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.

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.

Ivabradine Versus Beta-Blockers in Mitral Stenosis in Sinus Rhythm: An Updated Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Symptoms of mitral stenosis (MS) are worsened during tachycardia and exercise. Beta-blockers are used in controlling heart rate (HR) in MS, resulting in symptom improvement, but coming with significant side effects. Ivabradine has a selective action on the sinus node devoid of the usual side effects of beta-blockers. Small studies have recently investigated the role of ivabradine in MS in sinus rhythm. Our aim was to determine the efficacy of ivabradine, compared to beta-blockers, in terms of exercise duration, maximum HR achieved, resting HR, mean gradient, and working capacity among patients with MS in sinus rhythm. METHODS: We conducted a systematic search of studies using MEDLINE, Google Scholar, ScienceDirect, Scopus, Clinical Key, Cochrane, and clinicaltrials.gov databases in all languages and examined reference lists of studies. We included studies if they are: 1) randomized controlled trials comparing ivabradine and beta-blockers; 2) of adults ≥ 19 years old with MS in sinus rhythm; and 3) reported data on exercise duration, maximum HR achieved, resting HR, mean gradient, and working capacity. Studies identified were assessed for risk of bias using the Cochrane Collaboration Tool for Assessing Risk of Bias. We used inverse variance analysis of fixed effects to compute for mean difference, carried out using Review Manager (RevMan) 5.3. RESULTS: Pooled analysis from five identified trials showed that among patients with MS in sinus rhythm, ivabradine was better compared to beta-blockers in total exercise duration (mean difference: 32.73 s (95% CI: 12.19, 53.27; P = 0.002; I2 = 0%)), maximum HR achieved after exercise (mean difference: -3.87 beats per minute (95% CI: -5.88, -1.860; P = 0.0002; I2 = 23%)), and work capacity (mean difference: 0.56 METS (95% CI: 0.33, 0.80; P < 0.00001; I2 = 0%)); inferior to beta-blockers in resting HR achieved (mean difference: 1.83 s (95% CI: 0.39, 3.28; P = 0.01; I2 = 91%)); and comparable to beta-blockers in terms of mean gradient (mean difference: -0.52 mm Hg (95% CI: -1.20, 0.16; P = 0.13; I2 = 6%)). CONCLUSIONS: Ivabradine is better or comparable to beta-blockers in terms of the outcomes measured, and may be considered as an alternative for patients with MS in sinus rhythm who are intolerant to beta-blockers.

Red Cell Distribution Width and Mortality in Patients With Acute Coronary Syndrome: A Meta-Analysis on Prognosis.

BACKGROUND: Red cell distribution width (RDW), a routine component of the complete blood count (CBC), measures variation in the size of circulating erythrocytes. It has been associated with several clinical outcomes in cardiovascular disease. We sought to strengthen the association between RDW and mortality in patients admitted for acute coronary syndrome (ACS) by pooling together data from available studies. METHODS: Studies that fulfilled the following were identified for analysis: 1) observational; 2) included patients admitted for ACS; 3) reported data on all-cause or cardiovascular (CV) mortality in association with a low or high RDW; and 4) used logistic regression analysis to control for confounders. Using MEDLINE, Clinical Key, ScienceDirect, Scopus, and Cochrane Central Register of Controlled Trials databases, a search for eligible studies was conducted until January 9, 2017. The quality of each study was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Our primary outcome of interest was all-cause or CV mortality. We also investigated the impact of RDW on major adverse cardiovascular events (MACEs) for the studies that reported these outcomes. Review Manager (RevMan) 5.3 was utilized to perform Mantel-Haenzel analysis of random effects and compute for relative risk. RESULTS: We identified 13 trials involving 10,410 patients, showing that in ACS, a low RDW is associated with a statistically significant lower all-cause or CV mortality (RR 0.35, (95% CI 0.30 to 0.40), P < 0.00001, I2 = 53%), a finding that was consistent both in the short- and long-term. CONCLUSIONS: A low RDW is also associated with lower risk for MACEs after an ACS (RR 0.56, (95% CI 0.51 to 0.61), P < 0.00001, I2 = 91%). A low RDW during an ACS is associated with lower all-cause or CV mortality and lower risk of subsequent MACEs, providing us with a convenient and inexpensive risk stratification tool in ACS patients.

