Characteristics of patients admitted with heart failure: Insights from the first Malaysian Heart Failure Registry.

AIMS: Heart failure (HF) is a growing health problem, yet there are limited data on patients with HF in Malaysia. The Malaysian Heart Failure (MY-HF) Registry aims to gain insights into the epidemiology, aetiology, management, and outcome of Malaysian patients with HF and identify areas for improvement within the national HF services. METHODS AND RESULTS: The MY-HF Registry is a 3-year prospective, observational study comprising 2717 Malaysian patients admitted for acute HF. We report the description of baseline data at admission and outcomes of index hospitalization of these patients. The mean age was 60.2 ± 13.6 years, 66.8% were male, and 34.3% had de novo HF. Collectively, 55.7% of patients presented with New York Heart Association (NYHA) Class III or IV; ischaemic heart disease was the most frequent aetiology (63.2%). Most admissions (87.3%) occurred via the emergency department, with 13.7% of patients requiring intensive care, and of these, 21.8% needed intubation. The proportion of patients receiving guideline-directed medical therapy increased at discharge (84.2% vs. 93.6%). The median length of stay (LOS) was 5 days, and in-hospital mortality was 2.9%. Predictors of LOS and/or in-hospital mortality were age, NYHA class, estimated glomerular filtration rate, and comorbid anaemia. LOS and in-hospital mortality were similar regardless of ejection fraction. CONCLUSIONS: The MY-HF Registry showed that the HF population in Malaysia is younger, predominantly male, and ischaemic-driven and has good prospects with hospitalization for optimization of treatment. These findings suggest a need to reassess current clinical practice and guide resource allocation to improve patient outcomes.

Aortic root pseudoaneurysm: a case report and literature review.

Pseudoaneurysms of the aortic root are rare. A case of prosthetic aortic valve infection progressing from a confined intramural abscess to a ruptured abscess communicating with the aorta and forming a large pseudoaneurysm is described. Additionally, data from all cases and case series, published between 2000 and 2021, was analyzed. A PUBMED search for the keywords "aortic root mycotic aneurysm," "aortic root abscess AND infective endocarditis," and "aortic root mycotic aneurysm AND infective endocarditis" yielded 152 publications (with 157 cases described): Aortic pseudoaneurysm is more common in males (80.9%, n = 127). Mean age is 51 years (4 months-84 years). The most common symptom is fever (68.5%, n = 102). Mean time until diagnosis is 27.2 days. Embolic complications are present in 17.8% (n = 28) at diagnosis. Most cases are due to valvular infections (n = 72 cases, 45.9%). Prior cardiac surgery is documented in 49.0% (n = 77). The mean time interval for developing aortic root abscess following heart surgery is 32.2 months. 22.3% (n = 35) are immunocompromised. Aetiological agents were Staphylococcus sp. (34.1%, n = 47) and Streptococcus sp. (23.2%, n = 32). Mean antimicrobial therapy lasts 58.5 days. Outcome with surgery is superior to medical treatment: overall inpatient mortality 18.5% (n = 27); with surgery 12.2% (n = 15 out of 123 patients), with only medical management 47.8% (n = 11 out of 23 patients). In conclusion, aortic root pseudoaneurysm occurs most commonly in middle-aged male patients. History of prior aortic procedures is commonly present. Correct diagnosis hinges on detailed history, transoesophageal echocardiography, and computed tomography (CT) aorta. Surgery is the preferred therapeutic option. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01580-x.

A Transesophageal Cardiovascular Intervention.

Endoscopic ultrasonography-guided transesophageal pericardiocentesis was performed for a posteriorly located effusion not amenable to transthoracic drainage in a 58-year-old woman with a history of recurrent breast adenocarcinoma who presented with dyspnea. The patient had a pericardial effusion that resulted in cardiac tamponade. Transthoracic pericardiocentesis was unsuitable because of the posterior location of the effusion. Pericardiocentesis via the transesophageal route was performed. The pericardial sac was punctured with a 19-gauge needle, and 245 mL of pericardial fluid were aspirated, resulting in the resolution of the tamponade physiology. Endoscopic ultrasonography-guided transesophageal drainage is a novel and promising therapeutic option for posteriorly located pericardial effusions.

