Atypical symptoms with typical signs in a patient with Propionibacterium acnes related mitral valve endocarditis

Infective endocarditis (IE) is a serious medical condition associated with an increase in morbidity and mortality if not treated promptly and adequately. The clinical outcome depends on the early diagnosis and aggressiveness of the causative organism. Patients usually present with typical features suggestive of Infective endocarditis but in some circumstances the presentations are atypical, and if not diagnosed and treated, may lead to serious consequences. We present a case of atypical presentations of infective endocarditis caused by Propionibacterium acnes organism with no classical features of endocarditis and had symptoms suggestive of urinary tract infection. The diagnosis of IE can be very difficult in patients with atypical clinical presentation, particularly caused by low-pathogenicity organisms. Appropriate clinical assessment and high level of suspicious especially in the patients with previous history of infective endocarditis or having prosthetic valves in situ is crucial

Effects of the coronary artery disease associated LPA and 9p21 loci on risk of aortic valve stenosis

Background: Aortic valve stenosis (AVS) and coronary artery disease (CAD) have a significant genetic contribution and commonly co-exist. To compare and contrast genetic determinants of the two diseases, we investigated associations of the LPA and 9p21 loci, i.e. the two strongest CAD risk loci, with risk of AVS. Methods: We genotyped the CAD-associated variants at the LPA (rs10455872) and 9p21 loci (rs1333049) in the GeneCAST (Genetics of Calcific Aortic STenosis) Consortium and conducted a meta-analysis for their association with AVS. Cases and controls were stratified by CAD status. External validation of findings was undertaken in five cohorts including 7880 cases and 851,152 controls. Results: In the meta-analysis including 4651 cases and 8231 controls the CAD-associated allele at the LPA locus was associated with increased risk of AVS (OR 1.37; 95%CI 1.24–1.52, p = 6.9 × 10−10) with a larger effect size in those without CAD (OR 1.53; 95%CI 1.31–1.79) compared to those with CAD (OR 1.27; 95%CI 1.12–1.45). The CAD-associated allele at 9p21 was associated with a trend towards lower risk of AVS (OR 0.93; 95%CI 0.88–0.99, p = 0.014). External validation confirmed the association of the LPA risk allele with risk of AVS (OR 1.37; 95%CI 1.27–1.47), again with a higher effect size in those without CAD. The small protective effect of the 9p21 CAD risk allele could not be replicated (OR 0.98; 95%CI 0.95–1.02). Conclusions: Our study confirms the association of the LPA locus with risk of AVS, with a higher effect in those without concomitant CAD. Overall, 9p21 was not associated with AVS

Surgical or percutaneous repair of sinus of valsalva rupture: Case series and literature review

The rupture of the sinus of the Valsalva aneurysm is a rare but very serious condition. Rapid and accurate diagnosis and prompt treatment are critical for these cases. We present two cases of sinus of Valsalva ruptures. One case was managed with open surgical repair and the second case was treated percutaneously. We have discussed these two therapeutic approaches available to treat sinus of Valsalva rupture

Mackay Heart Failure Study: Examining the Root Causes, Compliance With Guideline-Based Therapy and Prognosis

Introduction: Heart failure patients have poor outcomes comparable to some malignancies; however, the modern guideline directed medical therapy (GDMT) has improved its outcomes. The clinical characteristics and prescribers’ compliance with GDMT for heart failure patients have not been studied in the Mackay region. Methods: A retrospective cohort study of 115 consecutive adult heart failure patients was conducted at our institution. Results: The study cohort consisted of 80% (n=92) males. Ischaemia was the leading cause accounting for 54% (n=62) of the cohort, followed by idiopathic cardiomyopathy at 32% (n=37). Drug-induced and Takotsubo cardiomyopathies were responsible for 11% and 1% respectively. Two (2) patients (2%) had valvular heart disease. Hypertension was present in 57% while diabetes and atrial fibrillation were present in 32% and 43% of patients. Fifty-nine per cent (59%) had a smoking history. All, except four patients, had reduced left ventricular ejection fraction (LVEF <50%) at diagnosis. Among patients with coronary ischaemia, 37% and 31% were revascularised with percutaneous coronary interventions and bypass graft surgeries, respectively. Renin-angiotensin-aldosterone system inhibitors and beta blockers were prescribed in 94% and 95% of the patients, respectively. Mineralocorticoid inhibitors were used in 25% while ivabradine was given to 8% of patients. Nine per cent (9%) of patients received cardiac resynchronisation therapy. Most patients had improvement in functional class and LVEF during follow-up. There were very few mortalities at 3% (n=3) at the median follow-up of 403 (IQR 239–896) days. Conclusion: Our study has shed light on heart failure epidemiology in the Mackay region. We found excellent compliance with GDMT and good prognosis for most patients in terms of both symptom and survival

