Spatial and temporal trends and risk factors for intentional carbon monoxide poisoning hospitalizations in England between 2002 and 2016.

INTRODUCTION: Suicide and mental health disorders are a recognized increasing public concern. Most suicide prevention rely on evidence from mortality data, although suicide attempts are a better predictor for completed suicides. Understanding spatio-temporal patterns and demographic profiles of people at risk can improve suicide prevention schemes, including for carbon monoxide (CO) poisoning, a common method for gas-related suicides. OBJECTIVE: Describe spatio-temporal patterns of intentional CO poisoning hospitalization rates in England between 2002 and 2016, and identify population sub-groups at risk. METHODS: We used NHS Digital's Hospital Episode Statistics (HES) routinely collected data on hospital admissions for intentional CO poisoning. We estimated age-standardised rates (ASR) by year, gender and residential small-area characteristics, including rural/urban, deprivation and ethnic composition. Temporal trends were assessed through linear regression and joinpoint regression analysis. Regional differences were explored. RESULTS: On average, we identified 178 hospital admissions for intentional CO poisoning per year. The ASR decreased substantially over the study period, particularly among males (average annual percent change of -7.8 % (95 % CI: -11.0; -4.6)), in comparison to 3.9 % (95%CI, -6.4; -1.4) among females. Most admissions (81 %) occurred in males. White men aged 35-44 years were particularly at risk. The ASR in London (0.08/100,000) was almost six times lower than in the South-West (0.47/100,000). CONCLUSIONS: This study provides novel insights into attempted suicides by intentional CO poisoning. Further prevention interventions, targeting sub-groups at risk (i.e. white men in their 30s/40s), need to be developed and implemented to reduce the burden of suicides and of CO poisoning.

Trends in Temperature-associated Mortality in São Paulo (Brazil) between 2000 and 2018: an Example of Disparities in Adaptation to Cold and Heat.

Exposure to non-optimal temperatures remains the single most deathful direct climate change impact to health. The risk varies based on the adaptation capacity of the exposed population which can be driven by climatic and/or non-climatic factors subject to fluctuations over time. We investigated temporal changes in the exposure-response relationship between daily mean temperature and mortality by cause of death, sex, age, and ethnicity in the megacity of São Paulo, Brazil (2000-2018). We fitted a quasi-Poisson regression model with time-varying distributed-lag non-linear model (tv-DLNM) to obtain annual estimates. We used two indicators of adaptation: trends in the annual minimum mortality temperature (MMT), i.e., temperature at which the mortality rate is the lowest, and in the cumulative relative risk (cRR) associated with extreme cold and heat. Finally, we evaluated their association with annual mean temperature and annual extreme cold and heat, respectively to assess the role of climatic and non-climatic drivers. In total, we investigated 4,471,000 deaths from non-external causes. We found significant temporal trends for both the MMT and cRR indicators. The former was decoupled from changes in AMT, whereas the latter showed some degree of alignment with extreme heat and cold, suggesting the role of both climatic and non-climatic adaptation drivers. Finally, changes in MMT and cRR varied substantially by sex, age, and ethnicity, exposing disparities in the adaptation capacity of these population groups. Our findings support the need for group-specific interventions and regular monitoring of the health risk to non-optimal temperatures to inform urban public health policies.

Risk of cardiovascular mortality, stroke and coronary heart mortality associated with aircraft noise around Congonhas airport, São Paulo, Brazil: a small-area study.