ARNI Versus Perindopril for Remodeling in HFrEF. A Cohort Study.

Introduction: Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly uncontrolled observational studies. There is a lack of head-to-head studies. Methods: This cohort study compares the remodeling effects of angiotensin receptor blockers combined with a neprilysin inhibitor (ARNI) and perindopril in heart failure with reduced ejection fraction (HFrEF) patients between January 2017 and December 2020. Inclusion criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed not more than 2 months prior to treatment onset, and (iv) follow-up echocardiography performed not earlier than 6 months and not later than 18 months posttreatment onset. No prior treatment with renin-angiotensin-aldosterone system inhibitors was permitted in the ARNI group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were analyzed. A two-way repeated measure ANOVA (for normally distributed) and generalized estimating equation test for nonnormally distributed interval dependent variables. Mean comparison between and within groups was performed using the Bonferroni test. Results: Following an average treatment period of 9 months, LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, increments of 11.5% and 11.8% resp. (Bonferroni test [P ≤ .05]). LVEDV was reduced by 8.4 mL and 3.2 mL, and LVESV by 17.9 mL and 10.8 mL for ARNI and perindopril resp. Only the reduction of LVESV for ARNI was statistically significant (P = .007). Conclusion: Both ARNI and perindopril yielded a significant improvement in the LVEF within 9 months. The remodeling effect of ARNI seems stronger because of the greater improvements in left ventricular volumes.

Leucine-Rich Alpha-2-Glycoprotein: A Novel Predictor of Diastolic Dysfunction.

Leucine-rich α2-glycoprotein (LRG1) mediates cardiac fibrocyte activation. It is upregulated in inflammatory conditions, atherosclerosis, and fibrosis. Diastolic dysfunction (DD) is due to myocardial fibrosis. This cross-sectional study examined the relationship between LRG1 and DD. Patients with symptoms of chronic coronary ischemia were recruited. Patients with symptoms of overt heart failure, ejection fraction (EF) < 55%, impaired renal function, infection, and recent trauma were excluded from the study. Clinical parameters examined were SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score, echocardiographic assessment, and LRG1 levels. Binary stepwise logistic regression was used to evaluate the association between LRG1 and DD. Receiver Operating Characteristic (ROC) analysis was used to determine optimal cut-off values and predictive performance of LRG1. A total of 94 patients were enrolled in the study, with 47 having a clinical diagnosis of DD. Plasma LRG1 was significantly (U = 417.00, p < 0.001) higher in the DD group (M = 14) compared to the No-DD group (M = 8) by Mann-Whitney U test. There were higher SYNTAX scores in the DD group (M = 24.5) compared with No-DD (M = 7). LRG1 had significant predictability of DD (OR = 1.32 (95% CI: 1.14-1.53)). The ROC showed an AUC = 0.89 (95% CI: 0.82-0.95). LRG1 had a 78% sensitivity (95% CI: 65.3-87.7) and 72.3% specificity (95% CI: 57.4-84.4) for predicting DD at a cut-off value of "9". In conclusion, we identified LRG1 as a novel independent predictor of DD. Further studies are warranted to validate the utility of LRG1 in predicting DD.

Whole mitochondrial genome sequencing of Malaysian patients with cardiomyopathy.

