Outcomes of patients with COVID-19 and coronary artery disease and heart failure: findings from the Philippine CORONA study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) and coronary artery disease (CAD) or heart failure (HF) are more likely to have poor outcomes. This study aimed to determine the characteristics and outcomes of COVID-19 patients with CAD/HF across various institutions in the Philippines. METHODS: We utilized the data from the Philippine CORONA Study and compared the outcomes of admitted COVID-19 patients with CAD/HF versus those without. The Student's t test, Mann-Whitney U test, binary logistic regression and multivariate regression analysis were utilized. Odds ratios (OR) and Kaplan-Meier curves were generated. RESULTS: We included a total of 512 patients with COVID-19 had CAD/HF and 10,369 were without. CAD/HF was significantly associated with COVID severity, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization. After adjusting for confounders, the presence of CAD/HF was still associated with death from a cardiac cause (OR 2.22, 95% CI 1.49-3.3, p < 0.01). CONCLUSIONS: The presence of CAD or HF was significantly associated with severity of COVID disease, all-cause mortality, death from cardiac causes, respiratory failure, and prolonged hospitalization.

The safety and efficacy of direct oral anticoagulants among chronic kidney disease patients on dialysis with non-valvular atrial fibrillation: a meta-analysis.

Background: Individuals with chronic kidney disease (CKD) on dialysis are at an increased risk of stroke and embolic events especially in the presence of atrial fibrillation (AF). Vitamin K antagonists (VKA), including warfarin, have been used for decades for anticoagulation among CKD patients on dialysis with AF but recent evidence has shown increased bleeding. Direct oral anticoagulants (DOAC) have been emerging as an alternative to VKA which, based on several observational cohort studies, are at least as efficacious and safe as VKA. This meta-analysis looked into the safety and efficacy of DOACs compared to VKA among CKD patients on dialysis with non-valvular AF. Methodology: This study used a random-effects meta-analysis using RevMan 5.4. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were searched from their dates of inception to June 2023. The risk of bias was assessed using Cochrane RoB2 and the certainty of evidence was assessed using GRADE. Results: This meta-analysis showed that DOACs when compared to VKA have no significant difference in terms of risk for major bleeding (RR = 0.81, 95% CI 0.46-1.43), ischemic stroke (RR = 0.5, 95% CI 0.19-1.35), and cardiovascular death (RR = 1.34, 95% CI 0.69-2.60). Discussion: This meta-analysis adds to the growing body of evidence supporting that the use of DOACs has similar efficacy and safety outcomes in CKD patients on dialysis with non-valvular AF patients compared to VKA. The findings need to be replicated in larger and more adequately powered clinical trials in order to ascertain its level of evidence.

Utility of laboratory and immune biomarkers in predicting disease progression and mortality among patients with moderate to severe COVID-19 disease at a Philippine tertiary hospital.

Purpose: This study was performed to determine the clinical biomarkers and cytokines that may be associated with disease progression and in-hospital mortality in a cohort of hospitalized patients with RT-PCR confirmed moderate to severe COVID-19 infection from October 2020 to September 2021, during the first wave of COVID-19 pandemic before the advent of vaccination. Patients and methods: Clinical profile was obtained from the medical records. Laboratory parameters (complete blood count [CBC], albumin, LDH, CRP, ferritin, D-dimer, and procalcitonin) and serum concentrations of cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IFN-γ, IP-10, TNF-α) were measured on Days 0-3, 4-10, 11-14 and beyond Day 14 from the onset of illness. Regression analysis was done to determine the association of the clinical laboratory biomarkers and cytokines with the primary outcomes of disease progression and mortality. ROC curves were generated to determine the predictive performance of the cytokines. Results: We included 400 hospitalized patients with COVID-19 infection, 69% had severe to critical COVID-19 on admission. Disease progression occurred in 139 (35%) patients, while 18% of the total cohort died (73 out of 400). High D-dimer >1 µg/mL (RR 3.5 95%CI 1.83-6.69), elevated LDH >359.5 U/L (RR 1.85 95%CI 1.05-3.25), lymphopenia (RR 1.91 95%CI 1.14-3.19), and hypoalbuminemia (RR 2.67, 95%CI 1.05-6.78) were significantly associated with disease progression. High D-dimer (RR 3.95, 95%CI 1.62-9.61) and high LDH (RR 5.43, 95%CI 2.39-12.37) were also significantly associated with increased risk of in-hospital mortality. Nonsurvivors had significantly higher IP-10 levels at 0 to 3, 4 to 10, and 11 to 14 days from illness onset (p<0.01), IL-6 levels at 0 to 3 days of illness (p=0.03) and IL-18 levels at days 11-14 of illness (p<0.001) compared to survivors. IP-10 had the best predictive performance for disease progression at days 0-3 (AUC 0.81, 95%CI: 0.68-0.95), followed by IL-6 at 11-14 days of illness (AUC 0.67, 95%CI: 0.61-0.73). IP-10 predicted mortality at 11-14 days of illness (AUC 0.77, 95%CI: 0.70-0.84), and IL-6 beyond 14 days of illness (AUC 0.75, 95%CI: 0.68-0.82). Conclusion: Elevated D-dimer, elevated LDH, lymphopenia and hypoalbuminemia are prognostic markers of disease progression. High IP-10 and IL-6 within the 14 days of illness herald disease progression. Additionally, elevated D-dimer and LDH, high IP-10, IL-6 and IL-18 were also associated with mortality. Timely utilization of these biomarkers can guide clinical monitoring and management decisions for COVID-19 patients in the Philippines.

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.

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.

