A common polymorphism of the human cardiac sodium channel alpha subunit (SCN5A) gene is associated with sudden cardiac death in chronic ischemic heart disease

Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio =1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association. © 2015 Marcsa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Spironolactone improves endothelial and cardiac autonomic function in non heart failure hemodialysis patients

OBJECTIVES: Hemodialysis patients have a cardiovascular mortality rate of 20-40 times that of the general population. Aldosterone inhibition by spironolactone has exerted beneficial, prognostically significant cardiovascular effects in patients with heart failure maintained on hemodialysis or peritoneal dialysis. Our aim was to investigate spironolactone\u27s effect in non heart failure hemodialysis patients. METHODS: Fourteen stable chronic hemodialysis patients (nine men), 59.5 +/- 3.1 years of age were evaluated in a sequential, fixed-dose, placebo-controlled study. Heart failure was diagnosed on the basis of signs and symptoms of heart failure or left ventricular ejection fraction less than 50%. Following an initial 4-month period of placebo administration after each dialysis, patients received spironolactone (25 mg thrice weekly after dialysis) for the next 4 months. Data were recorded at baseline, at the end of placebo administration, and at the end of spironolactone treatment and included endothelial function by forearm reactive hyperemia during venous occlusion plethysmography, cardiac autonomic status by heart rate variability in the time and frequency domain, blood pressure response, and echocardiographic and laboratory data. RESULTS: Placebo induced no changes in the aforementioned parameters. Following spironolactone, salutary effects were observed in the extent and duration of reactive hyperemia (P < 0.05 for both), as well as in heart rate variability (P < 0.05) and blood pressure control (P < 0.05). No changes occurred in echocardiographically derived left ventricular dimensions or mass. CONCLUSION: Low-dose spironolactone therapy in clinically stable non heart failure hemodialysis patients is associated with favorable effects on cardiovascular parameters known to adversely affect survival, such as endothelial dysfunction and heart rate variability. Spironolactone treatment might benefit long-term cardiovascular outcome of such patients

COVID- 19 in patients affected by red blood cell disorders, results from the European registry ERN-EuroBloodNet

Background: Despite several publications covering patients from multiple centers, no international registry covered all patients with red blood cell diseases (RBCD) affected by COVID- 19. The ERN-EuroBloodNet's registry provided real-time registration of SARS-CoV- 2 patients with RBCD, promoting timely disease-specific knowledge sharing during the pandemic's early stages. Procedures: The study evaluated patient distribution, the infection across different RBCDs, and severity risk factors across similar healthcare systems, using data collected from the ERN-EuroBloodNet's REDCap platform. Results: From April 2020 to April 2023, 681 infections were recorded among 663 patients, of which 373 had transfusion-dependent thalassemia or non-transfusion-dependent thalassemia (TDT/NTDT), and 269 had sickle cell disease (SCD). SCD patients had a higher incidence of COVID- 19 than those with TDT/NTDT (10.5 vs. 4.8 COVID/100 patients). Notably, 92% of the cases were mild, with neither age nor the specific RBCD affecting severity. The number of comorbidities, notably obesity and hypertension, that patients had prior to infection was associated with more severe COVID- 19. During the infection, the presence of vaso-occlusive crises, acute chest syndrome, kidney failure, and ground-glass opacities on chest tomography scans were associated with a more severe clinical picture. The vaccination rate (32%) mirrored that of the general population and showed a protective effect against severe COVID- 19. The observed mortality rate was 0.7%, aligning with Europe's general population. Conclusion: SARS-CoV- 2 infection in SCD and TDT/NTDT patients is mild and without higher mortality than the general population. The ERN-Eurobloodnet’s registry collaborative structure exemplifies the power of international cooperation in tackling rare diseases, especially during health emergencies

Usefulness of NT-pro BNP monitoring to identify echocardiographic responders following cardiac resynchronization therapy