Cardiomyopathy (CMP) constitutes a diverse group of myocardium diseases affecting the pumping ability of the heart. Genetic predisposition is among the major factors affecting the development of CMP. Globally, there are over 100 genes in autosomal and mitochondrial DNA (mtDNA) that have been reported to be associated with the pathogenesis of CMP. However, most of the genetic studies have been conducted in Western countries, with limited data being available for the Asian population. Therefore, this study aims to investigate the mutation spectrum in the mitochondrial genome of 145 CMP patients in Malaysia. Long-range PCR was employed to amplify the entire mtDNA, and whole mitochondrial genome sequencing was conducted on the MiSeq platform. Raw data was quality checked, mapped, and aligned to the revised Cambridge Reference Sequence (rCRS). Variants were named, annotated, and filtered. The sequencing revealed 1,077 variants, including 18 novel and 17 CMP and/or mitochondrial disease-associated variants after filtering. In-silico predictions suggested that three of the novel variants (m.8573G>C, m.11916T>A and m.11918T>G) in this study are potentially pathogenic. Two confirmed pathogenic variants (m.1555A>G and m.11778G>A) were also found in the CMP patients. The findings of this study shed light on the distribution of mitochondrial mutations in Malaysian CMP patients. Further functional studies are required to elucidate the role of these variants in the development of CMP.

Evolving trends in infective endocarditis in a developing country: a consequence of medical progress?

BACKGROUND: Staphylococcus has replaced streptococcus as the most common cause of infective endocarditis (IE) in developed health care systems. The trend in developing countries is less clear. AIM: To examine the epidemiological trends of infective endocarditis in a developing nation. METHODS: Single-centre, retrospective study of patients admitted with IE to a tertiary hospital in Malaysia over a 12-year period. RESULTS: The analysis included 182 patients (n = 153 Duke's definite IE, n = 29 possible IE). The mean age was 51 years. Rheumatic heart disease was present in 42%, while 7.6% were immunocompromised. IE affected native valves in 171 (94%) cases. Health-care associated IE (HCAIE) was recorded in 68 (37.4%). IE admission rates increased from 25/100,000 admissions (2012) to 59/100,000 admissions (2017). At least one major complication on admission was detected in 59 (32.4%) patients. Left-sided IE was more common than right-sided IE [n = 159 (87.4%) vs. n = 18 (9.9%)]. Pathogens identified by blood culture were staphylococcus group [n = 58 (40.8%)], streptococcus group [n = 51 (35.9%)] and Enterococcus species [n = 13 (9.2%)]. staphylococcus infection was highest in the HCAIE group. In-hospital death occurred in 65 (35.7%) patients. In-hospital surgery was performed for 36 (19.8%) patients. At least one complication was documented in 163 (85.7%). CONCLUSION: Staphylococcus is the new etiologic champion, reflecting the transition of the healthcare system. Streptococcus is still an important culprit organism. The incidence rate of IE appears to be increasing. The rate of patients with underlying rheumatic heart disease is still high.

Swallow syncope: a case report and review of literature.

BACKGROUND: Swallow or deglutition syncope is an unusual type of neurally-mediated syncope associated with life-threatening bradyarrhythmia and hypotension. It is a difficult condition to diagnose with commonly delayed diagnosis and management. There is lack of review articles that elucidate the basic demographics, clinical characteristics and management of this rare condition. This publication systematically reviews the 101 case reports published since 1793 on swallow syncope. CASE PRESENTATION: A 59-year-old man presented with the complaint of recurrent dizziness associated with meals. A 24-h ambulatory ECG recording confirmed an episode of p-wave asystole at the time of food intake. Oesophagogastroduodenoscopy with balloon inflation in the mid to lower oesophagus resulted in a 5.6 s sinus pause. The patient's symptoms resolved completely following insertion of a permanent dual chamber pacemaker. CONCLUSIONS: Swallow syncope is extremely rare, but still needs to be considered during diagnostic workup. It is commonly associated with gastro-intestinal disease. Permanent pacemaker implantation is the first line treatment.

Early and aggressive ISR with a polymer- and carrier-free drug-coated stent system.

