Management of Hypertension in the Asia-Pacific Region: A Structured Review.

This article reviews available evidence regarding hypertension management in the Asia-Pacific region, focussing on five research questions that deal with specific aspects: blood pressure (BP) control, guideline recommendations, role of renin-angiotensin-aldosterone system (RAAS) inhibitors in clinical practice, pharmacological management and real-world adherence to guideline recommendations. A PubMed search identified 2537 articles, of which 94 were considered relevant. Compared with Europeans, Asians have higher systolic/diastolic/mean arterial BP, with a stronger association between BP and stroke. Calcium channel blockers are the most-commonly prescribed monotherapy in Asia, with significant variability between countries in the rates of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin-receptor blockers (ARBs) and single-pill combination (SPC) use. In clinical practice, ARBs are used more commonly than ACEis, despite the absence of recommendation from guidelines and clinical evidence supporting the use of one class of drug over the other. Ideally, antihypertensive treatment should be tailored to the individual patient, but currently there are limited data on the characteristics of hypertension in Asia-Pacific individuals. Large outcome studies assessing RAAS inhibitor efficacy and safety in multi-national Asian populations are lacking. Among treated patients, BP control rates were ~ 35 to 40%; BP control in Asia-Pacific is suboptimal, and disproportionately so compared with Western nations. Strategies to improve the management of hypertension include wider access/availability of affordable treatments, particularly SPCs (which improve adherence), effective public health screening programs targeting patients to drive health-seeking behaviours, an increase in physician/patient awareness and early implementation of lifestyle changes. A unified Asia-Pacific guideline on hypertension management with pragmatic recommendations, particularly in resource-limited settings, is essential.

The rs1458038 variant near FGF5 is associated with poor response to calcium channel blockers among Filipinos.

ABSTRACT: Genetic variation is known to affect response to calcium channel blockers (CCBs) among different populations. This study aimed to determine the genetic variations associated with poor response to this class of antihypertensive drugs among Filipinos.One hundred eighty one hypertensive participants on CCBs therapy were included in an unmatched case-control study. Genomic deoxyribonucleic acid were extracted and genotyped for selected genetic variants. Regression analysis was used to determine the association of genetic and clinical variables with poor response to medication.The variant rs1458038 near fibroblast growth factor 5 gene showed significant association with poor blood pressure-lowering response based on additive effect (CT genotype: adjusted OR 3.41, P = .001; TT genotype: adjusted OR 6.72, P < .001).These findings suggest that blood pressure response to calcium channels blockers among Filipinos with hypertension is associated with gene variant rs1458038 near fibroblast growth factor 5 gene. Further studies are recommended to validate such relationship of the variant to the CCB response.

Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients: A Five-Year Retrospective Study in 10 Centers.

Background: Cardiotoxicity as a result of anthracycline chemotherapy has been linked to increased morbidity and mortality in breast cancer patients. There is a need for early detection through risk factor identification. To date, no large multicenter study has been conducted to describe the incidence, risk factors and clinical and demographic profiles of breast cancer patients with anthracycline-induced cardiotoxicity (AIC) in the Philippines. Methods: This was a nationwide multicenter retrospective cohort study among adult breast cancer patients who underwent anthracycline chemotherapy from 2015 to 2020 in 10 sites in the Philippines. Baseline characteristics and possible risk factors for AIC were retrieved from medical records and cancer registries. AIC was defined as a reduction of left ventricular ejection fraction (LVEF) by > 10% from baseline to a value of < 53% or the development of overt left ventricular systolic dysfunction or heart failure (HF). Odds ratios from logistic regression were computed to determine risk factors associated with AIC using STATA-15.0 software. Results: Out of 341 patients included, 33 had AIC, accounting for an incidence of 9.68%. Nine patients (2.6%) had clinical HF. AIC patients had a mean age of 53.91 ± 10.84 years. Breast cancer AIC patients were significantly older and had lower body mass index (BMI) than those without AIC. AIC patients had significantly more comorbidities, especially hypertension and atrial fibrillation. Multivariate analysis showed that patients with any preexisting comorbidity are approximately 12.37 times as likely to have AIC, while those with concurrent chemotherapy are 0.07 times or 93% less likely to have AIC. Conclusion: Among adult breast cancer patients undergoing anthracycline chemotherapy, we determined a high incidence of cardiotoxicity at 9.68%. Having preexisting comorbidities gave patients 12 times increased odds of developing anthracycline cardiotoxicity. The presence of concurrent non-anthracycline chemotherapy showed an inverse association with the development of AIC which we attribute largely to patient selection in a retrospective study. The significantly higher propensity for AIC development in patients with preexisting comorbidities may warrant closer monitoring and control of patient comorbidities such as hypertension among patients undergoing anthracycline chemotherapy.

