Longitudinal analysis of thoracic aortic expansion in non-syndromic real-world patients.

Remodeling of the thoracic aorta is commonly seen and viewed as a precursor to an aortic aneurysm. However, while aneurysms have been shown to expand at a rate of approximately 1 mm annually, the expansion of the pre-aneurysmal aorta is poorly characterized, especially in relation to age, gender, and aortic size per se. We identified patients that had undergone echocardiography at least twice at a large university medical center. Diagnosis codes, medications, and blood test results were obtained from hospital records. Syndromic patients were excluded (e.g., Marfan's syndrome, bicuspid aortic valve). Final population comprised n = 24,928 patients (median age 61.2 years (inter-quartile range (IQR): 50.6-71.5); 55.8% males) that had undergone a median of 3 echocardiograms (2-4; range 2-27) during a median of 4.0 years (IQR: 2.3-6.2). Hypertension was present in 39.6% of patients and diabetes in 20.7%, median LV ejection fraction was 56.0% (IQR: 41.0-62.0). Aortic size measurements were analyzed in mixed models while clustering on individual patients. Mean expansion was determined for sinus of Valsalva as 1.93 (95% confidence interval; CI95: 1.87-1.99) mm per decade, and for ascending aorta as 1.76 (CI95: 1.70-1.82) mm per decade. Faster expansion was found in males, with larger aortic size, and younger age (p for interaction <0.05 for all). In conclusion, expansion of the thoracic aorta, in real world, non-syndromic patients, is slow and averages <2 mm per decade. This will help to inform management of this large patient group.

Direct Oral Anticoagulation Versus Warfarin in Left Ventricular Thrombus: Pooled Analysis of Randomized Controlled Trials.

Patients with impaired left ventricular (LV) function can develop LV thrombus, a potentially life-threatening condition due to risk of stroke and embolization. Conventional treatment with vitamin K antagonists (VKAs; e.g., warfarin) puts patients at risk of bleeding, and the use of direct oral anticoagulants (DOACs) appears promising, although data are scant. We searched the published English language literature for randomized controlled trials (RCTs) comparing DOACs with VKAs in LV thrombus. End points were failure to resolve, thromboembolic events (stroke, embolism), bleeding, or any adverse event (composite of thromboembolism or bleeding), or all-cause death. Data were pooled and analyzed in hierarchical Bayesian models. In three eligible RCTs, 141 patients were studied during an average of 4.6 months (53.8 patient-years; n = 71 assigned to DOAC, n = 70 assigned to VKA). A similar number of patients in each treatment arm demonstrated failure to resolve (DOAC: 14/71 vs. VKA: 15/70) and death events (3/71 vs. 4/70). However, patients on DOACs suffered fewer strokes/thromboembolic events (1/71 vs. 7/70; log odds ratio [OR], -2.02 [95% credible interval (CI95 ), -4.53 to -0.31]) and fewer bleeding events (2/71 vs. 9/70; log OR, -1.62 [CI95 , -3.43 to -0.26]), leading to fewer patients on DOACs with any adverse event versus VKAs (3/71 vs. 16/70; log OR, -1.93 [CI95 , -3.33 to -0.75]). In conclusion, pooled analysis of RCT data favors DOACs over VKAs in patients with LV thrombus in terms of both efficacy and safety.

The clinical value and cost-effectiveness of treatments for patients with coronary artery disease.

