Clinical aspects of the three major genetic forms of long QT syndrome (LQT1, LQT2, LQT3)

Background

A comprehensive report on the clinical course of the three major genotypes of the long QT syndrome (LQTS) in a large U.S. patient cohort is lacking.

Methods

Our study consisted of 1,923 U.S. subjects from the Rochester‐based LQTS Registry with genotype‐positive LQT1 (n = 879), LQT2 (n = 807), and LQT3 (n = 237). We evaluated the risk of a first cardiac event (syncope, aborted cardiac arrest, or sudden cardiac death, whichever occurred first) from birth through age 50 years. Cox proportional hazards regression models incorporating clinical covariates were used to assess genotype‐specific risk of cardiac events.

Results

For all three genotypes, the cumulative probability of a first cardiac event increased most markedly during adolescence. Multivariate analysis identified proband status and QTc > 500 ms as predictors of cardiac events in all three genotypes, and males <14 years and females >14 years as predictors of cardiac events in LQT1 and LQT2 only. Beta‐blockers significantly reduced the risk of cardiac events in LQT1 (HR: 0.49, p = .002) and LQT2 patients (HR: 0.48, p = .001). A trend toward beta‐blocker benefit in reducing cardiac events was found in LQT3 females (HR: 0.32, p = .078), but not in LQT3 males (HR: 1.37, p = .611).

Conclusion

Risk factors and outcomes in LQTS patients varied by genotype. In all three genotypes, proband status and prolonged QTc were risk factors for cardiac events. Younger males and older females experienced increased risk in LQT1 and LQT2 only. Beta‐blockers were most effective in reducing cardiac events in LQT1 and LQT2, with a potential benefit in LQT3 females.

     

QT dispersion and myocardial viability in patients after acute myocardial infarction

BACKGROUND: In recent years QT dispersion (QTd) in post-infarct patients was estimated in many studies, but still little is known about its association with the presence of dysfunctional but viable myocardium. AIM: We investigated the relation between dispersion of QT interval and myocardial viability in patients after acute myocardial infarction (AMI). MATERIAL AND METHODS: In 52 patients (mean age 67.2+/-11.7) treated thrombolytically because of AMI 12-lead ECG and low dose-high dose dobutamine echocardiography was performed on 14th day after treatment. QTd and regional myocardial contractility were estimated three times: at baseline, low dose dobutamine (LDD) (10-15 microg/kg per min) and high dose dobutamine (HDD) infusion (up to 40 microg/kg per min). RESULTS: Patients with viable myocardium had lower baseline QTd than patients with only necrosis in infarct zone. Significant increase in QTd was shown during LDD and HDD both in patients with and without myocardial viability. During infusion of HDD QTd was significantly higher in patients with myocardial ischemia. The greatest percentage increase of QTd at HDD was shown in patients with biphasic response to dobutamine infusion i.e. with myocardial viability evidenced at LDD and myocardial ischemia at HDD. CONCLUSION: Patients with preserved myocardial viability had lower QTd values compared to those with similar left ventricular dysfunction but caused only by post-infarction necrosis. Ischemia evoked on 14th day after AMI was accompanied by greater increase in QTd in patients with myocardial viability in infarct region than in patients without. It may be one of the reasons of greater risk of serious ventricular arrhythmias in such patients during myocardial ischemia.     

Attempt to eliminate health inequalities in Poland arising at the time of political and economic transformation: Polish 400 Cities Project.

AIM: Epidemiological data show that citizens of small towns and villages have presented worse trends in cardiovascular mortality during the political, social and economic transformation in Poland during past 15 years than citizens of large towns. To try to eliminate these inequalities the Polish 400 Cities Project (P400CP), a large educational and interventional project, was prepared. The project consists of two arms: medical and social interventions. MATERIAL AND METHODS: The main aim of the medical screening intervention in P400CP is to increase detection and control of cardiovascular risk factors in inhabitants of 418 small cities (<8000 inhabitants) and surrounding villages, particularly in men and people of lower education. In 2003 and 2004 the P400CP covered 123 cities. All together, 36 696 subjects aged between 18 and 98 years were examined. In all participants, blood pressure (BP), anthropometric measurements, laboratory tests and questionnaire interviews were performed. The social arm of P400CP is one of multi-level educational intervention. Modern techniques of social psychology and marketing were involved to increase participation in interventions. RESULTS: Only 12.5% of all subjects had normal BP, cholesterol (<190 mg/dl) and glucose (<100 mg/dl in whole capillary blood) levels. During the first screening visit 65.5% of all examined subjects had BP>/=140 mmHg or >/=90 mmHg. The fasting glucose level was increased in 19% of women and 26% of men. Almost two-third of all subjects had a total cholesterol level above the norm. CONCLUSIONS: The prevalence of cardiovascular risk factors in participants of the screening programme P400CP in small towns in Poland was very high. High prevalence and low control of risk factors in participants of the P400CP confirm the decision to target this programme at citizens of small towns and villages.     

