Az oxidatív stressz szerepe az amiodarontoxicitásban, valamint a hypertoniás betegek balkamra-diszfunkciójában és a megorzött ejekciós frakciójú szívelégtelenségben

The author briefly summarizes his scientific work investigating the role of oxidative stress in cardiovascular disorders. Using in vitro biochemical, biophysical and in vivo animal research it was found that oxidative stress plays a substantial role in the pathogenesis of amiodarone toxicity and antioxidants co-administered with amiodarone exert at least partial protective effect on amiodarone toxicity, while antioxidants did not diminish and perhaps even enhanced the antiarrhythmic action of amiodarone. Thus, co-administration of antioxidants with amiodarone may lead to the more widespread application of amiodarone, which is currently the most potent available antiarrhythmic agent, but its clinical use is limited due the potentially severe toxic effect In hypertensive patients with normal ejection fraction, the most common precursor condition of heart failure with preserved ejection fraction, the potential primary causal role of oxidative stress and inflammation in the left ventricular systolic, diastolic and atrial dysfunction, which are important determinants of the transition of hypertensive heart disease to heart failure with preserved ejection fraction was verified

Novel electrocardiographic criteria may render possible the more accurate recognition of cardiac amyloidosis

The early diagnosis of cardiac amyloidosis (CA) is paramount, since there are effective therapies that improve patient survival. The diagnostic accuracy of classical electrocardiographic (ECG) signs, such as low voltage, pseudoinfarct pattern, and conduction disturbances in the diagnosis of CA, is inferior to that of the echocardiographic myocardial deformation criteria; therefore, our aim was to find more accurate novel ECG criteria for this purpose.We tested the diagnostic value of five novel ECG criteria, two of them devised by us, in 34 patients with confirmed CA (20 transthyretin amyloidosis and 14 AL amyloidosis) and 45 control patients with left ventricular hypertrophy on echocardiography due to hypertension, valvular aortic stenosis and hypertrophic cardiomyopathy. The following novel ECG criteria, that suggested CA, were tested: QRS amplitude in lead I 4.1 (TA: 77%, SE: 93%, SP: 38%, PPV: 79%, NPV: 69%, AUC: 0.65) echocardiographic criteria. Among the classical criteria, the low voltage in limb leads criterion was present most frequently (in 73.5%) in patients with CA, with slightly worse diagnostic value than the novel ECG criteria (TA: 78.5%, SE: 73.5%, SP: 82.2%, PPV: 75.8%, NPV: 80.4%).The novel ECG criteria [mostly the aVR < 0.5, (I + aVR)/(V1-4 ) < 0.375] seem at least as reliable in the diagnosis of CA as the best echocardiographic myocardial deformation criteria and might be used either together with the echocardiographic criteria or as stand-alone criteria to diagnose CA in the future

Inflammation and oxidative stress caused by nitric oxide synthase uncoupling might lead to left ventricular diastolic and systolic dysfunction in patients with hypertension

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Vereckei criteria as a diagnostic tool amongst emergency medicine residents to distinguish between ventricular tachycardia and supra-ventricular tachycardia with aberrancy

SummaryBackgroundAccurate electrocardiographic (ECG) differentiation of ventricular tachycardia (VT) from supraventricular tachycardia with aberrancy (SVT-A) on ECG is key to therapeutic decision-making in the emergency department (ED) setting.ObjectiveThe goal of this study was to test the accuracy and agreement of emergency medicine residents to differentiate VT from SVT-A using the Vereckei criteria.MethodsSix emergency medicine residents volunteered to participate in the review of 114 ECGs from 86 patients with a diagnosis of either VT or SVT-A based on an electrophysiology study. The resident reviewers initially read 12-lead ECGs blinded to clinical information, and then one week later reviewed a subset of the same 12-lead ECGs unblinded to clinical information.ResultsOne reviewer was excluded for failing to follow study protocol and one reviewer was excluded for reviewing less than 50 blinded ECGs. The remaining four reviewers each read 114 common ECGs blinded to clinical data and their diagnostic accuracy for VT was 74% (sensitivity 70%, specificity 80%), 75% (sensitivity 76%, specificity 73%), 61% (sensitivity 81%, specificity 25%), and 68% (sensitivity 84%, specificity 40%). The intraclass correlation coefficient (ICC) was 0.31 (95% CI 0.22–0.42). Eliminating two of the four reviewers who left a disproportionately high number of ECGs unclassified resulted in an increase in overall mean diagnostic accuracy (70–74%) and agreement (0.31–0.50) in the two remaining reviewers. Three reviewers read 45 common ECGs unblinded to clinical information and had accuracies for VT 93%, 93% and 78%.ConclusionThe new single lead Vereckei criteria, when applied by emergency medicine residents achieved only fair-to-good individual accuracy and moderate agreement. The addition of clinical information resulted in substantial improvement in test characteristics. Further improvements (accuracy and simplification) of algorithms for differentiating VT from SVT-A would be helpful prior to clinical implementation