BACKGROUND: Noise pollution is increasingly recognised as a public health hazard, yet limited evidence is available from low- and middle-income countries (LMIC), particularly for specific sources. Here, we investigated the association between day-night average (Ldn) aircraft noise and the risk of death due to cardiovascular disease (CVD), stroke and coronary heart disease (CHD) at small-area level around São Paulo's Congonhas airport, Brazil during the period 2011-2016. METHODS: We selected 3259 census tracts across 16 districts partially or entirely exposed to ≥50 dB aircraft noise levels around the Congonhas airport, using pre-modelled 5 dB Ldn noise  bands (≤50 dB to > 65 dB). We estimated the average noise exposure per census tract using area-weighting. Age, sex and calendar year-specific death counts for CVD, stroke and CHD were calculated by census tract, according to the residential address at time of death. We fitted Poisson regression models to quantify the risk associated with aircraft noise exposure, adjusting for age, sex, calendar year and area-level covariates including socioeconomic development, ethnicity, smoking and road traffic related noise and air pollution. RESULTS: After accounting for all covariates, areas exposed to the highest levels of noise (> 65 dB) showed a relative risk (RR) for CVD and CHD of 1.06 (95% CI: 0.94; 1.20) and 1.11 (95%CI: 0.96; 1.27), respectively, compared to those exposed to reference noise levels (≤50 dB). The RR for stroke ranged between 1.05 (95%CI: 0.95;1.16) and 0.91 (95%CI: 0.78;1.11) for all the noise levels assessed. We found a statistically significant positive trend for CVD and CHD mortality risk with increasing levels of noise (p = 0.043 and p = 0.005, respectively). No significant linear trend was found for stroke. Risk estimates were generally higher after excluding road traffic density, suggesting that road traffic air and noise pollution are potentially important confounders. CONCLUSIONS: This study provides some evidence that aircraft noise is associated with increased risk of CVD and CHD mortality in a middle-income setting. More research is needed to validate these results in other LMIC settings and to further explore the influence of residual confounding and ecological bias. Remarkably, 60% of the study population living near the Congonhas airport (~ 1.5 million) were exposed to aircraft noise levels > 50 dB, well above those recommended by the WHO (45 dB), highlighting the need for public health interventions.

Temporal trends and demographic risk factors for hospital admissions due to carbon monoxide poisoning in England.

Unintentional non-fire related (UNFR) carbon monoxide (CO) poisoning is a preventable cause of morbidity and mortality. Epidemiological data on UNFR CO poisoning can help monitor changes in the magnitude of this burden, particularly through comparisons of multiple countries, and to identify vulnerable sub-groups of the population which may be more at risk. Here, we collected data on age- and sex- specific number of hospital admissions with a primary diagnosis of UNFR CO poisoning in England (2002-2016), aggregated to small areas, alongside area-level characteristics (i.e. deprivation, rurality and ethnicity). We analysed temporal trends using piecewise log-linear models and compared them to analogous data obtained for Canada, France, Spain and the US. We estimated age-standardized rates per 100,000 inhabitants by area-level characteristics using the WHO standard population (2000-2025). We then fitted the Besag York Mollie (BYM) model, a Bayesian hierarchical spatial model, to assess the independent effect of each area-level characteristic on the standardized risk of hospitalization. Temporal trends showed significant decreases after 2010. Decreasing trends were also observed across all countries studied, yet France had a 5-fold higher risk. Based on 3399 UNFR CO poisoning hospitalizations, we found an increased risk in areas classified as rural (0.69, 95% CrI: 0.67; 0.80), highly deprived (1.77, 95% CrI: 1.66; 2.10) or with the largest proportion of Asian (1.15, 95% CrI: 1.03; 1.49) or Black population (1.35, 95% CrI: 1.20; 1.80). Our multivariate approach provides strong evidence for the identification of vulnerable populations which can inform prevention policies and targeted interventions.

Software application profile: the Rapid Inquiry Facility 4.0: an open access tool for environmental public health tracking.

The Rapid Inquiry Facility 4.0 (RIF) is a new user-friendly and open-access tool, developed by the UK Small Area Health Statistics Unit (SAHSU), to facilitate environment public health tracking (EPHT) or surveillance (EPHS). The RIF is designed to help public health professionals and academics to rapidly perform exploratory investigations of health and environmental data at the small-area level (e.g. postcode or detailed census areas) in order to identify unusual signals, such as disease clusters and potential environmental hazards, whether localized (e.g. industrial site) or widespread (e.g. air and noise pollution). The RIF allows the use of advanced disease mapping methods, including Bayesian small-area smoothing and complex risk analysis functionalities, while accounting for confounders. The RIF could be particularly useful to monitor spatio-temporal trends in mortality and morbidity associated with cardiovascular diseases, cancers, diabetes and chronic lung diseases, or to conduct local or national studies on air pollution, flooding, low-magnetic fields or nuclear power plants.