Post-Genomic Update on a Classical Candidate Gene for Coronary Artery Disease: ESR1

BACKGROUND: After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated. METHODS AND RESULTS: We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87,000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1. In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. CONCLUSIONS: We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system

Large-Scale Analysis of Determinants, Stability, and Heritability of High-Density Lipoprotein Cholesterol Efflux Capacity.

OBJECTIVE: Cholesterol efflux capacity (CEC) has emerged as a biomarker of coronary artery disease risk beyond plasma high-density lipoprotein (HDL) cholesterol (HDL-C) level. However, the determinants of CEC are incompletely characterized. We undertook a large-scale family-based population study to identify clinical, biochemical, and HDL particle parameter determinants of CEC, characterize reasons for the discordancy with HDL-C, quantify its heritability, and assess its stability over 10 to 12 years. APPROACHES AND RESULTS: CEC was quantified in 1988 individuals from the GRAPHIC (Genetic Regulation of Arterial Pressure of Humans in the Community) cohort, comprising individuals from 2 generations from 520 white nuclear families. Serum lipid and lipoprotein levels were determined by ultracentrifugation or nuclear magnetic resonance and HDL particle size and number quantified by nuclear magnetic resonance. Ninety unrelated individuals had repeat CEC measurements in samples collected after 10 to 12 years. CEC was positively correlated with HDL-C (R=0.62; P<0.0001). Among clinical and biochemical parameters, age, systolic blood pressure, alcohol consumption, serum albumin, triglycerides, phospholipids, and lipoprotein(a) were independently associated with CEC. Among HDL particle parameters, HDL particle number, particle size, and apolipoprotein A-II level were independently associated with CEC. Serum triglyceride level partially explained discordancy between CEC and HDL-C. CEC measurements in samples collected 10 to 12 years apart were strongly correlated (r=0.73; P<0.0001). Heritability of CEC was 0.31 (P=3.89×10(-14)) without adjustment for HDL-C and 0.13 (P=1.44×10(-3)) with adjustment. CONCLUSIONS: CEC is a stable trait over time, is influenced by specific clinical, serum, and HDL particle parameters factors beyond HDL-C, can be maintained in persons with a low plasma HDL-C by elevated serum triglyceride level, and is modestly independently heritable

Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease.

OBJECTIVE: Only a small fraction of coronary artery disease (CAD) heritability has been explained by common variants identified to date. Interactions between genes of importance to cardiovascular regulation may account for some of the missing heritability of CAD. This study aimed to investigate the role of gene-gene interactions in common variants in candidate cardiovascular genes in CAD. APPROACH AND RESULTS: 2,101 patients with CAD from the British Heart Foundation Family Heart Study and 2,426 CAD-free controls were included in the discovery cohort. All subjects were genotyped with the Illumina HumanCVD BeadChip enriched for genes and pathways relevant to the cardiovascular system and disease. The primary analysis in the discovery cohort examined pairwise interactions among 913 common (minor allele frequency >0.1) independent single nucleotide polymorphisms (SNPs) with at least nominal association with CAD in single locus analysis. A secondary exploratory interaction analysis was performed among all 11,332 independent common SNPs surviving quality control criteria. Replication analyses were conducted in 2,967 patients and 3,075 controls from the Myocardial Infarction Genetics Consortium. None of the interactions amongst 913 SNPs analysed in the primary analysis was statistically significant after correction for multiple testing (required P 1.7 for common variants in the primary analysis. CONCLUSIONS: Moderately large additive interactions between common SNPs in genes relevant to cardiovascular disease do not appear to play a major role in genetic predisposition to CAD. The role of genetic interactions amongst less common SNPs and with medium and small magnitude effects remain to be investigated