Association of the ScaI atrial natriuretic peptide gene polymorphism with nonfatal myocardial infarction and extent of coronary artery disease

Background There is growing evidence from recent studies that atrial natriuretic peptide (ANP) plays an important part in coronary blood flow regulation and in atherosclerosis. Transition T2238→C in the atrial natriuretic peptide (ANP) precursor gene, which leads potentially to the translation of ANP with 2 additional arginines, has been suggested to be associated with salt-sensitive hypertension. According to our knowledge, this study is the first to look for the potential association of the ScaI ANP gene polymorphism with the history of nonfatal myocardial infarction and the extent of coronary artery disease (CAD).Methods The study was performed in 847 consecutive, white patients (719 men and 128 women) with significant coronary artery stenosis confirmed by means of elective coronary angiography (at least 1 coronary artery with ≥50% lumen narrowing). Screening for the T2238→C substitution was performed by means of polymerase chain reaction of genomic DNA, followed by ScaI digestion and agarose gel electrophoresis.Results We found a significant association of the A2A2 ScaI ANP genotype with a higher incidence of positive history of nonfatal myocardial infarction (odds ratio 1.85, 95% CI 1.33-2.58) and multiple-vessel CAD (odds ratio 1.45, 95% CI 1.02-2.06). The ScaI ANP genotype distribution did not differ with age, sex, body mass index, plasma lipids, hypertension, diabetes mellitus, and family history of CAD in studied groups.Conclusions Our results suggest that the ScaI ANP polymorphism may be associated with nonfatal myocardial infarction and the extent of CAD. However, the precise mechanism of this association remains to be determined. (Am Heart J 2003;145:125-31.)     

Role of kinin B2 receptor signaling in the recruitment of circulating progenitor cells with neovascularization potential

Reduced migratory function of circulating angiogenic progenitor cells (CPCs) has been associated with impaired neovascularization in patients with cardiovascular disease (CVD). Previous findings underline the role of the kallikrein-kinin system in angiogenesis. We now demonstrate the involvement of the kinin B2 receptor (B(2)R) in the recruitment of CPCs to sites of ischemia and in their proangiogenic action. In healthy subjects, B(2)R was abundantly present on CD133(+) and CD34(+) CPCs as well as cultured endothelial progenitor cells (EPCs) derived from blood mononuclear cells (MNCs), whereas kinin B1 receptor expression was barely detectable. In transwell migration assays, bradykinin (BK) exerts a potent chemoattractant activity on CD133(+) and CD34(+) CPCs and EPCs via a B(2)R/phosphoinositide 3-kinase/eNOS-mediated mechanism. Migration toward BK was able to attract an MNC subpopulation enriched in CPCs with in vitro proangiogenic activity, as assessed by Matrigel assay. CPCs from cardiovascular disease patients showed low B(2)R levels and decreased migratory capacity toward BK. When injected systemically into wild-type mice with unilateral limb ischemia, bone marrow MNCs from syngenic B(2)R-deficient mice resulted in reduced homing of sca-1(+) and cKit(+)flk1(+) progenitors to ischemic muscles, impaired reparative neovascularization, and delayed perfusion recovery as compared with wild-type MNCs. Similarly, blockade of the B(2)R by systemic administration of icatibant prevented the beneficial effect of bone marrow MNC transplantation. BK-induced migration represents a novel mechanism mediating homing of circulating angiogenic progenitors. Reduction of BK sensitivity in progenitor cells from cardiovascular disease patients might contribute to impaired neovascularization after ischemic complications.     

A counterpoint paper: Comments on the electrocardiographic part of the 2018 Fourth Universal Definition of Myocardial Infarction endorsed by the International Society of Electrocardiology and the International Society for Holter and Noninvasive Electrocardiology

The Fourth Universal Definition of Myocardial Infarction (FUDMI) focuses on the distinction between nonischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI, and the ECG is the main available tool for (a) detecting acute ischemia, (b) triage, and (c) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI.     

Assessment of the Impact of Shot-Peening on the Fatigue Life of a Compressor Blade Subjected to Resonance Vibrations

This publication presents an assessment of the influence of a surface treatment such as shot-peening on the fatigue life of a compressor blade exposed to resonant vibrations. As part of the work, a geometric model of the blade was developed, and a numerical modal and fatigue analysis were performed. The fatigue analysis was based on the Manson–Coffin–Basquin and Ramberg–Osgood models. Additionally, the location of the highest equivalent stresses was established. Based on the results of the strength analysis, two points were identified where a fatigue crack may potentially occur. As part of the work, the influence of different values of residual stresses on the results of the fatigue life was determined. The obtained results were compared to the literature values of fatigue life for this blade. A secondary objective of the study was to determine the size of the grains at various points of the blade, as well as the thickness of the layer plasticized as a result of peening. The relationship between the location of the highest values of the equivalent stresses and the thickness of the plasticized layer was determined. An explanation of the effect of shot-peening on the increase in the fatigue life of the blade was proposed.