Changes in individual and contextual socio-economic level influence on reproductive behavior in Spanish women in the MCC-Spain study.

BACKGROUND: The association between socioeconomic level and reproductive factors has been widely studied. For example, it is well known that women with lower socioeconomic status (SES) tend to have more children, the age at first-born being earlier. However, less is known about to what extent the great socioeconomic changes occurred in a country (Spain) could modify women reproductive factors. The main purpose of this article is to analyze the influence of individual and contextual socioeconomic levels on reproductive factors in Spanish women, and to explore whether this influence has changed over the last decades. METHODS: We performed a cross-sectional design using data from 2038 women recruited as population-based controls in an MCC-Spain case-control study. RESULTS: Higher parent's economic level, education level, occupational level and lower urban vulnerability were associated with higher age at first delivery and lower number of pregnancies. These associations were stronger for women born after 1950: women with unfinished primary education had their first delivery 6 years before women with high education if they were born after 1950 (23.4 vs. 29.8 years) but only 3 years before if they were born before 1950 (25.7 vs. 28.0 years). For women born after 1950, the number of pregnancies dropped from 2.1 (unfinished primary school) to 1.7 (high education), whereas it remained almost unchanged in women born before 1950. CONCLUSIONS: Reproductive behavior was associated with both individual and area-level socio-economic indicators. Such association was stronger for women born after 1950 regarding age at first delivery and number of pregnancies and for women born before 1950 regarding consumption of hormonal contraceptives or postmenopausal therapy.

Risk of respiratory hospital admission associated with modelled concentrations of Aspergillus fumigatus from composting facilities in England.

Bioaerosols have been associated with adverse respiratory-related health effects and are emitted in elevated concentrations from composting facilities. We used modelled Aspergillus fumigatus concentrations, a good indicator for bioaerosol emissions, to assess associations with respiratory-related hospital admissions. Mean daily Aspergillus fumigatus concentrations were estimated for each composting site for first full year of permit issue from 2005 onwards to 2014 for Census Output Areas (COAs) within 4 km of 76 composting facilities in England, as previously described (Williams et al., 2019). We fitted a hierarchical generalized mixed model to examine the risk of hospital admission with a primary diagnosis of (i) any respiratory condition, (ii) respiratory infections, (iii) asthma, (iv) COPD, (v) diseases due to organic dust, and (vi) Cystic Fibrosis, in relation to quartiles of Aspergillus fumigatus concentrations. Models included a random intercept for each COA to account for over-dispersion, nested within composting facility, on which a random intercept was fitted to account for clustering of the data, with adjustments for age, sex, ethnicity, deprivation, tobacco sales (smoking proxy) and traffic load (as a proxy for traffic-related air pollution). We included 249,748 respiratory-related and 3163 Cystic Fibrosis hospital admissions in 9606 COAs with a population-weighted centroid within 4 km of the 76 included composting facilities. After adjustment for confounders, no statistically significant effect was observed for any respiratory-related (Relative Risk (RR) = 0.99; 95% Confidence Interval (CI) 0.96-1.01) or for Cystic Fibrosis (RR = 1.01; 95% CI 0.56-1.83) hospital admissions for COAs in the highest quartile of exposure. Similar results were observed across all respiratory disease sub-groups. This study does not provide evidence for increased risks of respiratory-related hospitalisations for those living near composting facilities. However, given the limitations in the dispersion modelling, risks cannot be completely ruled out. Hospital admissions represent severe respiratory episodes, so further study would be needed to investigate whether bioaerosols emitted from composting facilities have impacts on less severe episodes or respiratory symptoms.

Incidence of sleep apnea and association with atrial fibrillation in an unselected pacemaker population: Results of the observational RESPIRE study.