BACKGROUND: The clinical value and cost-effectiveness of invasive treatments for patients with coronary artery disease is unclear. Invasive treatments such as coronary artery bypass grafting and percutaneous coronary intervention are frequently used as a starting treatment, yet they are much more costly than optimal medical therapy. While patients may transition into other treatments over time, the choices of starting treatments are likely important determinants of costs and health outcomes. The aim is to predict by how much costs and health outcomes will change from a decision to use different starting treatments for patients with coronary artery disease in an Asian setting. METHODS: A cost-effectiveness study using a Markov model informed by data from Singapore General Hospital was done. All patients with initial presentations of stable coronary disease and no acute coronary syndromes who received medical treatments and interventional therapies were included. We compare existing practice, where the starting treatment can be medical therapy or stent percutaneous coronary interventions or coronary artery bypass grafting, with alternate starting treatment strategies. RESULTS: When compared to 'existing practice' a policy of starting 14% of patients with coronary artery bypass grafting and 86% with optimal medical therapy showed savings of $1,743 per patient and 0.23 additional quality adjusted life years. A change to policy nationwide would save $10 million and generate 1,380 quality adjusted life years. CONCLUSIONS: Increasing coronary artery bypass grafting and use of medical therapy in the setting of coronary artery disease is likely to saves costs and improve health outcomes. A definitive study to address the question we investigate would be very difficult to undertake and so using existing data to model the expected outcomes is a useful tool. There are likely to be large and complex barriers to the implementation of any policy change based on the findings of this study.

Predicting premature termination of exercise during Bruce protocol stress echocardiography.

AIMS: Clinical guidelines recommend that the exercise protocol of a stress echocardiogram is selected to induce volitional exhaustion after a target duration of at least 8 minutes. While the Bruce protocol is very commonly used for clinical stress tests, it is known to be "steep", and many patients therefore fail to reach 8 minutes. We studied predictors of failure and developed a method for identifying patients not suitable for Bruce protocol which was accurate and yet simple enough to be used as a point-of-care decision support tool. METHODS AND RESULTS: We studied data out-patients undergoing Bruce protocol stress echocardiograms (n = 11 086) and analyzed predictors of inappropriate early termination (defined as test duration < 8 min as per current practice guidelines) using logistic regression. A prediction model was constructed as follows: .5 points were given for each of hypertension, diabetes, smoking, and E/e' > 7.9 in the resting echocardiogram; .1 point was added for each 1-unit increment in body mass index; 1 point was added for patient age by decade; 2.0 points were subtracted for male sex (p for all < 0.001). In tests on held-out validation data, the model was well calibrated (in plots of predicted vs actual risk) and discriminated failure versus non-failure well (C-statistic .86 for a score of 6.0 points; p < 0.001). CONCLUSION: These data may help to standardize protocol selection in stress echocardiography, by identifying patients pre-hoc where Bruce protocol will be inappropriately steep.

Diastolic function and its association with diabetes, hypertension and age in an outpatient population with normal stress echocardiography findings.

BACKGROUND: Diastolic dysfunction can be caused by hypertension or diabetes mellitus, and it is also often found with increasing age. In a given patient, the cause of diastolic dysfunction is therefore not always obvious. We sought to study the interplay of these risk factors for diastolic dysfunction in an outpatient population with a low likelihood of ischemic heart disease. METHODS: Consecutive patients referred for stress echocardiography were included retrospectively. Exclusion criteria included pathological stress response, atrial arrhythmia, left ventricular ejection fraction < 55%, and more than mild valvular disease. Standard diastolic parameters were recorded in all patients. In a subset of patients, mechanistic analysis of early filling was performed using the parameterized diastolic filling (PDF) method. RESULTS: We included 726 patients (median [interquartile range] age 56 (44-65) years, 57% male). The prevalence of diabetes and hypertension was 43 and 49%, respectively. In multiple linear regression modeling, the presence of diabetes, hypertension, sex and increasing age explained a moderate amount of the variance in e' velocities, E/A ratio and E/e' (R2 = 0.31-0.48, p < 0.001), and a low amount of the variance in left atrial volume index (LAVI) and the PDF parameters (n = 446, R2 = 0.05-0.17, p < 0.001). Sex was only related to LAVI and E/e' for the conventional parameters (beta - 0.94, p = 0.04, and beta - 0.91, p < 0.001, respectively). CONCLUSIONS: Diabetes, hypertension, increasing age, and to a lesser extent sex, explain a moderate amount of the variance in conventional diastolic parameters related to myocardial tissue velocities and E/A ratio in a healthy outpatient population. The effect of these risk factors was substantially less pronounced on left atrial volume index and the PDF parameters.