The mechanism of reduced longitudinal left ventricular systolic function in hypertensive patients with normal ejection fraction

Background: MacIver and Townsend’s hypothesis predicts, based on a mathematical model of left ventricular (LV) contraction, that preserved absolute radial wall thickening (radWT) due to LV hypertrophy is responsible for the normal ejection fraction (EF) in patients with heart failure with preserved ejection fraction (HFPEF). Methods: We tested the validity of this hypothesis by detailed echocardiography including evaluation of ventricular myocardial strain (S) using speckle tracking imaging in >60-year-old 18 controls and 94 hypertensive patients with normal EF. Results: Echocardiography revealed no LV diastolic dysfunction in 38/94(40%) patients with HT (HTDD- group), and 56/94(60%) patients had diastolic dysfunction (HTDD+ group). The absolute values of global longitudinal LV peak systolic S were significantly reduced in both patient groups (p<0.05 for HTDD-, p<0.01 for HTDD+ groups) versus the controls. There were no significant between-groups differences in circumferential and radial peak LV systolic Ss, radWT and EF. LV mass (LVM) (p<0.001), LVM/body mass index (BMI) (p<0.01) increased in the HTDD+ group and EF/LVM/BMI decreased in both patient groups (p<0.01 for HTDD-, p<0.001 for HTDD+ groups) versus the controls. LVM increased, EF/LVM/BMI decreased in the HTDD+ group versus the HTDD- group (p<0.05 and p<0.01 respectively). Conclusions: We demonstrated decreased longitudinal LV systolic function, and showed that preserved EF was due to preserved absolute radWT and not to increased radial or circumferential systolic function in patients with HT and normal EF, a potential HFPEF precursor condition. Instead of EF, rather EF/LVM/BMI might be used to detect subtle LV systolic dysfunction in hypertension and HFPEF

Genetic predisposition in patients with hypertension and normal ejection fraction to oxidative stress

The role of oxidative stress (OXS) due to myocardial nitric oxide synthase (NOS) uncoupling related to oxidative depletion of its cofactor tetrahydrobiopterin (BH4) emerged in the pathogenesis of heart failure with preserved ejection fraction (HFPEF). We determined the prevalence of 6 single nucleotide polymorphisms (SNPs) of genes encoding enzymes related to OXS, BH4 metabolism and NOS function in >60-year-old 94 patients with hypertension and 18 age-matched controls with normal EF. Using echocardiography 56/94(60%) patients with hypertension had left ventricular (LV) diastolic dysfunction (HTDD+ group), 38/94(40%) patients had normal LV diastolic function (HTDD- group). Four SNPs (rs841, rs3783641, rs10483639, rs807267) of guanosine triphosphate cyclohydrolase-1, the rate limiting enzyme in BH4 synthesis, 1 (rs4880) of manganese superoxide dismutase, and 1 (rs1799983) of endothelial NOS genes were genotyped using real time PCR method and Taqman probes. Protein carbonylation (PC), BH4 and total biopterin levels were measured from plasma samples. No between-groups difference in minor allele frequency (MAF) of SNPs was found. We calculated a genetic score indicating risk for OXS based on the MAFs of the SNPs. A high genetic risk for OXS was significantly associated with HTDD+ even after adjustment for confounding variables [OR(95%CI):4.79(1.12-20.54); p=0.035]. In both patient groups PC (p<0.05 for both), plasma BH4 (p<0.01 for both) and in the HTDD+ group total biopterin (p<0.05) increased vs. controls. In conclusion, in patients with hypertension and normal EF, a potential precursor of HFPEF, a partly genetically determined increased OXS seems to be associated with the presence of LV diastolic dysfunction