The Klotho Variant rs36217263 Is Associated With Poor Response to Cardioselective Beta-Blocker Therapy Among Filipinos.

A common drug used for hypertension among Filipinos is beta-blockers. Variable responses to beta-blockers are observed, and genetic predisposition is suggested. This study investigated the association of genetic variants with poor response to beta-blockers among Filipinos. A total of 76 Filipino adult hypertensive participants on beta-blockers were enrolled in an unmatched case-control study. Genotyping was done using DNA from blood samples. Candidate variants were correlated with clinical data using χ2 and logistic regression analysis. The deletion of at least one copy of allele A of rs36217263 near Klotho showed statistically significant association with poor response to beta-blockers (dominant; odds ratio (OR) = 3.89; P = 0.017), adjusted for diabetes and dyslipidemia. This association is observed among participants using cardioselective beta-blockers (crude OR = 5.60; P = 0.008) but not carvedilol (crude OR = 2.56; P = 0.67). The genetic variant rs36217263 is associated with poor response to cardioselective beta-blockers, which may become a potential marker to aid in the management of hypertension.

Pulmonary Artery and Pulmonic Valve Vegetations in a Young Pregnant Filipino with Patent Ductus Arteriosus.

BACKGROUND: Infective endocarditis (IE) involving the pulmonic valve and/or the pulmonary artery is rare. An unrepaired patent ductus arteriosus (PDA) is a risk factor for IE. A previous IE is also a risk factor that predisposes to IE recurrence. Discriminating between IE recurrence and a persistence of a vegetation from a previously treated IE can be difficult. We present the case of a 19-year-old primigravid with an unrepaired PDA and a history of IE treated 7 years prior, with positive blood cultures and vegetations on the pulmonic valve and pulmonary artery seen on transthoracic echocardiogram (TTE). METHODS AND RESULTS: On TTE, a small-sized PDA with a Qp : Qs of 1.18 and vegetations on the pulmonic valve and pulmonary artery were documented. Despite the paucity of symptoms, she was empirically treated as culture-negative IE and given 2 weeks of ceftriaxone. Repeat TTE done after 2 weeks only showed a slight decrease in the vegetation size. Due to the paucity of symptoms of infection, lack of growth of the vegetation, and absence of embolic events, the vegetations were deemed to be persistent remnants from the previous IE rather than a recurrent IE. She was advised surgical PDA closure and harvest of vegetations after delivery, but the patient did not consent. The rest of her perinatal course was uneventful. CONCLUSION: Persistence of vegetations despite successful medical treatment occurs in some cases and has not been reported to be associated with increased morbidity. Therefore, a follow-up of IE after treatment should be guided by the clinical course and response to therapy as well as the echocardiographic morphology of vegetations over time.

Systolic Anterior Motion of Mitral Valve Subchordal Apparatus: A Rare Echocardiographic Pattern in Non-Obstructive Hypertrophic Cardiomyopathy.

Systolic anterior motion (SAM) of the mitral valve or chordate is one characteristic seen in hypertrophic cardiomyopathy (HCM) either in obstructive or non-obstructive phenotypes. More often than not, the obstruction is caused by valvular rather than chordal SAM. We describe the role of echocardiography in identifying the actual anatomical location of the mitral valve apparatus involved in SAM and in assessing consequent left ventricular outflow tract (LVOT) obstruction in an otherwise asymptomatic patient. We report a case of a 29-year-old male admitted for an elective non-cardiac surgery, presenting with a cardiac murmur and left axis deviation with biventricular hypertrophy on electrocardiogram. On 2D transthoracic echocardiography (TTE), an asymmetrically hypertrophied left ventricle with systolic motion of anterior mitral valve was incidentally seen. Continuous wave Doppler assessment across the LVOT showed some gradient of obstruction (peak gradient: 9 mm Hg). Transesophageal echocardiography (TEE) demonstrated a redundant anterior mitral valve with the subchordal apparatus mainly causing SAM and confirmed the gradient obtained on TTE, with a mild degree, yet non-significant, degree of LVOT obstruction (mean gradient: 10 mm Hg) documented. Because of this finding, patient was cleared for surgery. Management was deemed conservative with emphasis on close surveillance for signs and symptoms attributable to development of significant LVOT obstruction in patients with HCM. To our knowledge, this is the first reported case in our country of an echocardiographic pattern of systolic anterior motion primarily of the subchordal mitral valve apparatus causing some, though non-significant, degree of LVOT obstruction in HCM. Echocardiographic features such as asymmetric left ventricular hypertrophy and presence of some LVOT obstruction caused primarily by subchordal apparatus could impact management in asymptomatic patients.