Beta-blockers and renin-angiotensin system inhibitors in acute myocardial infarction managed with inhospital coronary revascularization.

Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70-0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55-0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66-0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68-0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57-0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40-0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48-0.86). This were consistent for left ventricular ejection fraction < 50% or ≥ 50%. In conclusion, in AMI managed with revascularization, both BB and ACEI/ARB were associated with a lower incidence of 12-month all-cause mortality. Combined BB and ACEI/ARB was associated with the lowest incidence of all-cause mortality and HF hospitalization.

E/e' in relation to outcomes in ST-elevation myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a high-risk condition especially when filling pressure is raised, and earlier reports have suggested that E/e' is associated with poor outcome. However, whether E/e' predicts risk better than LVEF, which is the current standard of practice, is not known. We investigated this question in the largest and most rigorous study of MI patients so far. METHODS AND RESULTS: We studied 660 patients with ST-elevation MI (STEMI) treated with primary percutaneous coronary intervention and related E/e' to short-term mortality (in-hospital death), as well as long-term events at 2 years comprising (a) a composite of MI, stroke, heart failure, and death, and (b) death alone. Short-term models were adjusted for age, sex, and LVEF. Long-term models were adjusted for age, sex, diabetes, revascularization procedure, history of MI, hypertension, renal function, drugs on discharge, and LVEF. Elevated E/e'> 15 indicated higher risk of short-term events (n = 19:7.0% (95% confidence interval 3.4-10.8%) vs. 1.0% (0.3 - 2.3%); adjusted odds ratio 3.7 (1.3-10.5)). While elevated E/e' was also associated with long-term outcomes (n = 103 composite events: 15.9% (11.9% - 21.4%) vs 6.8% (5.2% - 8.7%), P < .001; n = 38 death events: 6.0% (3.9% - 9.5%) vs 2.0% (1.3% - 3.2%), P = .001), E/e' was rendered nonsignificant for long-term outcomes by multivariable adjustment (p = ns for both). LVEF, on the contrary, was a highly significant predictor in the adjusted long-term model. CONCLUSION: E/e' is associated with poor outcome in STEMI, but LVEF is a stronger predictor of long-term risk.

Performance of cardiac troponins within the HEART score in predicting major adverse cardiac events at the emergency department.

BACKGROUND: This study compared the performance of a single blood draw of high-sensitivity troponin T (hsTnT), high-sensitivity troponin I (hsTnI) and conventional troponin I (cTnI) within a modified HEART score for predicting 30-day MACE at Emergency Department (ED) presentation, and established local reference norms for all three assays by determining the cut-off point which yielded the highest sensitivity and negative predictive value for acute myocardial infarction and 30-day MACE. METHODS: This single-center prospective cohort study recruited chest pain patients at the ED, whose hsTnT, hsTnI and cTnI were taken on admission. Subjects were classified into low and non-low risk group according to their modified HEART score, with MACE as the primary endpoint. Receiver-operating characteristic (ROC) curves were generated, area under the curves (AUCs) were calculated; the performance characteristics were determined. RESULTS: The performance of modified HEART scores was comparable among the three assays for 30-day MACE (84.9-87.0% sensitivity, 95.6-96.0% NPV, 95%CI) and none of these had very high AUC and specificity (AUC 0.70-0.71, 53.7-56.7% specificity, 95% CI). The modified HEART score using a single blood draw of either hsTnT (3.9ng/L), hsTnI (0.9ng/L) or cTnI (0.0ng/L) at presentation yielded a sensitivity of 100% for 30-day MACE. CONCLUSION: The modified HEART score using a single blood draw of either hsTnT, hsTnI or cTnI was equally effective in risk-stratifying chest pain patients for safe discharge. The theoretical cut-off points yielding 100% sensitivity are potentially useful (when achieved) for safely discharging low risk patients with undifferentiated chest pain in the ED.