BACKGROUND: Patients with atrial fibrillation (AF) often have sleep apnea (SA), but diagnosis of SA with polysomnography is costly. SA monitoring is a pacemaker feature that measures respiratory disturbance index, the sum of abnormal respiratory events divided by sleep duration. OBJECTIVE: The purpose of this study was to evaluate the incidence and severity of SA and its association with AF in an unselected population fitted with pacemakers. METHODS: RESPIRE (REgistry of Sleep APnea monItoring and Atrial Fibrillation in pacemakeR patients) was a multicenter, international, observational, open-label study following adult subjects for 18 months after implantation with an SA monitoring-enabled dual-chamber pacemaker. Severe SA was defined as average respiratory disturbance index ≥20 from implantation to follow-up visit. The first co-primary end point was the difference in significant AF (cumulative AF episodes lasting ≥24 hours over 2 consecutive days) between subjects with severe and those nonsevere SA at 12 months in the full analysis set (N = 553). The second co-primary end point was the rate of major serious adverse events at 18 months in the modified intention-to-treat set (N = 1024). RESULTS: Severe SA was detected in 31.1% (172 of 553). A higher incidence of significant AF was reported in patients with severe SA than in patients with nonsevere SA (25.0% vs 13.9%; difference 11.1%; 95% confidence interval 3.7%-18.4%; P = .002). Significant AF increased with time in both groups, but at a faster rate in the severe SA group. No intergroup difference in the overall rate of major serious adverse events was observed (P = .065). CONCLUSION: SA screening over 12 months identified severe SA in almost one-third of unselected patients fitted with pacemakers. Severe SA was associated with a higher incidence of significant AF.

Algorithm-based reduction of inappropriate defibrillator shock: Results of the Inappropriate Shock Reduction wIth PARAD+ Rhythm DiScrimination-Implantable Cardioverter Defibrillator Study.

BACKGROUND: Inappropriate shocks (IS) continue to have a major negative impact on patients implanted with defibrillators. OBJECTIVE: The purpose of this study was to assess IS reduction with the PARAD+ discrimination algorithm in a general population implanted for primary or secondary prevention. METHODS: ISIS-ICD (Inappropriate Shock Reduction wIth PARAD+ Rhythm DiScrimination-Implantable Cardioverter Defibrillator) was a 2-year international, interventional study in patients implanted with a dual implantable cardioverter-defibrillator (ICD) or triple-chamber defibrillator (cardiac resynchronization therapy-defibrillator [CRT-D]) featuring PARAD+. IS (shocks not delivered for ventricular tachycardia or fibrillation) were independently adjudicated. The primary endpoint was percentage of IS-free patients at 24 months. Primary and worst-case analyses of annual incidence rates of patients with ≥1 IS, overall and per defibrillator type, were conducted. RESULTS: In total, 1013 patients (80.7% male; age 67.1 ± 11.4 years; 68%/30%/2% primary/secondary/other indication) were enrolled and followed for a median of 552 days (interquartile range 354; 725). Of 993 analyzed patients programmed with PARAD+, 14 had ≥1 IS, corresponding to a percentage free from IS of 98.1% (95% confidence interval [CI] 96.8%- 98.9%). Annual incidence rates (per 100 person-years) of patients with IS were 1.0 (95% CI 0.59-1.69) and 2.1 (95% CI 1.46-3.02) in the primary and worst-case analyses, respectively. In ICD patients, rates were 1.2 (95% CI 0.68-2.23) and 2.3 (95% CI 1.47-3.53), and in CRT-D patients 0.59 (95% CI 0.19-1.83) and 1.8 (95% CI 0.93-3.44) per 100 person-years. CONCLUSION: The annual rate of defibrillator patients with IS using the enhanced PARAD+ discrimination algorithm alone ranged from 1.0 to 2.1 per 100 person-years in a general population implanted for primary or secondary prevention.

Residential proximity to green spaces and breast cancer risk: The multicase-control study in Spain (MCC-Spain).