The LEADERS FREE trial concluded that the polymer free drug-coated BioFreedom™ stent appeared to be both safer and more effective than bare-metal stents (BMS) with an ISR rate comparable to traditional DES without the need for prolonged DAPT. We implanted 45 BioFreedom™ stents in 34 patients over a 4-month period. 4 patients represented early (106-238 days after the implant procedure) with angina symptoms and severe ISR was detected in all patients. The rate of severe and early ISR detected in our patient population of 11.8% is comparable to that of traditional BMS. Further studies are warranted.

Generic atorvastatin is as effective as the brand-name drug (LIPITOR®) in lowering cholesterol levels: a cross-sectional retrospective cohort study.

BACKGROUND: In a world of ever increasing health care costs, generic drugs represent a major opportunity to ensure access to essential medicines for people who otherwise would be unable to afford them. However, some clinicians and patients are still questioning the safety and effectiveness of generic formulations compared to the proprietary drugs necessitating further systematic research analyzing the generic drugs' efficacy. Our objective was to compare the lipid lowering effects of generic and branded atorvastatin. METHODS: This cross-sectional, retrospective cohort study was conducted at the University of Malaya Medical Centre from 1 May 2013 until 30 May 2013. We analyzed the lipid profiles (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) of 629 patients before and at least 3 months after switching them from proprietary atorvastatin (Lipitor®) to generic atorvastatin (atorvastatin calcium from Ranbaxy Laboratories, Inc.). We also investigated if there was any difference in the effectiveness of both atorvastatin formulations in various ethnic groups. RESULTS: 266 patients were included in this study. When comparing the median values we found no statistically significant differences (Wilcoxon signed-rank test; p < 0.05) between proprietary and generic atorvastatin in lowering total cholesterol (4.60 mmol/l pre-transition vs. 4.50 mmol/l post-transition; p = 0.583), LDL-cholesterol (2.42 mmol/l vs. 2.41 mmol/l; p = 0.923) and triglycerides (1.50 mmol/l vs. 1.50 mmol/l; p = 0.513). While there was a statistically significant (p = 0.009) difference in HDL-cholesterol levels favouring proprietary atorvastatin, the extent of this change (1.26 mmol/l vs. 1.25 mmol/l) was deemed not to be clinically relevant. There was no statistically significant difference when analyzing the effects on various ethnic groups. CONCLUSIONS: Substituting proprietary atorvastatin for its generic formulation atorvastatin calcium does not result in a less effective management of hyperlipidemia. Our findings lend support to the approach of lowering health care costs by switching patients from branded drugs to their less expensive generic analogues.

Characterization of single cell derived cultures of periosteal progenitor cells to ensure the cell quality for clinical application.

For clinical applications of cells and tissue engineering products it is of importance to characterize the quality of the used cells in detail. Progenitor cells from the periosteum are already routinely applied in the clinics for the regeneration of the maxillary bone. Periosteal cells have, in addition to their potential to differentiate into bone, the ability to develop into cartilage and fat. However, the question arises whether all cells isolated from periosteal biopsies are able to differentiate into all three tissue types, or whether there are subpopulations. For an efficient and approved application in bone or cartilage regeneration the clarification of this question is of interest. Therefore, 83 different clonal cultures of freshly isolated human periosteal cells derived from mastoid periosteum biopsies of 4 donors were generated and growth rates calculated. Differentiation capacities of 51 clonal cultures towards the osteogenic, the chondrogenic, and the adipogenic lineage were investigated. Histological and immunochemical stainings showed that 100% of the clonal cultures differentiated towards the osteogenic lineage, while 94.1% demonstrated chondrogenesis, and 52.9% could be stimulated to adipogenesis. For osteogenesis real-time polymerase chain reaction (PCR) of BGLAP and RUNX2 and for adipogenesis of FABP4 and PPARG confirmed the results. Overall, 49% of the cells exhibited a tripotent potential, 45.1% showed a bipotent potential (without adipogenic differentiation), 3.9% bipotent (without chondrogenic differentiation), and 2% possessed a unipotent osteogenic potential. In FACS analyses, no differences in the marker profile of undifferentiated clonal cultures with bi- and tripotent differentiation capacity were found. Genome-wide microarray analysis revealed 52 differentially expressed genes for clonal subpopulations with or without chondrogenic differentiation capacity, among them DCN, NEDD9, TGFBR3, and TSLP. For clinical applications of periosteal cells in bone regeneration all cells were inducible. For a chondrogenic application a fraction of 6% of the mixed population could not be induced.