Harnessing technology and molecular analysis to understand the development of cardiovascular diseases in Asia: a prospective cohort study (SingHEART).

BACKGROUND: Cardiovascular disease (CVD) imposes much mortality and morbidity worldwide. The use of "deep learning", advancements in genomics, metabolomics, proteomics and devices like wearables have the potential to unearth new insights in the field of cardiology. Currently, in Asia, there are no studies that combine the use of conventional clinical information with these advanced technologies. We aim to harness these new technologies to understand the development of cardiovascular disease in Asia. METHODS: Singapore is a multi-ethnic country in Asia with well-represented diverse ethnicities including Chinese, Malays and Indians. The SingHEART study is the first technology driven multi-ethnic prospective population-based study of healthy Asians. Healthy male and female subjects aged 21-69 years old without any prior cardiovascular disease or diabetes mellitus will be recruited from the general population. All subjects are consented to undergo a detailed on-line questionnaire, basic blood investigations, resting and continuous electrocardiogram and blood pressure monitoring, activity and sleep tracking, calcium score, cardiac magnetic resonance imaging, whole genome sequencing and lipidomic analysis. Outcomes studied will include mortality and cause of mortality, myocardial infarction, stroke, malignancy, heart failure, and the development of co-morbidities. DISCUSSION: An initial target of 2500 patients has been set. From October 2015 to May 2017, an initial 683 subjects have been recruited and have completed the initial work-up the SingHEART project is the first contemporary population-based study in Asia that will include whole genome sequencing and deep phenotyping: including advanced imaging and wearable data, to better understand the development of cardiovascular disease across different ethnic groups in Asia.

Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging.

Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST; they included age, gender, occupation and alcohol consumption. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with cardiovascular disease risk markers such as body mass index and waist circumference, whereas self-reported measures were not. Using wearable-derived TST, we showed that insufficient sleep was associated with premature telomere attrition. Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies.

Independent Predictors of Cardiac Mortality and Hospitalization for Heart Failure in a Multi-Ethnic Asian ST-segment Elevation Myocardial Infarction Population Treated by Primary Percutaneous Coronary Intervention.

We aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention.

Particulate air pollution on cardiovascular mortality in the tropics: impact on the elderly.

BACKGROUND: Air pollution has a significant health impact. Most data originate from temperate regions. We aim to study the health impact of air pollution, particularly among the elderly, in a tropical region. METHODS: A daily time-series analysis was performed to estimate excess risk (ER) of various air pollutants on daily death counts amongst the general population in Singapore from 2001 to 2013. Air pollutants included particulate matters smaller than 10 µm, and 2.5 µm (PM10, PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3) and sulphur dioxide (SO2). The studied outcomes were non-accidental and cardiovascular mortality. Single-day lag and distributed lag models were studied and adjusted for confounders. RESULTS: In single-day lag models, a 10 µg/m3 increase in particulate matter was associated with significant increases in non-accidental (PM10 ER: 0.627%; 95% confidence interval (CI): 0.260-0.995% and PM2.5 ER: 0.660%; 95% CI: 0.204-1.118%) and cardiovascular mortality (PM10 ER: 0.897; 95% CI: 0.283-1.516 and PM2.5 ER: 0.883%; 95% CI: 0.121-1.621%). This was significant in the elderly ≥ 65 years but not in those < 65 years and were seen in the acute phase of lag 0-5 days. Effects by other pollutants were minimal. For cardiovascular mortality, the effects turned protective at a cumulative lag of 30 days in the elderly and could due to "harvesting". CONCLUSIONS: These first contemporary population-based data from an equatorial country with tropical climate show that exposure to particulate air pollution was significantly associated with non-accidental mortality and cardiovascular mortality, especially in the elderly.

Sex Differences in 1-Year Rehospitalization for Heart Failure and Myocardial Infarction After Primary Percutaneous Coronary Intervention.

