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Background: Obstetrical complications impact the health of mothers and offspring along the life course, resulting in an increased burden of chronic diseases. One specific complication is abruption, a life-threatening condition with consequences for cardiovascular health that remains poorly studied., Objectives: To describe the design and data linkage algorithms for the Placental Abruption and Cardiovascular Event Risk (PACER) cohort., Population: All subjects who delivered in New Jersey, USA, between 1993 and 2020., Design: Retrospective, population-based, birth cohort study., Methods: We linked the vital records data of foetal deaths and live births to delivery and all subsequent hospitalisations along the life course for birthing persons and newborns. The linkage was based on a probabilistic record-matching algorithm., Preliminary Results: Over the 28 years of follow-up, we identified 1,877,824 birthing persons with 3,093,241 deliveries (1.1%, n = 33,058 abruption prevalence). The linkage rates for live births-hospitalisations and foetal deaths-hospitalisations were 92.4% (n = 2,842,012) and 70.7% (n = 13,796), respectively, for the maternal cohort. The corresponding linkage rate for the live births-hospitalisations for the offspring cohort was 70.3% (n = 2,160,736). The median (interquartile range) follow-up for the maternal and offspring cohorts was 15.4 (8.1, 22.4) and 14.4 (7.4, 21.0) years, respectively. We will undertake multiple imputations for missing data and develop inverse probability weights to account for selection bias owing to unlinked records., Conclusions: Pregnancy offers a unique window to study chronic diseases along the life course and efforts to identify the aetiology of abruption may provide important insights into the causes of future CVD. This project presents an unprecedented opportunity to understand how abruption may predispose women and their offspring to develop CVD complications and chronic conditions later in life., (© 2024 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Guidelines for cardiac catheterization in patients with non-specific chest pain (NSCP) provide significant room for provider discretion, which has resulted in variability in the utilization of invasive coronary angiograms (CAs) and a high rate of normal angiograms. The overutilization of CAs in patients with NSCP and discharged without a diagnosis of coronary artery disease is an important issue in medical care quality. As a result, we sought to identify patient demographic, socioeconomic, and geographic factors that influenced the performance of a CA in patients with NSCP who were discharged without a diagnosis of coronary artery disease. We intended to establish reference data points for gauging the success of new initiatives for the evaluation of this patient population. In this 20-year retrospective cohort study (1994-2014), we examined 107 796 patients with NSCP from the Myocardial Infarction Data Acquisition System, a large statewide validated database that contains discharge data for all patients with cardiovascular disease admitted to every non-federal hospital in NJ. Patients were partitioned into two groups: those offered a CA (CA group; n = 12 541) and those that were not (No-CA group; n = 95 255). Geographic, demographic, and socioeconomic variables were compared between the two groups using multivariable logistic regression, which determined the predictive value of each categorical variable on the odds of receiving a CA. Whites were more likely than Blacks and other racial counterparts (19.7% vs. 5.6% and 16.5%, respectively; P < .001) to receive a CA. Geographically, patients who received a CA were more likely admitted to a large hospital compared to small- or medium-sized ones (12.5% vs. 8.9% and 9.7%, respectively; P < .05), a primary teaching institution rather than a teaching affiliate or community center (16.1 % vs. 14.3% and 9.1%, respectively; P < .001), and at a non-rural facility compared to a rural one (12.1% vs. 6.5%; P < .001). Lastly from a socioeconomic standpoint, patients with commercial insurance more often received a CA compared to those having Medicare or Medicaid/self-pay (13.7% vs. 9.5% and 6.0%, respectively; P < .001). The utilization of CA in patients with NSCP discharged without a diagnosis of coronary artery disease in NJ during the study period may be explained by differences in geographic, demographic, and socioeconomic factors. Patients with NSCP should be well scrutinized for CA eligibility, and reliable strategies are needed to reduce discretionary medical decisions and improve quality of care., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level., Methods: In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days., Results: A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49)., Conclusions: In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Despite the decline in the rate of coronary heart disease (CHD) mortality, it is unknown how the 3 strong and modifiable risk factors - alcohol, smoking, and obesity -have impacted these trends. We examine changes in CHD mortality rates in the United States and estimate the preventable fraction of CHD deaths by eliminating CHD risk factors., Methods: We performed a sequential time-series analysis to examine mortality trends among females and males aged 25 to 84 years in the United States, 1990-2019, with CHD recorded as the underlying cause of death. We also examined mortality rates from chronic ischemic heart disease (IHD), acute myocardial infarction (AMI), and atherosclerotic heart disease (AHD). All underlying causes of CHD deaths were classified based on the International Classification of Disease 9th and 10th revisions. We estimated the preventable fraction of CHD deaths attributable to alcohol, smoking, and high body-mass index (BMI) through the Global Burden of Disease., Results: Among females (3,452,043 CHD deaths; mean [standard deviation, SD] age 49.3 [15.7] years), the age-standardized CHD mortality rate declined from 210.5 in 1990 to 66.8 per 100,000 in 2019 (annual change -4.04%, 95% CI -4.05, -4.03; incidence rate ratio [IRR] 0.32, 95% CI, 0.41, 0.43). Among males (5,572,629 CHD deaths; mean [SD] age 47.9 [15.1] years), the age-standardized CHD mortality rate declined from 442.4 to 156.7 per 100,000 (annual change -3.74%, 95% CI, -3.75, -3.74; IRR 0.36, 95% CI, 0.35, 0.37). A slowing of the decline in CHD mortality rates among younger cohorts