In standard reference sources, the incidence of coronary artery disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and 46.5%. Since then, the incidence of cardiovascular risk ...factors (CRF) has increased and modern treatment strategies ("pill in the pocket") are only applicable to patients without structural heart disease. The aim of this study was to investigate the incidence and severity of CAD in patients with AF.
From January 2005 until December 2009, we included 261 consecutive patients admitted to hospital with paroxysmal, persistent or permanent AF in this prospective study. All patients underwent coronary angiography and the Framingham risk score (FRS) was calculated. Patients with previously diagnosed or previously excluded CAD were excluded.
The overall incidence of CAD in patients presenting with AF was 34%; in patients >70 years, the incidence of CAD was 41%. The incidence of patients undergoing a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) was 21%. Patients with CAD were older (73±8 years vs 68±10 years, p = 0.001), had significantly more frequent hypercholesterolemia (60% vs 30%, p<0.001), were more frequent smokers (26% vs 13%, p = 0.017) and suffered from angina more often (37% vs 2%, p<0.001). There was a significant linear trend among the FRS categories in percentage and the prevalence of CAD and PCI/CABG (p<0.0001).
The overall incidence of CAD in patients presenting with AF was relatively high at 34%; the incidence of PCI/CABG was 21%. Based upon increasing CRF in the western world, we recommend a careful investigation respecting the FRS to either definitely exclude or establish an early diagnosis of CAD--which could contribute to an early and safe therapeutic strategy considering type Ic antiarrhythmics and oral anticoagulation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to evaluate the diagnostic and prognostic value of presepsin in patients with severe sepsis and septic shock during the first week of ICU treatment.
In total, 116 patients ...with suspected severe sepsis or septic shock were included during the first 24 hours of ICU treatment. Blood samples for biomarker measurements of presepsin, procalcitonin (PCT), interleukin 6 (IL-6), C reactive protein (CRP) and white blood cells (WBC) were drawn at days 1, 3 and 8. All patients were followed up for six months. Biomarkers were tested for diagnosis of sepsis, severe sepsis, septic shock and for prognosis of 30-days and 6-months all-cause mortality at days 1, 3 and 8. Diagnostic and prognostic utilities were tested by determining diagnostic cutoff levels, goodness criteria, C-statistics and multivariable Cox regression models.
Presepsin increased significantly from the lowest to most severe sepsis groups at days 1, 3 and 8 (test for linear trend P <0.03). Presepsin levels revealed valuable diagnostic capacity to diagnose severe sepsis and septic shock at days 1, 3 and 8 (range of diagnostic area under the curves (AUC) 0.72 to 0.84, P = 0.0001) compared to IL-6, PCT, CRP and WBC. Goodness criteria for diagnosis of sepsis severity were analyzed (≥sepsis, cutoff = 530 pg/ml; ≥severe sepsis, cutoff = 600 pg/ml; ≥septic shock, cutoff = 700 pg/ml; P <0.03). Presepsin levels revealed significant prognostic value for 30 days and 6 months all-cause mortality (presepsin: range of AUC 0.64 to 0.71, P <0.02). Patients with presepsin levels of the 4th quartile were 5 to 7 times more likely to die after six months than patients with lower levels. The prognostic value for all-cause mortality of presepsin was comparable to that of IL-6 and better than that of PCT, CRP or WBC.
In patients with suspected severe sepsis and septic shock, presepsin reveals valuable diagnostic capacity to differentiate sepsis severity compared to PCT, IL-6, CRP, WBC. Additionally, presepsin and IL-6 reveal prognostic value with respect to 30 days and 6 months all-cause mortality throughout the first week of ICU treatment.
ClinicalTrials.gov http://NCT01535534. Registered 14 February 2012.
