defect-associated pulmonary arterial hypertension (ASD-PAH) patients. METHODS: This study was a randomized controlled trial with uncorrected ASD-PAH patients as the subjects. They were allocated randomly into control and exercise groups. Exercise group subjects performed hospital and home-based exercise programs, completing baseline 6-minute walking test (6MWT) and EQ-5D-3L QoL test (Utility Index and EQ-VAS scores), and were followed up for 12 weeks. The primary outcomes were 6MWT distance and EQ-5D-3L score at week 12. The N-terminal pro B-type natriuretic peptide (NT-proBNP) level was also assessed. A repeated-measure ANOVA was performed to detect endpoint differences over time. RESULTS: The exercise group contained 20 subjects and control group contained 19. In total, 19 exercise group subjects and 16 control group subjects completed the protocol. The 6MWT distance, Utility Index score, and EQ-VAS score incrementally improved significantly in the exercise group from baseline until week 12, with mean differences of 76.7 m (p<0.001), 0.137 (p<0.001) and 15.5 (p<0.001), respectively. Compared with the control group, the exercise group had significantly increased 6MWT distance and utility index score at week 12. The EQ-VAS score increased in the exercise group at week 12. The NT-proBNP level decreased at week 12 in the exercise group. CONCLUSION: Combined hospital and home-based exercise program added to PAH-targeted therapy, improving functional capacity and QoL in uncorrected ASD-PAH patients.

Takotsubo syndrome in elderly woman: The diagnosis by transthoracic echocardiography.

Takotsubo syndrome has increasingly been recognized in the differential diagnosis of patients presenting with acute chest pain. Those affected are typically older women suffering after an emotional or physical stress. Normally it is a transient condition but complications including death have been reported. We reported a case of takotsubo syndrome who was initially diagnosed as acute coronary syndrome. The patient presented with typical angina, ST-T segment changes, and elevated high sensitive-troponin I. Coronary angiography showed normal coronary arteries. Transthoracic echocardiography revealed mild left atrial dilatation and left ventricle concentric hypertrophy, reduced left ventricle ejection fraction with circumferential hypokinetic, apical ballooning, systolic anterior motion, left ventricle outflow tract obstruction, and sigmoid septum hypertrophy. One month later, patient recovered and transthoracic echocardiography revealed improved heart anatomy and function. To differentiate takotsubo syndrome with other conditions, especially acute coronary syndrome, is crucial. Their clinical presentations are similar but the managements are different. The transthoracic echocardiography holds an important role in supporting the diagnosis of takotsubo syndrome.

The Accuracy of Combined Electrocardiogram Criteria to Diagnose Right Atrial Enlargement in Adults With Uncorrected Secundum Atrial Septal Defect.

BACKGROUND: Right atrium (RA) enlargement in uncorrected atrial septal defect (ASD) is due to chronic volume overload. Several electrocardiogram (ECG) criteria had been proposed for screening RA enlargement. This study aimed to compare the accuracy of ECG criteria in detecting RA enlargement in adults with uncorrected ASD. METHODS: This was a cross-sectional study involving 120 adults with uncorrected secundum ASD. The subjects underwent ECG examination, transthoracic echocardiography, and right heart catheterization. An RA enlargement was determined with RA volume index by transthoracic echocardiography. Various ECG and combined ECG criteria were evaluated. Statistical analysis was performed to analyze the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: An RA enlargement was detected in 64.2% subjects. The P wave height > 2.5 mm in lead II criterion had the best specificity (100%) and PPV (100%), but low sensitivity (19%) and accuracy (48%). The combined 2 ECG criteria (QRS axis > 90°, R/S ratio > 1 in V1) had 82% sensitivity, 56% specificity, 73% accuracy, 77% PPV, and 63% NPV. The combined 3 ECG criteria (QRS axis > 90°, R/S ratio > 1 in V1, and P wave height > 1.5 mm in V2) had 35% sensitivity, 86% specificity, 53% accuracy, 82% PPV, and 43% NPV. CONCLUSIONS: The combined 2 ECG criteria (QRS axis > 90° and R/S ratio > 1 in V1) had increased sensitivity, better accuracy, and more balance of PPV and NPV as compared with P wave > 2.5 mm in II criterion and combined 3 ECG criteria to diagnose RA enlargement in adults with uncorrected ASD.

Economic evaluation of sildenafil for the treatment of pulmonary arterial hypertension in Indonesia.

BACKGROUND: This study aims to assess the cost-effectiveness and budget impact of adopting sildenafil to the benefits package for the indication of pulmonary arterial hypertension (PAH), compared to beraprost. METHODS: Based on a societal perspective, a model-based economic evaluation was performed using local and international data to quantify the potential costs and health-related outcomes in terms of life years (LYs) and quality-adjusted life years (QALYs). RESULTS: The economic model calculated the incremental cost-effectiveness ratio (ICER) per QALY gained for using sildenafil as first-line therapy compared to beraprost for the patient in functional class (FC) II and III, i.e. USD 3098 and USD 2827, respectively. The results indicated that in spite of sildenafil being more expensive than beraprost, generic sildenafil could potentially be a good value for money since ICER per QALY is below one times gross domestic product (GDP) per capita in Indonesia. Furthermore, budget impact analysis estimated that the incremental budget needed within 5 years for including sildenafil compared to beraprost for PAH patients starting in FC II and FC III was USD 436,775 and USD 3.6 million, respectively. CONCLUSIONS: Compared to beraprost, sildenafil would be preferable for the treatment of PAH patients in FC II and FC III in Indonesia. The additional budget for adopting sildenafil compared to beraprost as the treatment of PAH in the benefits package was estimated at around USD 4.0 million.

Right-sided infective endocarditis in patients with uncorrected ventricular septal defect and patent ductus arteriosus: Two case reports.

Uncorrected left-to-right shunt congenital heart defect is a predisposing factor for infective endocarditis (IE), especially right-sided IE which has different clinical manifestations and complications from left-sided IE. Prompt diagnosis by means of transthoracic echocardiography and timely antibiotics management for IE are encouraged to prevent multiorgan failure and fatal pulmonary embolism.

Large Atrial Septal Defect Closure in a Patient with Severe Pulmonary Arterial Hypertension.

Patients with an atrial septal defect (ASD) and severe pulmonary arterial hypertension (PAH) are considered ineligible for defect closure surgery because of the risk of right ventricular decompensation and death after the operation. We report the case of a patient with large ASD and severe PAH who was able to undergo defect closure surgery successfully following long-term use of combined oral sildenafil and beraprost.