A Rare Case of Pneumopericardium in the Setting of Tuberculous Constrictive Pericarditis.

A 28-year-old Filipino male was admitted due to high-grade fevers and dyspnea on a background of chronic cough and weight loss. Due to clinical and echocardiographic signs of cardiac tamponade, emergency pericardiocentesis was performed on his first hospital day. Five days after, chest radiographs showed new pockets of radiolucency within the cardiac shadow, indicative of pneumopericardium. On repeat echo, air microbubbles admixed with loculated effusion were visualized in the anterior pericardial space. Constrictive physiology was also supported by a thickened pericardium, septal bounce, exaggerated respiratory variation in AV valve inflow, and IVC plethora. A chest CT scan confirmed the presence of an air-fluid level within the pericardial sac. The patient was started on a quadruple antituberculosis regimen and IV piperacillin-tazobactam to cover for superimposed acute bacterial pericarditis. Pericardiectomy was performed as definitive management, with stripped pericardium measuring 5-7 mm thick and caseous material extracted from the pericardial sac. Histopathology was consistent with tuberculosis. This report highlights pneumopericardium as a rare complication of pericardiocentesis. We focused on the utility of echocardiography for diagnosing and monitoring this condition on a background of tuberculous constrictive pericarditis, ultimately convincing us that pericardiectomy was necessary, instead of the usual conservative measures for pneumopericardium.

Pulmonary vein mass with extension to the left atrium diagnosed by echocardiography.

We report a case of a man aged 65 years presenting with chronic cough, haemoptysis and intermittent atrial tachyarrhythmias on ECG. On 2D transthoracic echocardiography, an incidental left atrial mass was seen, initially thought to be a thrombus predisposed by intermittent atrial fibrillation. Transoesophageal echocardiography confirmed that this left atrial mass originated from a fixed, non-homogenous, right superior pulmonary vein mass with an extracardiac extension. Because of this finding, a thorough search for a primary focus lead to the discovery of a contiguous posterior mediastinal mass, which was a round cell neoplasm on histology. Management was deemed palliative. Although rare, left-sided cardiac masses should prompt the physician to search for a malignancy in the lung in high-risk patients, as haematogenous spread via the pulmonary vein is a potential mechanism for spread.

Prediction of Symptomatic Embolism in Filipinos With Infective Endocarditis Using the Embolic Risk French Calculator.

BACKGROUND: Cardioembolic events are life-threatening complications of infective endocarditis (IE). The embolic risk French calculator estimates the embolic risk in IE computed on admission. Variables in this tool include age, diabetes, atrial fibrillation, prior embolism, vegetation length, and Staphylococcus aureus on culture. A computed risk of > 7% was considered high in the development of this tool. Knowledge of this risk applied in our local setting is important to guide clinicians in preventing such catastrophic complications. Among patients with IE, we aim to determine the efficacy of the embolic risk French calculator, using a computed score of > 7%, in predicting major embolic events. METHODS: All adults admitted from 2013 to 2016 with definite IE were included. The risk for embolic events was computed on admission. All were monitored for the duration of admission for the occurrence of the primary outcome (any major embolic event: arterial emboli, intracranial hemorrhage, pulmonary infarcts, or aneurysms). Secondary outcomes were: 1) composite of death and embolic events; and 2) death from any cause. RESULTS: Eighty-seven adults with definite IE were included. Majority had a valvular heart disease and preserved ejection fraction (EF). The mitral valve was most commonly involved. Embolic events occurred in 25 (29%). Multivariate analysis identified a high embolic score > 7% (relative risk (RR): 15.12, P < 0.001), vegetation area ≥ 18 mm2 (RR: 6.39, P < 0.01), and a prior embolism (RR: 5.18, P = 0.018) to be independent predictors of embolic events. For the composite of embolic events and death, independent predictors include a high score of > 7% (RR: 13.56, P < 0.001) and a prior embolus (RR: 13.75, P = 0.002). Independent predictors of death were a high score > 7% (RR: 6.20, P = 0.003) and EF ≤ 45% (RR: 9.91, P = 0.004). CONCLUSION: Cardioembolic events are more prevalent in our study compared to previous data. The embolic risk French calculator is a useful tool to estimate and predict risk for embolic events and in-hospital mortality. The risk of developing embolic events should be weighed against the risks of early preventive cardiac surgery, as to institute timely and appropriate management.

