Short-QT syndrome is an inherited disorder characterized by a short QT interval and an increased risk of sudden cardiac death. The clinical significance of a short QT interval observed in a randomly ...recorded ECG is not known. Therefore, we assessed the prevalence and prognostic significance of a short QT interval in a general population.
QT intervals were measured from the 12-lead ECGs of 10 822 randomly selected middle-aged subjects (5658 males, mean age 44+/-8.4 years) enrolled in a population study and followed up for 29+/-10 years. The end points were all-cause and cardiovascular mortality. In addition to Bazett's method (corrected QT interval, or QTc), the Fridericia (QTfc) and nomogram (QTnc) methods were used to correct the QT interval for heart rate. The cutoff values for short QT intervals were defined as 320 ms (very short) and 340 ms (short). The prevalence of QT interval <320 ms based on QTc, QTfc, and QTnc was 0.10%, 0.08%, and 0.06%, and the prevalence of QT interval <340 ms was 0.4%, 0.3%, and 0.3%, respectively. The majority of subjects with short QT intervals were males. All-cause or cardiovascular mortality did not differ between subjects with a very short or short QT interval and those with normal QT intervals (360 to 450 ms). There were no sudden cardiac deaths, aborted sudden cardiac deaths, or documented ventricular tachyarrhythmias among subjects with a QTfc <340 ms.
A short QT interval does not appear to indicate an increased risk for all-cause or cardiovascular mortality in middle-aged nonreferral, community-based individuals.
Aims To determine whether QRS duration predicts sudden cardiac death (SCD) in patients with left ventricular hypertrophy and treated hypertension. Methods and results Over 4.8 ± 0.9 years follow-up ...of 9193 hypertensive patients with electrocardiographic evidence of LVH who were treated with atenolol- or losartan-based regimens, 178 patients (1.9%) suffered SCD. In multivariable analysis including randomized treatment, changing blood pressure over time, and baseline differences between patients with and without SCD, QRS duration was independently predictive of SCD (HR per 10 ms increase = 1.22, P < 0.001). Baseline QRS duration remained a significant predictor of SCD even after controlling for the presence or absence of left bundle branch block (HR = 1.17, P = 0.001) and for changes in ECG LVH severity over the course of the study (HR = 1.16, P = 0.017). Conclusion In the setting of aggressive antihypertensive therapy, prolonged QRS duration identifies hypertensive patients at higher risk for SCD, even after controlling for left bundle branch block, other known risk factors for SCD, and changes in blood pressure and severity of left ventricular hypertrophy.
Aims
Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and ...sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive.
Methods and results
We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2328S, Q4201R, and V4653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 µg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2328S and V4653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca2+ release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca2+ release events as Ca2+ sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca2+ release events at lower concentrations of cAMP than cells transfected with wild-type RyR2.
Conclusion
CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca2+ waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT.
ABSTRACT—Left ventricular hypertrophy is a risk factor for cardiovascular mortality, including sudden cardiac death. Experimentally, left ventricular hypertrophy delays ventricular conduction and ...prolongs action potential duration. Electrocardiographic QRS duration and QT interval measures reflect these changes, but whether these measures can further stratify risk in patients with electrocardiographic left ventricular hypertrophy is unknown. We measured the QRS duration and QT intervals from the baseline 12-lead electrocardiograms in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, which included hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy randomized to either losartan-based or atenolol-based treatment to lower blood pressure. In the present study, we related study baseline electrocardiographic measures to cardiovascular and all-cause mortality. There were 5429 patients (male 45.8%; mean age 66±7 years) included in the present analyses. After a mean follow-up of 4.9±0.8 years, there were 417 deaths from all causes, including 214 cardiovascular deaths. In separate univariate Cox regression analyses, QRS duration and several QT measures were significant predictors of cardiovascular mortality and all-cause mortality. However, in multivariate Cox analyses including all electrocardiographic measures and adjusting for other risk factors as well as treatment strategy, only QRS duration and maximum rate-adjusted QTapex interval remained as significant independent predictors of cardiovascular (P =0.022 and P =0.037, respectively) and all-cause mortality (P =0.038 and P =0.002, respectively). In conclusion, in a hypertensive risk population identified by electrocardiographic left ventricular hypertrophy, increased QRS duration and maximum QTapex interval can further stratify mortality risk even in the setting of effective blood pressure-lowering treatment.