It is unclear whether universal access to primary percutaneous coronary intervention (pPCI) may reduce sex differences in 1-year rehospitalization for heart failure (HF) and myocardial infarction (MI) after ST-elevation myocardial infarction (STEMI). We studied 7,597 consecutive STEMI patients (13.8% women, n = 1,045) who underwent pPCI from January 2007 to December 2013. Cox regression models adjusted for competing risk from death were used to assess sex differences in rehospitalization for HF and MI within 1 year from discharge. Compared with men, women were older (median age 67.6 vs 56.0 years, p < 0.001) with higher prevalence of co-morbidities and multivessel disease. Women had longer median door-to-balloon time (76 vs 66 minutes, p < 0.001) and were less likely to receive drug-eluting stents (19.5% vs 24.1%, p = 0.001). Of the medications prescribed at discharge, fewer women received aspirin (95.8% vs 97.6%, p = 0.002) and P2Y12 antagonists (97.6% vs 98.5%, p = 0.039), but there were no significant sex differences in other discharge medications. After adjusting for differences in baseline characteristics and treatment, sex differences in risk of rehospitalization for HF attenuated (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.79 to 1.40), but persisted for MI (HR 1.68, 95% CI 1.22 to 2.33), with greater disparity in patients aged ≥60 years (HR 1.83, 95% CI 1.18 to 2.85) than those aged <60 years (HR 1.45, 95% CI 0.84 to 2.50). In conclusion, in a setting of universal access to pPCI, the adjusted risk of 1-year rehospitalization for HF was similar in both sexes, but women had significantly higher adjusted risk of 1-year rehospitalization for MI, especially older women.

Building a Longitudinal National Integrated Cardiovascular Database　- Lessons Learnt From SingCLOUD.

Background: Real world data on clinical outcomes and quality of care for patients with coronary artery disease (CAD) are fragmented. We describe the rationale and design of the Singapore Cardiovascular Longitudinal Outcomes Database (SingCLOUD). Methods and Results: We designed a health data grid to integrate clinical, administrative, laboratory, procedural, prescription and financial data from all public-funded hospitals and primary care clinics, which provide 80% of health care in Singapore. Here, we explain our approach to harmonize real-world data from diverse electronic medical and non-medical platforms to develop a robust and longitudinal dataset. We present pilot data on patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) between 2012 and 2014. The initial data set had 53,395 patients. Of these, 35,203 had CAD confirmed on coronary angiography, of whom 21,521 had PCI. Eventually, limiting to 2012-2014, 3,819 patients had MI with PCI, while 5,989 had MI. Compared with the quality improvement registry, Singapore Cardiac Data Bank, which had 189 fields for analysis, the SingCLOUD platform generated an additional 313 additional data fields, and was able to identify an additional 250 heart failure events, 664 major adverse cardiovascular events at 2 years, and low-density lipoprotein levels to 1 year for 3,747 patients. Conclusions: By integrating multiple incongruent data sources, SINGCLOUD enables in-depth analysis of real-world cardiovascular "big data".

Defining a 'frequent admitter' phenotype among patients with repeat heart failure admissions.