A rare case of an intracardiac hemangioma causing significant right ventricular outflow tract obstruction

INTRODUCTION: Cardiac hemangiomas are rare benign primary tumors.We present the successful management of a patient with a hemangioma causing significant right ventricular outflow tract (RVOT) obstruction.CLINICAL PRESENTATION: A 54-year-old  female  with  no  co-morbidities  presented  with  progressive  right-sided  heart failure  symptoms.Examination  revealed  a  prominent right  ventricular  heave,  irregular  cardiac  rhythm,murmurs  consistent  with  pulmonic  stenosis  and  tricuspid regurgitation,  ascites,  and  bipedal  edema.  Given the echo features of the mass and the patient's clinical course,we  favored  a  benign  cardiac  tumor  over  malignancy.Differentials included  myxoma,  fibroma,  and  papillary fibroelastoma. Medical management included enoxaparin and carvedilol as anticoagulation and rate control for the atrial flutter, respectively. Surgical treatment consisted of tumor excision and tricuspid valve annuloplasty.RESULTS: Intra-operatively, the stalk was indeed attached to the RV free wall. Histopathology was consistent with primary cardiac hemangioma. The patient's post-operative course was complicated by pneumonia, acute kidney injury, and tracheostomy, but she was eventually discharged improved after a month in the ICU.SIGNIFICANCE: This report highlights a rare primary cardiac tumor in an unusual location. While there have been several reports in the world literature on cardiac hemangiomas, less than ten cases have been shown to have significant RVOT obstruction as in our patient.CONCLUSION: Cardiac hemangiomas should be part of the differential diagnosis for an intracardiac mass in the right ventricle.  Meticulous  echocardiography  can  be  a  non-invasive and inexpensive aid to diagnosis and pre-operative planning.

Coarctation of the Aorta and a Parachute Mitral Valve in an Adult With Differential Cyanosis.

Differential cyanosis may occur in Eisenmenger physiology in the presence of a patent ductus arteriosus (PDA). We present a unique case of a 22-year-old male manifesting as cyanosis of the left upper extremity and both lower extremities, but with preservation of the right upper extremity. Work-up revealed multiple congenital defects, reminiscent of the Shone's complex. Survival into adulthood is presumed to be due to a PDA, at the expense of a right-to-left shunt. This report highlights the interplay of multiple anomalies documented on echocardiography and MRI, wherein diagnosis was made non-invasively.

The Triply Twisted Heart: Cyanosis in an Adult With Situs Inversus, Levocardia, Double Outlet Right Ventricle, and Malposition of the Great Arteries.

We present a case of a 19-year-old female presenting with cyanosis since birth. The major anomaly demonstrated was a "triply twisted heart" with a balanced physiology, allowing her to survive into adulthood. Non-invasive imaging was done using 2D and real-time 3D (or 4D) echocardiography with multi-slice imaging from 4D volume datasets. Findings were confirmed using cardiac magnetic resonance imaging (MRI). A segmental approach revealed atrial and visceral situs inversus, levocardia, atrioventricular discordance, and ventriculoarterial discordance. Both the aorta and pulmonary artery were malposed and arise from the right ventricle (double outlet right ventricle or DORV). There was also a complete atrioventricular septal defect (CAVSD) associated with a functional single atrium and a functional univentricle (single ventricle). Other findings include a severe pulmonic stenosis (PS), preserved right and left ventricular systolic function, and a normal pulmonary arterial pressure. She also had a persistent left superior vena cava (SVC) that drains into the morphologic right atrium, while the right-sided SVC drains into the morphologic left atrium. A multidisciplinary team deemed that management be palliative. She is on regular follow-up at our clinics for non-invasive monitoring. To our knowledge, this is the first reported case in an adult with this combination of anomalies.

Cushing's syndrome in pregnancy.

A 22-year-old G(1)P(0) was admitted at 26 weeks gestation for preeclampsia, hyperglycaemia and cushingoid features. Elevated 24-h urine free cortisol (UFC) and suppressed plasma adrenocorticotrophic hormone (ACTH) suggested ACTH-independent Cushing's syndrome. Ultrasound showed left adrenal mass. She delivered preterm at 28 weeks due to severe preeclampsia and fetal distress. The infant expired after 4 days. Blood pressure was controlled after delivery and the patient was discharged on ketoconazole. Adrenalectomy was planned postpartum; however, she withdrew consent and was lost to follow-up. A 33-year-old G(1)P(1) presented with gestational diabetes. Pregnancy was complicated by premature delivery at 31 weeks for fetal distress. The baby improved and survived. Three months postpartum, she was evaluated for osteoporosis after sustaining a fracture from a fall. Cushingoid facies, elevated 24-h UFC, suppressed ACTH and a right adrenal mass on MRI confirmed an ACTH-independent Cushing's syndrome. She underwent adrenalectomy and improved.