The SPEED (sepsis patient evaluation in the emergency department) score: a risk stratification and outcome prediction tool.

OBJECTIVES: The aim of the study was to identify covariates associated with 28-day mortality in septic patients admitted to the emergency department and derive and validate a score that stratifies mortality risk utilizing parameters that are readily available. METHODS: Patients with an admission diagnosis of suspected or confirmed infection and fulfilling at least two criteria for severe inflammatory response syndrome were included in this study. Patients' characteristics, vital signs, and laboratory values were used to identify prognostic factors for mortality. A scoring system was derived and validated. The primary outcome was the 28-day mortality rate. RESULTS: A total of 440 patients were included in the study. The 28-day hospital mortality rate was 32.4 and 25.2% for the derivation (293 patients) and validation (147 patients) sets, respectively. Factors associated with a higher mortality were immune-suppressed state (odds ratio 4.7; 95% confidence interval 2.0-11.4), systolic blood pressure on arrival less than 90 mmHg (3.8; 1.7-8.3), body temperature less than 36.0°C (4.1; 1.3-12.9), oxygen saturation less than 90% (2.3; 1.1-4.8), hematocrit less than 0.38 (3.1; 1.6-5.9), blood pH less than 7.35 (2.0; 1.04-3.9), lactate level more than 2.4 mmol/l (2.27; 1.2-4.2), and pneumonia as the source of infection (2.7; 1.5-5.0). The area under the receiver operating characteristic curve was 0.81 (0.75-0.86) in the derivation and 0.81 (0.73-0.90) in the validation set. The SPEED (sepsis patient evaluation in the emergency department) score performed better (P=0.02) than the Mortality in Emergency Department Sepsis score when applied to the complete study population with an area under the curve of 0.81 (0.76-0.85) as compared with 0.74 (0.70-0.79). CONCLUSION: The SPEED score predicts 28-day mortality in septic patients. It is simple and its predictive value is comparable to that of other scoring systems.

Performance of emergency physicians in point-of-care echocardiography following limited training.

OBJECTIVES: The aim of this study was to evaluate if emergency medicine trainees with a short duration of training in echocardiography could perform and interpret bedside-focused echocardiography reliably on emergency department patients. METHODS: Following a web-based learning module and 3 h of proctored practical training, emergency medicine trainees were evaluated in technical and interpretative skills in estimating left ventricular function, detection of pericardial effusion and inferior vena cava (IVC) diameter measurements using bedside-focused echocardiography on emergency department patients. An inter-rater agreement analysis was performed between the trainees and a board-certified cardiologist. RESULTS: 100 focused echocardiography examinations were performed by nine emergency medicine trainees. Agreement between the trainees and the cardiologist was 93% (K=0.79, 95% CI 0.773 to 0.842) for visual estimation of left ventricular function, 92.9% (K=0.80, 95% CI 0.636 to 0.882) for quantitative left ventricular ejection fraction by M-mode measurements, 98% (K=0.74, 95% CI 0.396 to 1.000) for the detection of pericardial effusion, and 64.2% (K=0.45, 95% CI 0.383 to 0.467) for IVC diameter assessment. The Bland-Altman limits of agreement for left ventricular function was -9.5% to 13.7%, and a Pearson's correlation yielded a value of 0.82 (p<0.0001, 95% CI 0.734 to 0.881). The trainees detected pericardial effusion with a sensitivity of 60%, specificity of 100%, positive predictive value of 100% and negative predictive value of 97.9%. CONCLUSIONS: Emergency medicine trainees were found to be able to perform and interpret focused echocardiography reliably after a short duration of training.