AIMS: We aimed to identify a 'frequent admitter' phenotype among patients admitted for acute decompensated heart failure (HF). METHODS AND RESULTS: We studied 10 363 patients in a population-based prospective HF registry (2008-2012), segregated into clusters based on their 3-year HF readmission frequency trajectories. Using receiver-operating characteristic analysis, we identified the index year readmission frequency threshold that most accurately predicts HF admission frequency clusters. Two clusters of HF patients were identified: a high frequency cluster (90.9%, mean 2.35 ± 3.68 admissions/year) and a low frequency cluster (9.1%, mean 0.50 ± 0.81 admission/year). An index year threshold of two admissions was optimal for distinguishing between clusters. Based on this threshold, 'frequent admitters', defined as patients with ≥ 2 HF admissions in the index year (n = 2587), were of younger age (68 ± 13 vs 69 ± 13 years), more often male (58% vs. 54%), smokers (38.4% vs. 34.4%) and had lower left ventricular ejection fraction (37 ± 17 vs. 41 ± 17%) compared to 'non-frequent admitters' (< 2 HF admissions in the index year; n = 7776) (all P < 0.001). Despite similar rates of advanced care utilization, frequent admitters had longer length of stay (median 4.3 vs. 4.0 days), higher annual inpatient costs (€ 7015 vs. € 2967) and higher all-cause mortality at 3 years compared to the non-frequent admitters (adjusted odds ratio 2.33, 95% confidence interval 2.11-2.58; P < 0.001). CONCLUSION: 'Frequent admitters' have distinct clinical characteristics and worse outcomes compared to non-frequent admitters. This study may provide a means of anticipating the HF readmission burden and thereby aid in healthcare resource distribution relative to the HF admission frequency phenotype.

Air pollution in relation to very short-term risk of ST-segment elevation myocardial infarction: Case-crossover analysis of SWEDEHEART.

OBJECTIVE: Studies have related air pollution to myocardial infarction (MI) events over days or weeks, with few data on very short-term risks. We studied risk of ST-segment elevation MI (STEMI) within hours of exposure to air pollution while adjusting for weather. METHODS: We performed a case-crossover study of STEMI cases in Stockholm, Sweden (Jan 2000-June 2014) based on SWEDEHEART. Exposures during hazard periods up to 24 h prior to admission were compared to bidirectionally sampled control periods. Risks attributable to sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone and particulate pollutants (PM2.5, PM10) were studied in conditional logistic regression models for interquartile range increments. RESULTS: Risk of STEMI (n = 14,601) was associated with NO2 (strongest at 15-h lag) and with PM2.5 (strongest at 20-h lag), in single-pollutant models adjusting for air temperature and humidity (NO2: odds ratio (OR; 95% confidence interval) 1.065 (1.031-1.101); PM2.5: 1.026 (1.001-1.054)). After adjusting models for atmospheric pressure (significantly associated with STEMI risk at 14-24-h lags), NO2 remained highly statistically significant (1.057 (1.022-1.094)) but not PM2.5 (1.024 (0.997-1.052)). No associations were seen for SO2, ozone or PM10. CONCLUSION: Risk of STEMI rises within hours of exposure to air pollutants, with strongest impact of NO2. These findings are complementary to earlier reports which have not acknowledged widely the importance of very short-term fluctuations in air pollution.

Association of Weather With Day-to-Day Incidence of Myocardial Infarction: A SWEDEHEART Nationwide Observational Study.

Importance: Whether certain weather conditions modulate the onset of myocardial infarction (MI) is of great interest to clinicians because it could be used to prevent MIs as well as guide allocation of health care resources. Objective: To determine if weather is associated with day-to-day incidence of MI. Design, Setting, and Participants: In this prospective, population-based and nationwide setting, daily weather data from the Swedish Meteorological and Hydrological Institute were extracted for all MIs reported to the Swedish nationwide coronary care unit registry, Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART), during 1998 to 2013 and then merged with each MI on date of symptom onset and coronary care unit. All patients admitted to any coronary care unit in Sweden owing to MI were included. A total of 280 873 patients were included, of whom 92 044 were diagnosed as having ST-elevation MI. Weather data were available for 274 029 patients (97.6%), which composed the final study population. Data were analyzed between February 2017 and April 2018. Exposures: The nationwide daily mean air temperature, minimum air temperature, maximum air temperature, wind velocity, sunshine duration, atmospheric air pressure, air humidity, snow precipitation, rain precipitation, and change in air temperature. Main Outcomes and Measures: The nationwide daily counts of MI as outcome. Results: In 274 029 patients, mean (SD) age was 71.7 (12) years. Incidence of MI increased with lower air temperature, lower atmospheric air pressure, higher wind velocity, and shorter sunshine duration. The most pronounced association was observed for air temperature, where a 1-SD increase in air temperature (7.4°C) was associated with a 2.8% reduction in risk of MI (unadjusted incidence ratio, 0.972; 95% CI, 0.967-0.977; P <.001). Results were consistent for non-ST-elevation MI as well as ST-elevation MI and across a large range of subgroups and health care regions. Conclusions and Relevance: In this large, nationwide study, low air temperature, low atmospheric air pressure, high wind velocity, and shorter sunshine duration were associated with risk of MI with the most evident association observed for air temperature.

