Heart Failure with Preserved Ejection Fraction and Sudden Death: How to Identify High Risk Patients?

Background: Cardiac failure with preserved ejection fraction corresponds to half of the cardiac failure cases, having a similar prognosis to patients with reduced ejection fraction. Cardiac sudden death is responsible to about one quarter of the death on these patients. Despite some trials were intended to identify patients with a higher risk to these outcome, it is not already know: how we should proceed to stratify the risk of sudden death in this patients. Methods: To assess the profile of patients with cardiac sudden death and cardiac failure with preserved ejection fraction, we did a literature review, searching for the newer articles about the theme. Outcome: Several trials were published involving patients with divers characteristics that can help us to identify patients with a higher risk of sudden death. The publication of risk score demonstrated that would be possible to identify patients with a >10% risk of sudden death in 5 years, what would be equivalent to the risk of reduced ejection fraction patients eligible to implantable cardioverter-defibrillator (ICD) therapy. Trials with electrophysiological study and programmed ventricular stimulation showed a good strategy to identify low risk patients for future arrhythmic events. Conclusion: Sudden death must be a target of the therapy in the patients with preserved heart failure. Efforts should be done with the objective to identify higher risk patients and search for the better risk stratification strategy, and after that, the definition of the benefit or not, of the invasive therapy as ICD.

NOS1AP polymorphisms reduce NOS1 activity and interact with prolonged repolarization in arrhythmogenesis

Aims NOS1AP single-nucleotide polymorphisms (SNPs) correlate with QT prolongation and cardiac sudden death in patients affected by long QT syndrome type 1 (LQT1). NOS1AP targets NOS1 to intracellular effectors. We hypothesize that NOS1AP SNPs cause NOS1 dysfunction and this may converge with prolonged action-potential duration (APD) to facilitate arrhythmias. Here we test (i) the effects of NOS1 inhibition and their interaction with prolonged APD in a guinea pig cardiomyocyte (GP-CMs) LQT1 model; (ii) whether pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from LQT1 patients differing for NOS1AP variants and mutation penetrance display a phenotype compatible with NOS1 deficiency. Methods and results In GP-CMs, NOS1 was inhibited by S-Methyl-L-thiocitrulline acetate (SMTC) or Vinyl-L-NIO hydrochloride (L-VNIO); LQT1 was mimicked by IKs blockade (JNJ303) and β-adrenergic stimulation (isoproterenol). hiPSC-CMs were obtained from symptomatic (S) and asymptomatic (AS) KCNQ1-A341V carriers, harbouring the minor and major alleles of NOS1AP SNPs (rs16847548 and rs4657139), respectively. In GP-CMs, NOS1 inhibition prolonged APD, enhanced ICaL and INaL, slowed Ca2+ decay, and induced delayed afterdepolarizations. Under action-potential clamp, switching to shorter APD suppressed ‘transient inward current’ events induced by NOS1 inhibition and reduced cytosolic Ca2+. In S (vs. AS) hiPSC-CMs, APD was longer and ICaL larger; NOS1AP and NOS1 expression and co-localization were decreased. Conclusion The minor NOS1AP alleles are associated with NOS1 loss of function. The latter likely contributes to APD prolongation in LQT1 and converges with it to perturb Ca2+ handling. This establishes a mechanistic link between NOS1AP SNPs and aggravation of the arrhythmia phenotype in prolonged repolarization syndromes.

New possibilities of electrocardiography analysis for the diagnosis of myocardial ischemia

Aim - to investigate new possibilities of application of electrocardiography (ECG) for diagnostics of myocardial ischemia with the use of modern information technologies. Material and methods. The analyse of modern scientific sources, which were dedicated to the researches of the new uninvasion ECG-metods application was conducted. The new uninvasion ECG-metods reflect the electro-physiological processes in the different phases of the cardiac cycle and can have diagnostic meaningfulness for the detecting of early ischemic changes in myocardium. Results. The detection of the early stages of cardiovascular pathology is an important step for preventing complications and requires for the development of accessible, inexpensive and effective methods of diagnostics. Last years a lot of attention to the studyng of new uninvasion methods of diagnostics of early ischemic marcers and electric instability of myocardium with the use of information technologies processing of electrocardiogram has been paying. We investigated the different approaches of the deeper analysis of processing of ECG-signal and estimated the possibilities of the use of ECG method for diagnostics of myocardium ischemic changes and prognosis of cardiac sudden death, what are discussed in literature and proposed for using in the practiсe. Among them, electrocardiography of high-resolution with the estimation of late potentials of ventricles, determination micro and macro alternation of T-wave, heart rhytm variability and ECG that is conducted in phase space ECG-Images. Conclusion. The analys of results of reaserchers about of the processing of the new uninvasion ECG-metods with autometed information technology, which may reflect the electro-physiological processes in the different phases of the cardiac cycle, allows us to state that the using of them helps to get more information about the state of the cardiovascular system and early ischemic changes in myocardium.

Abstract 16193: Sport Activity and Sudden Cardiac Death in Women

Background: No specific data are available on the prevalence and characteristics of cardiac sudden death (SCD) during sport activities among young women. Methods and Results: From a prospective 30-year target project on SCD in the young, involving 695 subjects 1-40 years old who died suddenly in the same geographic areas, 649 were due to SCD (196 female, 30%). A total of 76 young adults were competitive athletes and died during or soon after effort (11%). Only 6 (8%) of such events occurred in women (mean age 23±10 yrs, range 12-38), specifically during jogging (2), and swimming, volley, gymnastic and triathlon (one each). Cause of death seemed more likely to be associated with structurally normal heart in women compared with men (50% versus 7%; P<0.01). In particular, while inherited cardiomyopathies (i.e. arrhythmogenic, hypertrophic and dilated) and coronary atherosclerosis are the leading cause in the overall population of athletes (24/76, 32% and 11/76, 14.5% respectively) and in the male sub-group (24/70, 34% and 11/70, 16%, respectively), they were never observed in female athletes. Conclusions: Sports-related SCD in women is dramatically less common compared with men. In the female athletic population, SCD occurs in the setting of a structurally normal heart in half of cases. In a country with obligatory pre-participation screening for sport activity, inherited cardiomyopathies and atherosclerotic coronary artery diseases are almost exclusive of the male athletic population.