Abstract Background BrS is an inherited sudden cardiac death syndrome. Less than 35% of BrS probands have genetically identified pathogenic variants. Recent evidence has implicated SCN10A , a ...neuronal sodium channel gene encoding Nav 1.8, in the electrical function of the heart. Objectives The purpose of this study was to test the hypothesis that SCN10A variants contribute to the development of Brugada syndrome (BrS). Methods Clinical analysis and direct sequencing of BrS susceptibility genes were performed for 150 probands and family members as well as >200 healthy controls. Expression and coimmunoprecipitation studies were performed to functionally characterize the putative pathogenic mutations. Results We identified 17 SCN10A mutations in 25 probands (20 male and 5 female); 23 of the 25 probands (92.0%) displayed overlapping phenotypes. SCN10A mutations were found in 16.7% of BrS probands, approaching our yield for SCN5A mutations (20.1%). Patients with BrS who had SCN10A mutations were more symptomatic and displayed significantly longer PR and QRS intervals compared with SCN10A -negative BrS probands. The majority of mutations localized to the transmembrane-spanning regions. Heterologous coexpression of wild-type (WT) SCN10A with WT- SCN5A in HEK cells caused a near doubling of sodium channel current compared with WT -SCN5A alone. In contrast, coexpression of SCN10A mutants (R14L and R1268Q) with WT- SCN5A caused a 79.4% and 84.4% reduction in sodium channel current, respectively. The coimmunoprecipitation studies provided evidence for the coassociation of Nav 1.8 and Nav 1.5 in the plasma membrane. Conclusions Our study identified SCN10A as a major susceptibility gene for BrS, thus greatly enhancing our ability to genotype and risk stratify probands and family members.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To prospectively evaluate radiation and contrast medium requirements for performing high-pitch coronary computed tomographic (CT) angiography at 70 kV using a third-generation dual-source CT system ...in comparison to a second-generation dual-source CT system.
All patients gave informed consent for this institutional review board-approved study. Forty-five patients (median age, 52 years; 27 men) were imaged in high-pitch mode with a third-generation dual-source CT system at 70 kV (n = 15) or with a second-generation dual-source CT system at 80 or 100 kV (n = 15 for each). Tube voltage was based on body mass index: 80 or 70 kV for less than 26 kg/m(2) versus 100 kV for 26-30 kg/m(2). For the 80- and 100-kV protocols, 80 mL of contrast material was injected, versus 45 mL for the 70-kV protocol. Data were reconstructed by using a second-generation iterative reconstruction algorithm for second-generation dual-source CT and a recently introduced third-generation iterative reconstruction algorithm for third-generation dual-source CT. Objective image quality was measured for various regions of interest, and subjective image quality was evaluated with a five-point Likert scale.
The signal-to-noise ratio of the coronary CT angiography studies acquired with 70 kV was significantly higher (70 kV: 14.3-17.6 vs 80 kV: 7.1-12.9 vs 100 kV: 9.8-12.9; P < .0497) than those acquired with the other two protocols for all coronary arteries. Qualitative image quality analyses revealed no significant differences between the three CT angiography protocols (median score, 5; P > .05). The mean effective dose was 75% and 108% higher (0.92 mSv ± 0.3 standard deviation and 0.78 mSv ± 0.2 vs 0.44 mSv ± 0.1; P < .0001), respectively, for the 80- and 100-kV CT angiography protocols than for the 70-kV CT angiography protocol.
In nonobese patients, third-generation high-pitch coronary dual-source CT angiography at 70 kV results in robust image quality for studying the coronary arteries, at significantly reduced radiation dose (0.44 mSv) and contrast medium volume (45 mL), thus enabling substantial radiation dose and contrast medium savings as compared with second-generation dual-source CT.