BACKGROUND: Breast cancer is the main cause of cancer mortality among women. Green spaces have been recently associated with reduced cancer mortality among women. Mechanisms explaining the beneficial effect of green spaces include increased levels of physical activity and reduced exposure to air pollution, which have been both associated with cancer development. OBJECTIVES: To investigate the associations between presence of urban green areas, presence of agricultural areas and surrounding greenness and risk of breast cancer, and to assess whether these associations are mediated by physical activity and/or air pollution levels. METHODS: We geocoded the current residence of 1129 breast cancer cases and 1619 controls recruited between 2008 and 2013 in ten provinces of Spain, as part of the MCC-Spain study. We assigned different indicators of exposure to green spaces in a buffer of 300 m, and in nested buffers of 100 m and 500 m around the residence: presence of urban green areas according to Urban Atlas, presence of agricultural areas according to CORINE Land Cover 2006, and surrounding greenness according to the average of the Normalized Difference Vegetation Index. We used logistic mixed-effects regression models with a random effect for hospital adjusting for potential confounders. We explored the effect of several potential effect modifiers. We assessed mediation effect by physical activity and levels of air pollution. RESULTS: Presence of urban green areas was associated with reduced risk of breast cancer after adjusting for age, socio-economic status at individual and at area level, education, and number of children [OR (95%CI) = 0.65 (0.49-0.86)]. There was evidence of a linear trend between distance to urban green areas and risk of breast cancer. On the contrary, presence of agricultural areas and surrounding greenness were associated with increased risk of breast cancer [adjusted OR (95%CI) = 1.33 (1.07-1.65) and adjusted OR (95%CI) = 1.27 (0.92-1.77), respectively]. None of the associations observed were mediated by levels of physical activity or levels or air pollution. CONCLUSIONS: The association between green spaces and risk of breast cancer is dependent on land-use. The confirmation of these results in other settings and the study of potential mechanisms for the associations observed are needed to advance the understanding on the potential effects of green spaces on health.

Evaluating the Association between Artificial Light-at-Night Exposure and Breast and Prostate Cancer Risk in Spain (MCC-Spain Study).

BACKGROUND: Night shift work, exposure to light at night (ALAN) and circadian disruption may increase the risk of hormone-dependent cancers. OBJECTIVES: We evaluated the association of exposure to ALAN during sleeping time with breast and prostate cancer in a population based multicase-control study (MCC-Spain), among subjects who had never worked at night. We evaluated chronotype, a characteristic that may relate to adaptation to light at night. METHODS: We enrolled 1,219 breast cancer cases, 1,385 female controls, 623 prostate cancer cases, and 879 male controls from 11 Spanish regions in 2008-2013. Indoor ALAN information was obtained through questionnaires. Outdoor ALAN was analyzed using images from the International Space Station (ISS) available for Barcelona and Madrid for 2012-2013, including data of remotely sensed upward light intensity and blue light spectrum information for each geocoded longest residence of each MCC-Spain subject. RESULTS: Among Barcelona and Madrid participants with information on both indoor and outdoor ALAN, exposure to outdoor ALAN in the blue light spectrum was associated with breast cancer [adjusted odds ratio (OR) for highest vs. lowest tertile, OR=1.47; 95% CI: 1.00, 2.17] and prostate cancer (OR=2.05; 95% CI: 1.38, 3.03). In contrast, those exposed to the highest versus lowest intensity of outdoor ALAN were more likely to be controls than cases, particularly for prostate cancer. Compared with those who reported sleeping in total darkness, men who slept in "quite illuminated" bedrooms had a higher risk of prostate cancer (OR=2.79; 95% CI: 1.55, 5.04), whereas women had a slightly lower risk of breast cancer (OR=0.77; 95% CI: 0.39, 1.51). CONCLUSION: Both prostate and breast cancer were associated with high estimated exposure to outdoor ALAN in the blue-enriched light spectrum. https://doi.org/10.1289/EHP1837.

Long-term exposure to trihalomethanes in drinking water and breast cancer in the Spanish multicase-control study on cancer (MCC-SPAIN).

