Fragmented QRS is associated with ventricular arrhythmias in heart failure patients: a systematic review and meta-analysis

Introduction: Many primary prevention heart failure (HF) patients with an implantable cardiac defibrillator (ICD) rarely experience life-threatening ventricular arrhythmias (VA). New strategies are required to identify patients most at risk of VA and sudden cardiac death who would benefit from an ICD. One potential method is the detection of fragmented QRS (fQRS) on the electrocardiogram. The aim was to assess the predictive capacity of fQRS for VA and mortality in ischemic (ICM) and non-ischemic cardiomyopathy (NICM) primary prevention HF patients. Methods and Results: A systematic review and meta-analysis of studies examining fQRS in HF patients with or without an ICD who met primary prevention indications with reduced ejection fraction ≤40%. Outcome measures were VA (or appropriate ICD therapy) and all-cause mortality. Ten studies involving 3885 patients were included for analysis. Most patients were male with non-fQRS patients being significantly younger (−1.5[−2.66, −0.42], p = .03). Diabetes was more likely in fQRS patients (1.12[1.01, 1.25], p = .03) while non-fQRS patients were 28% more likely to have a history of atrial fibrillation (0.82[0.67,1.00], p = .05). Ventricular arrhythmias were significantly 1.5 times more likely in patients with fQRS (1.51[1.02, 2.25], p = .04). HF patients were 1.7 times more likely to die of any cause if fQRS was present (1.68[1.13, 2.52], p = .01). NICM patients with fQRS have a significant 2.6-fold increased incidence of death compared with ICM patients (2.55[1.63, 3.98], p < .0001). Conclusion: fQRS is associated with VA and all-cause mortality and may be a novel marker in the risk stratification of primary prevention HF patients indicated for ICD implantation

Primary prevention implantable cardiac defibrillators: a Townsville district perspective

Background: Despite major advances in treating patients with severe heart failure, deciding who should receive an implantable cardiac defibrillator (ICD) remains challenging. Objective: To study the risk factors and mortality in patients after receiving an ICD (January 2008–December 2015) in a regional hospital in Australia. Methods: Eighty-two primary prevention patients received an ICD for ischemic cardiomyopathy (ICM, n = 41) and non-ischemic cardiomyopathy (NICM, n = 40) with 4.8-yrs follow-up. One patient had mixed ICM/NICM indications. Ventricular arrhythmias were assessed using intracardiac electrograms. Statistical analysis compared the total population and ICM and NICM groups using Kaplan-Meier for survival, Cox regression for mortality predictors, and binary logistic regression for predictors of ventricular arrhythmias (p < 0.05). Results: Major risk factors were hypercholesterolemia (70.7%), hypertension (47.6%), and obesity (41.5%). Severe obstructive sleep apnea (OSA) was found exclusively in NICM patients (23.7%, p = 0.001). Mortality was 30.5% after 4.8-yrs. The majority of patients (n=67) had no sustained ventricular arrhythmias yet 28% received therapy (n = 23), 18.51% were appropriate (n = 15), and 13.9% inappropriate (n = 11). Patients receiving ≥2 incidences of inappropriate shocks were 18-times more likely to die (p =0.013). Three sudden cardiac deaths (SCD) (3.7%) were prevented by the ICD. Conclusion: Patients implanted with an ICD in Townsville had 30.5% all-cause mortality after 4.8-yrs. Only 28% of patients received ICD therapy and 13.9% were inappropriate. OSA may have contributed to the fourfold increase in inappropriate therapy in NICM patients. Our study raises important efficacy, ethical and healthcare cost questions about who should receive an ICD, and possible regional and urban center disparities

Predicting arrhythmias in primary prevention heart failure patients: picking up the fragments

Identifying patients with high-risk heart failure (HF) who would benefit from an implantable cardioverter-defibrillator (ICD) remains controversial. A potential marker for arrhythmic sudden death is fragmented QRS (fQRS). fQRS is the notching and slurring of the QRS complex in a 12-lead ECG and it indicates abnormal ventricular depolarisation and myocardial scarring and fibrosis. However, before fQRS complex can be included into selection criteria for ICD therapy, more complete reporting is required on their association with malignant arrhythmias, left ventricular remodelling and myocardial scarring/fibrosis in patients with HF. The molecular basis of the fQRS-arrhythmia-fibrosis connection in HF also needs to be explored. It is not widely appreciated that changes in the QRS complex and phases 0 and 1 of the ventricular action potential occur before contraction and predetermine Ca2+ release during contraction and later Ca2+ sparks. It is currently not known whether the different zig-zag patterns of the QRS are associated with aberrant Ca2+ cycling and arrhythmogenic sparks in patients with HF