Abstract Background Heart Failure (HF) is increasing in prevalence and is a major cause of morbidity and mortality, despite advances in medical and device therapy. Autonomic imbalance, with excess ...sympathetic activation and decreased vagal tone, is an integral component of the pathophysiology of HF. Objectives INOVATE-HF was designed to assess the safety and efficacy of vagal nerve stimulation (VNS) among patients with heart failure and a reduced ejection fraction. Methods INOVATE-HF was a multinational, randomized trial involving 85 centers in patients with chronic HF, NYHA III symptoms and ejection fraction < 40%. Patients were assigned to device implantation to provide VNS (Active) or continued medical therapy (Control) in a 3:2 ratio. The primary efficacy endpoint was the composite of death from any cause or first event for worsening HF. Results There were 707 patients randomized and followed for a mean of 16 months. The primary efficacy outcome occurred in 132 of 436 patients in the VNS group, as compared with 70 of 271 in the control group (30.3% vs. 25.8%; hazard ratio, 1.14; 95% confidence interval CI, 0.86 to 1.53; P = 0.37). During the trial, the estimated annual mortality rates of 9.3% and 7.1%, respectively (p=0.19). Quality of life, New York Heart Association Class and 6 minute walking distance were favorably affected by VNS (p’s < 0.05), but left ventricular end-systolic volume index was not different (P=0.49). Conclusions VNS does not reduce the rate of death or HF events in chronic HF patients. (Clinical Trials.gov number NCT01303718)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular ...(LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy.
This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients age 56 ± 11 years, LV ejection fraction (LVEF) 23 ± 8%. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 ± 76 to 471 ± 111 m), LVEF (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year.
This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.
Abstract Brugada syndrome is an inherited heart disease without structural abnormalities that is thought to arise as a result of accelerated inactivation of Na channels and predominance of transient ...outward K current ( Ito ) to generate a voltage gradient in the right ventricular layers. This gradient triggers ventricular tachycardia/ventricular fibrillation possibly through a phase 2 reentrant mechanism. The Brugada electrocardiographic (ECG) pattern, which can be dynamic and is sometimes concealed, being only recorded in upper precordial leads, is the hallmark of Brugada syndrome. Because of limitations of previous consensus documents describing the Brugada ECG pattern, especially in relation to the differences between types 2 and 3, a new consensus report to establish a set of new ECG criteria with higher accuracy has been considered necessary. In the new ECG criteria, only 2 ECG patterns are considered: pattern 1 identical to classic type 1 of other consensus (coved pattern) and pattern 2 that joins patterns 2 and 3 of previous consensus (saddle-back pattern). This consensus document describes the most important characteristics of 2 patterns and also the key points of differential diagnosis with different conditions that lead to Brugada-like pattern in the right precordial leads, especially right bundle-branch block, athletes, pectus excavatum, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Also discussed is the concept of Brugada phenocopies that are ECG patterns characteristic of Brugada pattern that may appear and disappear in relation with multiple causes but are not related with Brugada syndrome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an ...endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide (LPS) in different concentrations for different times. ELISA, FACS, qPCR, and patch-clamp techniques were used for the study. TLR4 (Toll-like receptor 4) and its associated proteins, CD14, LBP (lipopolysaccharide binding protein), TIRAP (toll-interleukin 1 receptor domain containing adaptor protein), Ly96 (lymphocyte antigen 96) and nuclear factor kappa B as well as some pro-and anti-inflammatory factors are expressed in hiPSC-CMs. LPS-treatment for 6 hours increased the expression levels of pro-inflammatory and chemotactic cytokines (TNF-a, IL-1ß, IL-6, CCL2, CCL5, IL-8), whereas 48 hour-treatment elevated the expression of anti-inflammatory factors (IL-10 and IL-6). LPS led to cell injury resulting from exaggerated cell apoptosis and necrosis. Finally, LPS inhibited small conductance Ca
-activated K
channel currents, enhanced Na
/Ca
-exchanger currents, prolonged action potential duration, suggesting cellular electrical dysfunctions. Our data demonstrate that hiPSC-CMs possess the functional reaction system involved in endotoxin-induced inflammation and can model some bacterium-induced inflammatory responses in cardiac myocytes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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