Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular ...diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium–glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype‐based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence‐based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy.
Tuberculosis (TB), known with several other names such as Tapedik, Kshay Rog, phthisis, consumption, white death, great white plague, graveyard cough, King's Evil, etc., is documented since 3000 ...years BC and some workers rightly consider it a disease of antiquity. However, the pathogen causing this disease (Mycobacterium tuberculosis) was discovered and named 133 years back on this day by Dr. Robert Koch.
We present a rare case of a patient with toluene exposure manifesting as anti-glomerular basement membrane (GBM) disease on a background of phospholipase A
receptor (PLA
R)-associated membranous ...nephropathy. A 23-year-old man presented to the emergency department with hypertension, headache, hemoptysis, anemia, acute kidney injury, glomerular hematuria, and proteinuria. He endorsed repeated exposure to toluene-containing products while repairing dirt bikes. Serologies were positive for anti-GBM antibodies. Kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G and granular PLA
R staining by immunofluorescence. He was initially treated with high-dose steroids, plasmapheresis, and hemodialysis for pulmonary-renal syndrome followed by oral cyclophosphamide and prednisone, which were discontinued after 3 months when follow-up biopsies confirmed little chance for renal recovery. He remained on dialysis 1 year later. This case exhibits a unique presentation of anti-GBM syndrome and underlying membranous nephropathy following repeated hydrocarbon exposure. Inhaled toxins promote recurrent localized inflammation, unmasking previously hidden epitopes. Early diagnosis and appropriate use of immunosuppressive and extracorporeal therapies are necessary to prevent morbidity and to improve survival in this rare condition.
Among patients hospitalized for acute myocardial infarction and at risk for heart failure, empagliflozin did not lead to a significantly lower risk of a first heart-failure hospitalization or death ...from any cause than placebo.
Background:There are concerns that Asian patients respond differently to some medications. This study evaluated the efficacy and safety of evolocumab among Asian vs. other subjects in the FOURIER ...trial, which randomized stable atherosclerosis patients to receive either evolocumab or placebo.Methods and Results:Effects of adding evolocumab vs. placebo to background statin therapy on low-density lipoprotein cholesterol (LDL-C) reductions, cardiovascular outcomes, and adverse events were compared among 27,564 participants with atherosclerotic disease, according to self-reported Asian (n=2,723) vs. other (n=24,841) races followed for a median of 2.2 years in the FOURIER trial. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. At randomization, Asians had slightly lower LDL-C (median 89 IQR 78–104 mg/dL vs. 92 80–109 mg/dL; P<0.001) and were much less likely to be on a high-intensity statin (33.3% vs. 73.3%; P<0.001). Evolocumab lowered LDL-C more in Asians than in others (66% vs. 58%; P<0.001). The effect of evolocumab on the primary endpoint was similar in Asians (HR, 0.79; 95% CI, 0.61–1.03) and others (HR, 0.86; 95% CI, 0.79–0.93; P interaction=0.55). There was no excess of serious adverse events with evolocumab among Asians over others.Conclusions:Use of evolocumab robustly lowers LDL-C and is equally efficacious in lowering the risk of cardiovascular events and safe in Asians as it is in others.
Presence of ischemic heart disease impacts prognosis in patients affected by heart failure and reduced ejection fraction (HFrEF). It is not well known how the extent of vascular disease impacts ...prognosis and response to therapy in this setting.
In this post hoc analysis of the EMPEROR-Reduced trial, outcomes, and the effect of empagliflozin, were assessed in study participants according to the extent (none vs. mono 1 vs. poly ≥2 vascular bed) of vascular disease. Vascular disease was defined as investigator-reported coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular disease at baseline. Cox proportional-hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Incidence rates are presented per 100 person-years (py) of follow-up.
Of the 3,730 study participants enrolled, 1324 (35.5%) had no, 1879 (50.4%) had mono, and 527 (14.1%) had poly-vascular disease. Participants with poly-vascular disease tended to be older, male, and with history of hypertension, diabetes, and smoking. In the placebo arm, a significant higher risk for cardiovascular death existed in those with poly-vascular disease (HR1.57, 95%CI 1.02, 2.44 compared to no vascular disease). In adjusted analysis, the benefit of empagliflozin on cardiovascular death or HF hospitalization, HF hospitalization, cardiovascular death, renal composite endpoint, estimated glomerular filtration slope changes, and health status scores, were seen across the three groups (interaction P>0.05 for all) but were attenuated in those with poly-vascular disease. Adverse events were higher in those with poly-vascular disease but there were no major differences noted between empagliflozin or placebo assignment in the three groups.
In patients with HFrEF, the extent of vascular disease is associated with the risk for adverse cardiovascular outcomes. Empagliflozin offers cardiovascular and renal benefits in HFrEF across the extent of vascular disease, but this benefit is attenuated in those with poly-vascular disease.
A 25-year-old man presenting with peripheral and cerebral emboli was incidentally detected as having a left ventricular mass on two-dimensional echocardiographic examination of the heart. In absence ...of any obvious structural heart disease or hypercoagulable state, the mass was presumptively diagnosed as left ventricular myxoma. The patient was operated on, and histopathology revealed the mass to be a thrombus. The cause and pathogenesis of the left ventricular thrombus, differential diagnosis, and management are discussed. The rarity of the case is highlighted.
Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the host genetic background plays an important role toward the disease pathogenesis. Various studies have identified a ...number of human genes in association with leprosy or its clinical forms. However, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved LD structures and differential frequencies of SNPs within the studied regions of the genome. A need for systematic and saturated mapping of the associated regions with the disease is warranted to unravel the observed heterogeneity in different populations. Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. The association was replicated in a geographically distinct and unrelated population from Orissa in eastern India. In vitro reporter assays revealed that the two significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and represented in a single BIN of 8 SNPs, influenced the gene expression. A comparison of BINs between Indian and Vietnamese populations revealed differences in the BIN structures, explaining the heterogeneity and also the reason for non-replication of the associated genomic region in different populations.
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