Prognostic impact of coronary collaterals in acute coronary syndrome (PICC-ACS): A meta-analysis of observational studies

INTRODUCTION: The coronary collateral circulation (CCC) is an alternative source of blood supply in coronary artery disease (CAD). The prognostic value of the presence of CCC at the time of acute coronary syndrome (ACS) is undefined with regards to hard outcomes, particularly reduction in mortality. The study's aim is to determine if the presence of CCC demonstrated by coronary angiography during an ACS is associated with a reduction in mortality.  METHODS: We conducted a systematic search of studies using MEDLINE, EMBASE, ScienceDirect, Scopus, and Cochrane Central Register of Controlled Trials databases in all languages and examined reference lists of studies. The inclusion criteria were 1) observational; 2) population included adults >19 years old with an acute coronary syndrome; 3) reported data on mortality in association with the presence or absence of CCC on angiography; and 4) should have controlled for confounders by using logistic regression analysis. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale for observational studies. The outcome of interest was reduction in all-cause mortality, assessed using Mantel-Haenzel analysis of random effects to compute for risk ratios. RESULTS: Pooled analysis from 11 identified trials with 8,370 subjects showed that among patients with ACS who underwent coronary angiography, the presence of CCC showed a trend towards benefit in terms of mortality, but was not statistically different from those without CCC [RR 0.65, (95% CI 0.38 to 1.12), p CONCLUSION: The presence of CCC during ACS showed a trend towards mortality reduction. Further, among patients treated with PCI, those with CCC had an incrementally significant reduction in mortality compared to those without CCC.

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.

Cardiac tamponade as a rare manifestation of systemic lupus erythematosus: A report on four cases in the Philippine General Hospital

SYNOPSIS: Cardiac tamponade among systemic lupus erythematosus (SLE) patients is an unusual event. The pericardial effusion may be a consequence of uremia, infections in the pericardium, or the lupus pericarditis itself. We present four atypical cases of cardiac tamponade from pericarditis of connective tissue disease (CTD), all of which were treated with drainage and immunosuppressants. Due to the rarity of this combination, management was a challenge.CLINICAL PRESENTATION: Four females each sought consult for dyspnea associated with typical manifestations of connective tissue disease such as arthritis, characteristic rashes, serositis, typical laboratory features, and a positive ANA and/or anti-dsDNA. The first three cases fulfilled the criteria for SLE, while the fourth fulfilled the criteria for SLE-dermatomyositis overlap syndrome. Echocardiography was done due to suspicion of pericardial involvement and revealed massive pericardial effusion in tamponade physiology in all cases.DIAGNOSIS: Cardiac tamponade from serositis due to connective tissue disease [SLE (case 1 to 3) or SLE-dermatomyositis overlap (case 4). Other common etiologies of tamponade such as bacterial, tuberculous, malignant, and uremic pericardial effusion were ruled out by clinical and laboratory tools, including Gram stain and culture, cytology, PCR, and biochemical testing. The pericardial fluid of the first case tested positive for lupus erythematosus (LE) cells, indicative of lupus serositis.TREATMENT AND OUTCOME: All patients underwent pericardial drainage via tube pericardiostomy. They received high dose glucocorticoids after infectious etiologies for the pericardial effusion were ruled out. The fourth case with the overlap syndrome, however, required more immunosuppressants using azathioprine and methotrexate. Resolution of pericardial effusion was noted with this approach. Three of four were discharged improved, however, the third case suffered from worsening nephritis and pulmonary hemorrhage leading to her demise.SIGNIFICANCE AND RECOMMENDATIONS: Four cases of cardiac tamponade as a manifestation of connective tissue disease were presented. Literature underlines the rarity of this condition anytime during the course of SLE. Despite this, SLE should be considered as one of the differential diagnosis of cardiac tamponade, especially in patients who manifest with multi-systemic findings. Likewise, massive pericardial effusion should be considered in patients with a connective tissue disease presenting with subtle evidence of pericardial involvement. It requires timely identification and treatment with high dose steroids, after other causes such as infections have been excluded. Immediate drainage through pericardiocentesis or pericardiostomy in combination with immunosuppressants may be life-saving.

Clinical and echocardiographic profile and outcomes of peripartum cardiomyopathy: the Philippine General Hospital experience.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare disease entity of unknown aetiology. High rates of mortality or poor overall clinical outcome are reported in women with this condition. Certain characteristics are risk factors for this disease. In Asia, there are limited data, especially in the Southeast Asian region. In the Philippines, no data exist regarding the prevalence or risk factors. OBJECTIVES: To determine the prevalence, profile and outcomes of PPCM in Philippine General Hospital and to describe their echocardiographic findings. METHODS: All patients diagnosed with PPCM in the period of 1 January 2009-31 December 2010 were seen and examined. Demographic data and echocardiogram of the patients were reviewed. RESULTS: 9 were diagnosed with PPCM during the study period. The prevalence is 1 in 1270 live births. Mean age was 29. 78% presented with moderate to severe heart failure symptoms in the prepartum period. Among purported risk factors for PPCM, obesity, multiparity and pre-eclampsia were seen in most. Conversely, only one patient admitted to having more than a single sexual partner. Only one patient had multifetal pregnancy. None were smokers. 44% underwent caesarean section for maternal indication. No mortality was seen. Fetal outcomes were good with all resulting in live births and most were appropriate for gestational age. Echocardiographic findings showed global wall motion abnormalities in the majority, mean ejection fraction of 34% and mean fractional shortening of 20%. CONCLUSIONS: PPCM is rare in the Philippines. Compared with international data, our patients are younger with low percentages of promiscuity, multifetal pregnancy, smoking history and tocolytic use. Similar to previous studies, obesity, multiparity and pre-eclampsia were also present in our PPCM patients. Immediate maternal and fetal outcomes were generally good. Adherence to standard heart failure management is high.