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.

Targeted next generation sequencing of the entire vitamin D receptor gene reveals polymorphisms correlated with vitamin D deficiency among older Filipino women with and without fragility fracture.

This study aimed to discover genetic variants in the entire 101 kB vitamin D receptor (VDR) gene for vitamin D deficiency in a group of postmenopausal Filipino women using targeted next generation sequencing (TNGS) approach in a case-control study design. A total of 50 women with and without osteoporotic fracture seen at the Philippine Orthopedic Center were included. Blood samples were collected for determination of serum vitamin D, calcium, phosphorus, glucose, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase and as primary source for targeted VDR gene sequencing using the Ion Torrent Personal Genome Machine. The variant calling was based on the GATK best practice workflow and annotated using Annovar tool. A total of 1496 unique variants in the whole 101-kb VDR gene were identified. Novel sequence variations not registered in the dbSNP database were found among cases and controls at a rate of 23.1% and 16.6% of total discovered variants, respectively. One disease-associated enhancer showed statistically significant association to low serum 25-hydroxy vitamin D levels (Pearson chi-square P-value=0.009). The transcription factor binding site prediction program PROMO predicted the disruption of three transcription factor binding sites in this enhancer region. These findings show the power of TNGS in identifying sequence variations in a very large gene and the surprising results obtained in this study greatly expand the catalog of known VDR sequence variants that may represent an important clue in the emergence of vitamin D deficiency. Such information will also provide the additional guidance necessary toward a personalized nutritional advice to reach sufficient vitamin D status.

The role of prophylactic renin-angiotensin system inhibitors for the prevention of anthracycline-induced cardiotoxicity among adult cancer patients: A meta-analysis

INTRODUCTION: Anthracycline is a cornerstone in the treatment of various cancers. One major limitation to its use is cardiotoxicity. Renin angiotensin system (RAS) inhibitors have been shown to attenuate myocardial injury, initial data is promising in its use as prophylaxis for anthracyclineinduced cardiotoxicity. The aim of the study is to determine effectiveness of prophylactic RAS inhibitors in preventing anthracycline-induced cardiotoxicity and adverse cardiac events among adult cancer patients METHODS: Systematic search of databases PUBMED, MEDLINE, EMBASE, and CENTRAL was done. Selection criteria were: 1) randomized controlled trials (RCT) 2) adult cancer patients with normal ejection fraction and without heart failure symptoms 3) RAS inhibitors as prophylaxis versus placebo 4) development of cardiac events, all-cause mortality and left ventricular ejection fraction (LVEF) reduction as outcomes. Two reviewers independently assessed the trials. Disagreements were resolved with a third reviewer. Test for effect of intervention, heterogeneity, trial quality and risk of bias were assessed using the Cochrane Review Manager Software version 5.3. RESULTS: Five RCTs involving 530 adult patients, with average age of 50± two years old, and average follow-up from six months to three years were included. Combined clinical outcomes of heart failure, cardiac events and all-cause mortality showed an RR of 0.27[95%CI 0.18, 0.40],p CONCLUSION: Renin angiotensin system (RAS) inhibitors may be used as prophylaxis for cardiotoxicity. As prophylaxis, it reduced the clinical outcome of cardiac events, heart failure, and all-cause mortality among cancer patients needing anthracycline. Combined RAS inhibitor and betablocker limits LVEF reduction.