Induction and repression of the sty operon in Pseudomonas putida CA-3 during growth on phenylacetic acid under organic and inorganic nutrient-limiting continuous culture conditions

The effects of various nutrient-limiting conditions on expression of the sty operon in Pseudomonas putida CA-3 were investigated. It was observed that limiting concentrations of the carbon source phenylacetic acid, resulted in high levels of phenylacetyl coenzyme A (CoA) ligase activity, this was accompanied also by upper pathway styrene monooxygenase enzyme activity. The introduction of inorganic nutrient limitations, (nitrate, sulfate and phosphate), caused a dramatic reduction in detectable levels of phenylacetyl CoA ligase activity, particularly in the presence of the primary carbon source, succinate. Under these conditions it was no longer possible to detect styrene monooxygenase activity. Reverse transcription PCR analysis of total RNA, isolated under each of the continuous culture conditions examined, revealed that variations in the levels of enzyme activity coincided with altered patterns of corresponding paaK (phenylacetyl CoA ligase) and styA (styrene monooxygenase) gene expression. Transcription of the upper pathway regulatory sensor kinase gene styS was also observed to be growth condition-dependent. These observations suggest that induction/repression of the sty operon in P. putida CA-3, during growth on phenylacetic acid under continuous culture conditions, involves regulatory mechanisms coordinately affecting both the upper and lower pathways and acting at the level of gene transcriptio

The imprint of strong-storm tracks on winter weather in North America

Northern Hemisphere winter storm tracks and their relation to winter weather are investigated using CFSR data. Storm tracks are described by isentropic PV maxima within a Lagrangian framework; these correspond well with those described in previous studies. Our diagnostics focus on strong-storm tracks, which are comprised of storms that achieve a maximum PV exceeding the mean value by one standard deviation. Large increases in diabatic heating related to deep convection occur where the storm tracks are most intense. The cyclogenesis pattern shows that strong storms generally develop on the upstream sectors of the tracks. Intensification happens towards the eastern North Pacific and all across the North Atlantic Ocean, where enhanced storm track-related weather is found. In this study, the relation of storm tracks to near-surface winds and precipitation is evaluated. The largest increases in storm track-related winds are found where strong storms tend to develop and intensify, while storm precipitation is enhanced in areas where the storm tracks have the highest intensity. Strong storms represent about 16% of all storms but contribute 30-50% of the storm precipitation in the storm track regions. Both strong-storm related winds and precipitation are prone to cause storm-related losses in the eastern US and North American coasts. Over the oceans, maritime operations are expected to be most vulnerable to damage offshore of the US coasts. Despite making up a small fraction of all storms, the strong-storm tracks have a significant imprint on winter weather in North America potentially leading to structural and economic loss

Regional Climate Trends and Scenarios for the U.S. National Climate Assessment Part 4. Climate of the U.S. Great Plains

This document is one of series of regional climate descriptions designed to provide input that can be used in the development of the National Climate Assessment (NCA). As part of a sustained assessment approach, it is intended that these documents will be updated as new and well-vetted model results are available and as new climate scenario needs become clear. It is also hoped that these documents (and associated data and resources) are of direct benefit to decision makers and communities seeking to use this information in developing adaptation plans. There are nine reports in this series, one each for eight regions defined by the NCA, and one for the contiguous U.S. The eight NCA regions are the Northeast, Southeast, Midwest, Great Plains, Northwest, Southwest, Alaska, and Hawai‘i/Pacific Islands. These documents include a description of the observed historical climate conditions for each region and a set of climate scenarios as plausible futures – these components are described in more detail below. While the datasets and simulations in these regional climate documents are not, by themselves, new, (they have been previously published in various sources), these documents represent a more complete and targeted synthesis of historical and plausible future climate conditions around the specific regions of the NCA. There are two components of these descriptions. One component is a description of the historical climate conditions in the region. The other component is a description of the climate conditions associated with two future pathways of greenhouse gas emissions

ACE-inhibitors and Angiotensin-2 Receptor Blockers are not associated with severe SARS-COVID19 infection in a multi-site UK acute Hospital Trust

Aims: The SARS‐CoV‐2 virus binds to the angiotensin‐converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID‐19 infection. Methods and results: We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID‐19 at two hospitals with a multi‐ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co‐morbidities, was 0.63 (95% confidence interval 0.47–0.84, P < 0.01). Conclusions: There was no evidence for increased severity of COVID‐19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta‐analyses and randomised clinical trials