BACKGROUND: Exposure to trihalomethanes (THMs) in drinking water has consistently been associated with an increased risk of bladder cancer, but evidence on other cancers including the breast is very limited. OBJECTIVES: We assessed long-term exposure to THMs to evaluate the association with female breast cancer (BC) risk. METHODS: A multi case-control study was conducted in Spain from 2008 to 2013. We included 1003 incident BC cases (women 20-85years old) recruited from 14 hospitals and 1458 population controls. Subjects were interviewed to ascertain residential histories and major recognized risk factors for BC. Mean residential levels of chloroform, brominated THMs (Br-THMs) and the sum of both as total THM (TTHMs) during the adult-lifetime were calculated. RESULTS: Mean adult-lifetime residential levels ranged from 0.8 to 145.7µg/L for TTHM (median=30.8), from 0.2 to 62.4µg/L for chloroform (median=19.7) and from 0.3 to 126.0µg/L for Br-THMs (median=9.7). Adult-lifetime residential chloroform was associated with BC (adjusted OR=1.47; 95%CI=1.05, 2.06 for the highest (>24µg/L) vs. lowest (<8µg/L) quartile; p-trend=0.024). No association was detected for residential Br-THMs (OR=0.91; 95%CI=0.68, 1.23 for >31µg/L vs. <6µg/L) or TTHMs (OR=1.14; 95%CI=0.83, 1.57 for >48µg/L vs. <22µg/L). CONCLUSIONS: At common levels in Europe, long-term residential total THMs were not related to female breast cancer. A moderate association with chloroform was suggested at the highest exposure category. This large epidemiological study with extensive exposure assessment overcomes several limitations of previous studies but further studies are needed to confirm these results.

Descriptive epidemiology of primary malignant and non-malignant central nervous tumors in Spain: Results from the Girona Cancer Registry (1994-2013).

BACKGROUND: Systematic registration of non-malignant central nervous system (CNS) tumors is a rare practice among European cancer registries. Thus, the real burden of all CNS tumors across Europe is underestimated. The Girona Cancer Registry provides here the first data on CNS tumor incidence and survival trends in Spain for all histological types, including malignant and non-malignant tumors. METHODS: Data on all incident cases of primary CNS tumors notified to the Girona population-based cancer registry from 1994 to 2013 (n=2,131) were reviewed. Incidences rates (IRs) were standardized to the 2013 European population and annual percentage changes (EAPC) were estimated using a piecewise log linear model. 1- and 5-year observed (OS) and relative survival (RS) were also calculated. Results were expressed by sex, age-group, histological subtype and behavior. RESULTS: The overall IR was 16.85 and increased across the period of study (EAPC=+2.2%). The proportion and IRs of malignant (50.2%; IR=9.35) and non-malignant cases (49.8%; IR=9.14) were similar; however, non-malignant tumors were more frequent in women (sex ratio=0.63). The most frequently reported histologies were meningioma (27.6%; IR=5.11) and glioblastoma (22.2%; IR=4.15), which also accounted for the highest and lowest 5-year RS (80.2%; 3.7%, respectively). Globally, 5-year RS was lower in men (42.6% vs. 58.3%, respectively) and in the elderly (64.9% for 0-14years vs. 23.0% for >74years). CONCLUSION: This study presents a comprehensive overview of the epidemiology of malignant and non-malignant CNS primary tumors from the well-established region-wide Girona Cancer Registry (1994-2013). Incidence rates were recovered for all histologies. Survival is still dramatically associated to both age and histological subtype.

High cancer mortality for US-born Latinos: evidence from California and Texas.