Association of the platelet-lymphocyte ratio (PLR) with outcomes in patients admitted for acute coronary syndrome: The PLACS study

INTRODUCTION: Patients with acute coronary syndrome (ACS) exhibit a wide spectrum of early risk of death (one to 10 percent). High platelet counts may indicate a propensity for platelet-rich thrombi. Lymphocyte counts drop during ACS due to stress-induced cortisol release. Combining these two markers, recent studies have found that the platelet-tolymphocyte ratio (PLR) is associated with adverse cardiac events among patients with ACS, but local data is limited. The objective of this study is to determine if an elevated PLR taken on admission is associated with higher rates of adverse cardiac events. METHODS: A retrospective cohort of adult patients with ACS admitted at the UP-Philippine General Hospital was analyzed. Leukocyte and platelet counts were measured by an automated hematology analyzer. The PLR values of these patients were computed, and they were stratified into two groups after determining the optimal cut-off from the receiver operating characteristic curve (ROC) curve. The primary outcome was in-hospital mortality. Secondary outcomes included development of heart failure, cardiogenic shock, reinfarction, and significant arrhythmias. RESULTS: A total of 174 Filipinos with ACS were included. In-hospital mortality occurred in 30 patients (17%). These patients had a higher PLR compared to those who were discharged alive (p-value CONCLUSION: Among Filipino patients with ACS, an elevated PLR taken within 24 hours of admission is a useful marker to predict in-hospital mortality, thus providing vital information for risk stratification and more aggressive management strategies.

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.

A Filipino with polyangiitis overlap syndrome and associated multiple infections

BACKGROUND: Polyangiitis overlap syndrome (POS),a systemic vasculitis not classifiable into well-defined syndromes, is  diagnosed based on combined characteristics of two or more primary systemic vasculitides, such as Takayasu arteritis  and anti-neutrophil cytoplasmic antibody (ANCA)-associated  vasculitis  (AAV), but not two AAVs. Our objective is to   present such,   with associated  multiple  infections.CASE: A  25-year-old  Filipino  female  had  six  years  of  recurrent  purpura,  debilitating  joint  pains,  hemoptysis,  rhinorrhea, epistaxis, eye redness, dyspnea,  and  abdominal  cramps. She was cachectic, had oral ulcers, bibasal  crackles,  polyarthritis,  and  generalized  purpura.   Work-up   showed   anemia,   eosinophilia  excluding   parasitism,   elevated inflammatory markers, and  positive cytoplasmic (c)-ANCA and anti-proteinase 3. There   was   chronic sinusitis on rigid rhinoscopy, middle to lower lung field  interstitial   infiltrates   on   radiographs, pulmonary vasculitis   on  chest   CT,   moderate pulmonary hypertension on  echocardiography,  but  normal  spirometry.  Skin  biopsy  showed  leukocytoclastic vasculitis without  necrotizing  granulomas.Serology showed chronic hepatitis B infection.   Pseudomonas  aeruginosa and  methicillin-resistant Staphylococcus  aureus  grew  from  bronchial  washings and   nasal   swabs,   respectively. ASO titer was high. Human  immunodeficiency  virus  infection  was  ruled  out.  She   was   diagnosed with POS,with features of two AAVs- limited granulomatosis   with   polyangiitis   (GPA)   and   Churg-Strauss   syndrome  (CSS), associated with   multiple  infections,   and  was  given naproxen and culture-guided   antibiotics  (ciprofloxacin, clindamycin, penicillin),with partial resolution of symptoms.  Prednisone   10  mg once  a  day (OD)  was   started  two weeks   after hepatitis B reactivation prophylaxis   with   lamivudine 100mg OD. Complete   resolution of skin lesions and upper airway symptoms and    inflammatory  marker  improvement  were observed after 12  weeks. She is  maintained on prednisone   5.0   mg   daily.CONCLUSION AND RECOMMENDATIONS: This   is   the   first   reported   case   of   POS   involving   two   AAVs   -   limited   GPA   and   incomplete   CSS,   associated   with   multiple   pathogens.Identifying  POS  is  important;    inability to  classify patients  into well-recognized  vasculitic  syndromes  delays  treatment.  The  infections likely  perpetuated   the   vasculitis,  and  both antimicrobials  and  immunosuppression were  necessary  to  induce   disease   remission