<p>Abstract</p> <p>Background</p> <p>Cardiac resynchronization therapy (CRT) improves left ventricular (LV) volumes, mitral regurgitation (MR) severity and symptoms of patients with heart failure (HF). However, ≥ 30% of patients have no significant clinical or echocardiographic improvement following CRT. Reverse remodeling after CRT correlates with improved clinical outcomes. We hypothesized that in NT-pro BNP monitoring is accurate to identify responders following CRT.</p> <p>Methods</p> <p>42 consecutive patients (mean age 66 ± 12 years, male 68%) with HF undergoing CRT were prospectively enrolled. Responders at follow-up were defined by echocardiography (decrease in LV end systolic volume ≥ 15%). Echocardiography and NT-pro BNP measurement were performed at baseline and repeated 3 to 6 month after CRT.</p> <p>Results</p> <p>There was no significant difference between responders (n = 29, 69%) and non-responders (n = 13, 31%) regarding baseline NT-pro BNP level. Responders had significantly higher decrease in NT-pro BNP levels during follow-up than non-responders (absolute: -1428 ± 1333 pg.ml^-1vs. -61 ± 959 pg.ml^-1, p = 0.002; relative: -45 ± 28% vs. 2 ± 28%, p < 0.0001). A decrease of ≥ 15% in NT-pro BNP 3–6 months after CRT identifies echocardiographic responders with a sensitivity of 90% and a specificity of 77%.</p> <p>Conclusion</p> <p>NT-pro BNP monitoring can accurately identify echocardiographic responders after CRT.</p

COVID- 19 in patients affected by red blood cell disorders, results from the European registry ERN-EuroBloodNet

Background: Despite several publications covering patients from multiple centers, no international registry covered all patients with red blood cell diseases (RBCD) affected by COVID- 19. The ERN-EuroBloodNet's registry provided real-time registration of SARS-CoV- 2 patients with RBCD, promoting timely disease-specific knowledge sharing during the pandemic's early stages. Procedures: The study evaluated patient distribution, the infection across different RBCDs, and severity risk factors across similar healthcare systems, using data collected from the ERN-EuroBloodNet's REDCap platform. Results: From April 2020 to April 2023, 681 infections were recorded among 663 patients, of which 373 had transfusion-dependent thalassemia or non-transfusion-dependent thalassemia (TDT/NTDT), and 269 had sickle cell disease (SCD). SCD patients had a higher incidence of COVID- 19 than those with TDT/NTDT (10.5 vs. 4.8 COVID/100 patients). Notably, 92% of the cases were mild, with neither age nor the specific RBCD affecting severity. The number of comorbidities, notably obesity and hypertension, that patients had prior to infection was associated with more severe COVID- 19. During the infection, the presence of vaso-occlusive crises, acute chest syndrome, kidney failure, and ground-glass opacities on chest tomography scans were associated with a more severe clinical picture. The vaccination rate (32%) mirrored that of the general population and showed a protective effect against severe COVID- 19. The observed mortality rate was 0.7%, aligning with Europe's general population. Conclusion: SARS-CoV- 2 infection in SCD and TDT/NTDT patients is mild and without higher mortality than the general population. The ERN-Eurobloodnet’s registry collaborative structure exemplifies the power of international cooperation in tackling rare diseases, especially during health emergencies.</p

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Abstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Clinical effectiveness of primary prevention implantable cardioverter-defibrillators: results of the EU-CERT-ICD controlled multicentre cohort study

Aims  The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy. Methods and results  We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537–0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class <III, and chronic obstructive pulmonary disease. Adjusted mortality associated with ICD vs. control was 27% lower (HR 0.731, 95% CI 0.569–0.938, P = 0.0140). Subgroup analyses indicated no ICD benefit in diabetics (adjusted HR = 0.945, P = 0.7797, P for interaction = 0.0887) or those aged ≥75 years (adjusted HR 1.063, P = 0.8206, P for interaction = 0.0902). Conclusion  In contemporary ICM/DCM patients (LVEF ≤35%, narrow QRS), primary prophylactic ICD treatment was associated with a 27% lower mortality after adjustment. There appear to be patients with less survival advantage, such as older patients or diabetics