BACKGROUND: Latinos born in the US, 36 million, comprise 65% of all US Latinos. Yet their cancer experience is nearly always analyzed together with their foreign-born counterparts, 19 million, who constitute a steady influx of truly lower-risk populations from abroad. To highlight specific cancer vulnerabilities for US-born Latinos, we compare their cancer mortality to the majority non-Latino white (NLW) population, foreign-born Latinos, and non-Latino blacks. METHODS: We analyzed 465,751 cancer deaths from 2008 to 2012 occurring among residents of California and Texas, the two most populous states, accounting for 47% of US Latinos. This cross-sectional analysis, based on granular data obtained from death certificates on cause of death, age, race, ethnicity and birthplace, makes use of normal standardization techniques and negative binomial regression models. RESULTS: While Latinos overall have lower all-cancers-combined mortality rates than NLWs, these numbers were largely driven by low rates among the foreign born while mortality rates for US-born Latinos approach those of NLWs. Among Texas males, rates were 210 per 100,000 for NLWs and 166 for Latinos combined, but 201 per 100,000 for US-born Latinos and 125 for foreign-born Latinos. Compared to NLWs, US-born Latino males in California had mortality rate ratios of 2.83 (95% CI: 2.52-3.18) for liver cancer, 1.44 (95% CI: 1.30-1.61) for kidney cancer, and 1.25 (95% CI: 1.17-1.34) for colorectal cancer (CRC). Texas results showed a similar site-specific pattern. CONCLUSIONS: Specific cancer patterns for US-born Latinos, who have relatively high cancer mortality, similar overall to NLWs, are masked by aggregation of all Latinos, US-born and foreign-born. While NLWs had high mortality for lung cancer, US-born Latinos had high mortality for liver, kidney and male colorectal cancers. HCV testing and reinforcement of the need for CRC screening should be a priority in this specific and understudied population. The unprecedented proximity of overall rates between NLWs and US-born Latino populations runs counter to the prevailing narrative of Latinos having significantly lower cancer risk and mortality. Birthplace data are critical in detecting meaningful differences among Latinos; these findings merit not only clinical but also public health attention.

Myocardial motion and deformation patterns in an experimental swine model of acute LBBB/CRT and chronic infarct.

In cardiac resynchronization therapy (CRT), specific changes in motion/deformation happen with left-bundle-branch-block (LBBB) and following treatment. However, they remain sub-optimally studied. We propose a two-fold improvement of their characterization. This includes controlling them through an experimental model and using more suitable quantification techniques. We used a swine model of acute LBBB and CRT with/without chronic infarct (pure-LBBB: N = 11; LBBB + left-anterior-descending infarct: N = 11). Myocardial displacement, velocity and strain were extracted from short-axis echocardiographic sequences using 2D speckle-tracking. The data was transformed to a single spatiotemporal system of coordinates to perform subject comparisons and quantify pattern changes at similar locations and instants. Pure-LBBB animals showed a specific intra-ventricular dyssynchrony pattern with LBBB (11/11 animals), and the recovery towards a normal pattern with CRT (10/11 animals). Pattern variability was low within the pure-LBBB population, as quantified by our method. This was not correctly assessed by more conventional measurements. Infarct presence affected the pattern distribution and CRT efficiency (improvements in 6/11 animals). Pattern changes correlated with global cardiac function (global circumferential strain) changes in all the animals (corrected: (pLBBBvsBaseline) < 0.001, (pCRTvsBaseline) = NS; non-corrected: (pLBBBvsBaseline) = NS, (pCRTvsBaseline) = 0.028). Our LBBB/CRT experimental model allowed controlling specific factors responsible for changes in mechanical dyssynchrony and therapy. We illustrated the importance of our quantification method to study these changes and their variability. Our findings confirm the importance of myocardial viability and of specific LBBB-related mechanical dyssynchrony patterns.

Development of a swine model of left bundle branch block for experimental studies of cardiac resynchronization therapy.

Animal models that mimic human electrical and mechanical dyssynchrony often associated with chronic heart failure would provide an essential tool to investigate factors influencing response to cardiac resynchronization therapy. A standardized closed-chest porcine model of left bundle branch block (LBBB) was developed using 16 pigs. Radiofrequency applications were performed to induce LBBB, which was confirmed by QRS widening, a surface electrocardiogram pattern concordant with LBBB, and a prolonged activation time from endocardial. Echocardiography confirmed abnormal motion of the septum, which was not present at the baseline echocardiogram. High susceptibility of pigs to ventricular fibrillation during the endocardial ablation was overcome by applying high-rate pacing during radiofrequency applications. This is the first study to devise a closed-chest porcine model of LBBB that closely reproduces abnormalities found in patients with electrical and mechanical cardiac dyssynchrony, and provides a useful tool to investigate the basic mechanisms underlying cardiac resynchronization therapy benefits in heart failure.