Climate change has multiple effects on Baltic Sea species, communities and ecosystem functioning through changes in physical and biogeochemical environmental characteristics of the sea. Associated ...indirect and secondary effects on species interactions, trophic dynamics and ecosystem function are expected to be significant. We review studies investigating species-, population- and ecosystem-level effects of abiotic factors that may change due to global climate change, such as temperature, salinity, oxygen, pH, nutrient levels, and the more indirect biogeochemical and food web processes, primarily based on peer-reviewed literature published since 2010.
The ECG strain pattern of ST depression and T-wave inversion is strongly associated with left ventricular hypertrophy (LVH) independently of coronary heart disease and with an increased risk of ...cardiovascular morbidity and mortality in hypertensive patients. However, whether ECG strain is an independent predictor of new-onset congestive heart failure (CHF) in the setting of aggressive antihypertensive therapy in unclear.
The relationship of ECG strain at study baseline to the development of CHF was examined in 8696 patients with no history of CHF who were enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. All patients had ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria on a screening ECG, were treated in a blinded manner with atenolol- or losartan-based regimens, and were followed up for a mean of 4.7+/-1.1 years. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite the QRS axis in lead V5 or V6. ECG strain was present in 923 patients (10.6%), and new-onset CHF occurred in 265 patients (3.0%), 26 of whom had a CHF-related death. Compared with patients who did not develop CHF, hypertensive patients who developed CHF were older; were more likely to be black, current smokers, and diabetic; were more like to have a history of myocardial infarction, ischemic heart disease, stroke, or peripheral vascular disease; and had greater baseline severity of LVH by Cornell product and Sokolow-Lyon voltage, higher baseline body mass indexes, higher serum glucose levels and albuminuria, similar baseline systolic and diastolic pressures, and reductions in diastolic pressure with treatment but greater reductions in systolic pressure. In univariate Cox analyses, ECG strain was a significant predictor of new-onset CHF (hazard ratio HR, 3.27; 95% CI, 2.49 to 4.29) and CHF mortality (HR, 4.74; 95% CI, 2.11 to 10.64). In Cox multivariable analyses adjusting for baseline differences between patients with and without new-onset CHF, in-treatment differences in systolic and diastolic pressures, Sokolow-Lyon voltage, and Cornell product, and the impact of treatment with losartan versus atenolol on outcomes, ECG strain remained a significant predictor of incident CHF (HR, 1.80; 95% CI, 1.30 to 2.48) and CHF-related death (HR, 2.78; 95% CI, 1.02 to 7.63).
ECG strain identifies hypertensive patients at increased risk of developing CHF and dying as a result of CHF, even in the setting of aggressive blood pressure lowering.
The ECG strain pattern of lateral ST depression and T-wave inversion is a marker for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, whether ECG strain is an ...independent predictor of cardiovascular (CV) morbidity and mortality in the setting of aggressive antihypertensive therapy is unclear. ECGs were examined at study baseline in 8854 hypertensive patients with ECG LVH who were treated in a blinded manner with atenolol- or losartan-based regimens. Strain was defined by the presence of a downsloping convex ST segment with an inverted asymmetrical T wave opposite to the QRS axis in leads V5 and/or V6 and was present in 971 patients (11.0%). The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study composite end point of CV death or nonfatal myocardial infarction or stroke occurred in 1035 patients (11.7%). In Cox analyses adjusting only for treatment effect, ECG strain was a significant predictor of CV death (hazard ratio HR 2.26, 95% confidence interval CI 1.78 to 2.86), fatal/nonfatal myocardial infarction (HR 2.16, 95% CI 1.67 to 2.80), fatal/nonfatal stroke (HR 1.76, 95% CI 1.39 to 2.21), and the composite CV end point (HR 1.99, 95% CI 1.70 to 2.33). After further adjusting for standard CV risk factors, baseline blood pressure, and severity of ECG LVH, ECG strain remained a significant predictor of CV mortality (HR 1.53, 95% CI 1.18 to 2.00), myocardial infarction (HR 1.55, 95% CI 1.16 to 2.06), and the composite CV end point (HR 1.33, 95% CI 1.11 to 1.59). Thus, ECG strain is a marker of increased CV risk in hypertensive patients in the setting of aggressive blood pressure lowering, independent of baseline severity of ECG LVH.