First Medical Contact-to-Device Time and Heart Failure Outcomes Among Patients Undergoing Primary Percutaneous Coronary Intervention.

Background Expediting reperfusion during primary percutaneous coronary intervention is aimed at salvaging myocardium in ST-segment-elevation myocardial infarction. Few studies have examined the relation between reperfusion time and heart failure (HF) events. Methods and Results: We studied 7597 patients undergoing primary percutaneous coronary intervention from 2007 to 2013 in the Singapore Myocardial Infarct Registry, which captures HF at admission, postadmission in-hospital HF, and HF rehospitalization. We studied the relation of first medical contact to deployment of first device to achieve reperfusion (FTD) time with in-hospital HF events and HF rehospitalization, with mortality modeled as a competing risk. At the population level, median FTD time decreased from 91 minutes (interquartile range, 69-114) in 2007 to 58 minutes (45-75) in 2013 ( P=0.001), whereas mortality remained unchanged (in-hospital: range 5.3%-7.3%; P=0.190 and 1-year: range 7.8%-10.9%; P=0.505). HF at admission increased from 12.2% in 2007 to 18.4% in 2013, P=0.020, whereas postadmission in-hospital HF decreased from 12.8% in 2007 to 7.1% in 2013, P=0.030. HF rehospitalization increased from 1.2% in 2007 to 2.6% in 2013 ( P=0.003), for 30-day HF rehospitalization, and 3.8% in 2007 to 5.6% in 2013 ( P=0.037), for 1-year HF rehospitalization. At the individual level, among patients with HF at admission (N=1191), longer FTD time was associated with more 30-day HF rehospitalization (compared with ≤60 minutes, adjusted hazard ratio, 1.68 [0.73-3.86] for 60-90 minutes, 2.88 [1.19-6.92], for 90-120 minutes, and 2.84 [1.08-7.44] for >120 minutes). Longer FTD time was associated with a greater risk of postadmission in-hospital HF (compared with ≤60 minutes, adjusted hazard ratio, 1.18 [0.96-1.44] for 60-90 minutes, 1.59 [1.25-2.03] for 90-120 minutes, and 1.67 [1.26-2.21] for >120 minutes). Conclusions: Temporal reductions in FTD time were associated with decrease in postadmission in-hospital HF. Among patients presenting with HF at admission, delays in FTD beyond 90 minutes were associated with more 30-day HF rehospitalization.

Normal Reference Values for Assessing Diastolic Function Using the Parameterized Diastolic Filling Formalism Method in Patients with Normal Results of Rest and Stress Echocardiography.

The parameterized diastolic filling (PDF) method can be used to study the mechanics of early diastolic left ventricular (LV) filling. However, there are no publications describing the reference ranges of the PDF parameters. This study retrospectively recruited patients with normal results on rest and stress echocardiography and no diabetes or hypertension (n=138, 45% female). DICOM images of the resting E-wave from transmitral pulsed wave Doppler flow velocities were analyzed using freely available software. Viscoelastic energy loss (c) and stiffness (k) were higher in males compared to females (p≤0.001 for both). There were no correlations between any of the PDF parameters and age (p>0.05 for all). In males, stiffness was correlated with systolic blood pressure (r=0.24, p=0.04), and load and filling energy were correlated with diastolic blood pressure (r=-0.27, p=0.02, and r=-0.29, p=0.01, respectively). Sex-specific normal 95% reference limits for PDF analysis of early LV filling are presented for clinical use.