Introduction Regular physical exercise reduces cardiovascular morbidity. 1 2 However, our clinical impression is that atrial fibrillation is quite common in otherwise healthy middle aged men engaged ...in long term vigorous endurance sports. Comment Vigorous long term exercise is associated with atrial fibrillation in healthy middle aged men despite protecting against coronary heart disease and premature death.
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Objectives. QT interval prolongation is associated with increased risk of sudden cardiac death at the population level. As 30–40% of the QT‐interval variability is heritable, we tested the ...association of common LQTS and NOS1AP gene variants with QT interval in a Finnish population‐based sample.
Methods. We genotyped 12 common LQTS and NOS1AP genetic variants in Health 2000, an epidemiological sample of 5043 Finnish individuals, using Sequenom MALDI‐TOF mass spectrometry. ECG parameters were measured from digital 12‐lead ECGs and QT intervals were adjusted for age, gender and heart rate with a nomogram (Nc) method derived from the present study population.
Results. The KCNE1 D85N minor allele (frequency 1.4%) was associated with a 10.5 ms (SE 1.6) or 0.57 SD prolongation of the adjusted QTNc interval (P = 3.6 × 10−11) in gender‐pooled analysis. In agreement with previous studies, we replicated the association with QTNc interval with minor alleles of KCNH2 intronic SNP rs3807375 1.6 ms (SE 0.4) or 0.08 SD, P = 4.7 × 10−5, KCNH2 K897T −2.6 ms (SE 0.5) or −0.14 SD, P = 2.1 × 10−7 and NOSA1P variants including rs2880058 4.0 ms (SE 0.4) or 0.22 SD, P = 3.2 × 10−24 under additive models.
Conclusions. We demonstrate that each additional copy of the KCNE1 D85N minor allele is associated with a considerable 10.5 ms prolongation of the age‐, gender‐ and heart rate‐adjusted QT interval and could thus modulate repolarization‐related arrhythmia susceptibility at the population level. In addition, we robustly confirm the previous findings that three independent KCNH2 and NOSA1P variants are associated with adjusted QT interval.
The global demand for renewable energy is on the rise. Expansion of onshore wind energy is in many parts of the world limited by societal acceptance, and also ecological impacts are a concern. Here, ...pragmatic methods are developed for the integration of high-dimensional spatial data in offshore wind energy planning. Over 150 spatial data layers are created, which either oppose or support offshore wind energy development, and represent ecological, societal, and economic factors. The method is tested in Finland, where interest in developing offshore wind energy is growing.
Analyses were done using a spatial prioritization approach, originally developed for the prioritization of high-dimensional ecological data, and rarely used in planning offshore wind energy. When all criteria are integrated, it is possible to find a balanced solution where offshore wind farms cause little disturbance to biodiversity and society, while at the same time yielding high profitability for wind energy production. Earlier proposed areas for offshore wind farms were also evaluated. They were generally well suited for wind power, with the exception of a couple of areas with comparatively high environmental impacts.
As an outcome, new areas well suited for large scale wind power deployment were recognized, where construction costs would be moderate and disturbance to biodiversity, marine industries and people limited. A novel tradeoff visualization method was also developed for the conflicts and synergies of offshore energy deployment, which could ease the dialogue between different stakeholders in a spatial planning context.
Overall, this study provides a generic and transparent approach for well-informed analysis of offshore wind energy development potential when conflict resolution between biodiversity, societal factors and economic profits is needed. The proposed approach is replicable elsewhere in the world. It is also structurally suitable for the planning of impact avoidance and conflict resolution in the context of other forms of construction or resource extraction.
•A novel approach was developed for the identification of areas suitable for offshore wind farms.•The approach resolves conflicts between economic, ecological and societal factors.•Disturbance to nature and people were minimized in the design of offshore wind farms.•The approach is applicable to high dimensional, high-resolution, spatial data.•The approach can be used elsewhere for similar applications of ecological impact avoidance.
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