was evident. Correction for unmeasured confounders through a quantitative bias analysis slightly attenuated the decline. Half of all CHD deaths could have been prevented with the elimination of smoking, alcohol, and obesity, including 1,726,022 female and 2,897,767 male CHD deaths between 1990 and 2019., Conclusions: The decline in CHD mortality is slowing among younger cohorts. The complex dynamics of risk factors appear to shape mortality rates, underscoring the importance of targeted strategies to reduce modifiable risk factors that contribute to CHD mortality., Competing Interests: Disclosures None reported., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Whether changes in stroke mortality are affected by age distribution and birth cohorts, and if the decline in stroke mortality exhibits heterogeneity by stroke type, remains uncertain., Methods: We undertook a sequential time series analysis to examine stroke mortality trends in the USA among people aged 18-84 years between 1975 and 2019 (n = 4 332 220). Trends were examined for overall stroke and by ischaemic and haemorrhagic subtypes. Mortality data were extracted from the US death files, and age-sex population data were extracted from US census. Age-standardized stroke mortality rates and incidence rate ratio (IRR) with 95% confidence interval [CI] were derived from Poisson regression models., Results: Age-standardized stroke mortality declined for females from 87.5 in 1975 to 30.9 per 100 000 in 2019 (IRR 0.27, 95% CI 0.26, 0.27; average annual decline -2.78%, 95% CI -2.79, -2.78). Among males, age-standardized mortality rate declined from 112.1 in 1975 to 38.7 per 100 000 in 2019 (RR 0.26, 95% CI 0.26, 0.27; average annual decline -2.80%, 95% CI -2.81, -2.79). Stroke mortality increased sharply with advancing age. Decline in stroke mortality was steeper for ischaemic than haemorrhagic strokes., Conclusions: Stroke mortality rates have substantially declined, more so for ischaemic than haemorrhagic strokes., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background In 1998, President Clinton launched a federal initiative to eliminate racial and ethnic health disparities. The impact on the outcomes of ST-segment-elevation myocardial infarction has not been well studied. Methods and Results ST-segment-elevation myocardial infarction outcomes from 1994 to 2015 were studied in 7942 Black, 27 665 Hispanic, and 88 727 White patients with first admission of ST-segment-elevation myocardial infarction using the Myocardial Infarction Data Acquisition System. Logistic regressions were used to assess mortality adjusting for demographics, comorbidities, and interventional procedures. There was an overall rise from 1994 to 2015 in the use of percutaneous coronary interventions in all 3 groups. Before 1998, White patients received more percutaneous coronary interventions compared with Black and Hispanic patients ( P <0.05). After 1998, the disparity in use of percutaneous coronary interventions in Black and Hispanic patients was greatly reduced compared with White patients, and the difference reversed in favor of Hispanic patients after 2005 ( P <0.05). There was an overall downward trend of in-hospital mortality without evidence of disparity among Black, Hispanic, and White patients. A linear regression model was used with a change point in 1998. Before 1998, the slope of 1-year all-cause and cardiovascular mortality was not statistically significant. After 1998, the mortality showed negative slopes for all 3 groups, however, with lower overall crude mortality for Hispanic patients compared with Black and White patients ( P <0.0001). Conclusions The initiative launched in 1998 may have contributed to a reduction in percutaneous coronary intervention usage disparity in patients with ST-segment-elevation myocardial infarction. Short- and long-term mortality decreased in all 3 groups, but more in the Hispanic population.

Background: Accumulating evidence from clinical trials suggests that a lower (restrictive) hemoglobin threshold (<8 g/dL) for red blood cell (RBC) transfusion, compared with a higher (liberal) threshold (≥10 g/dL) is safe. However, in anemic patients with acute myocardial infarction (MI), maintaining a higher hemoglobin level may increase oxygen delivery to vulnerable myocardium resulting in improved clinical outcomes. Conversely, RBC transfusion may result in increased blood viscosity, vascular inflammation, and reduction in available nitric oxide resulting in worse clinical outcomes. We hypothesize that a liberal transfusion strategy would improve clinical outcomes as compared to a more restrictive strategy., Methods: We will enroll 3500 patients with acute MI (type 1, 2, 4b or 4c) as defined by the Third Universal Definition of MI and a hemoglobin <10 g/dL at 144 centers in the United States, Canada, France, Brazil, New Zealand, and Australia. We randomly assign trial participants to a liberal or restrictive transfusion strategy. Participants assigned to the liberal strategy receive transfusion of RBCs sufficient to raise their hemoglobin to at least 10 g/dL. Participants assigned to the restrictive strategy are permitted to receive transfusion of RBCs if the hemoglobin falls below 8 g/dL or for persistent angina despite medical therapy. We will contact each participant at 30 days to assess clinical outcomes and at 180 days to ascertain vital status. The primary end point is a composite of all-cause death or recurrent MI through 30 days following randomization. Secondary end points include all-cause mortality at 30 days, recurrent adjudicated MI, and the composite outcome of all-cause mortality, nonfatal recurrent MI, ischemia driven unscheduled coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), or readmission to the hospital for ischemic cardiac diagnosis within 30 days. The trial will assess multiple tertiary end points., Conclusions: The MINT trial will inform RBC transfusion practice in patients with acute MI., Competing Interests: Disclosures JLC: DSMB member for Cerus Corporation project. MMB: DSMB member for Cerus Corporation project. JDA: Research funding MicroPort, Boston Scientific. Advisory Boards Philips, Medtronic. Consulting Abbott, Shockwave, Penumbra, Recor. SGG: Research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from: Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, Valeo Pharma; and salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, TIMI Study Group (Brigham Health). AMG: None. MHB: None. Philippe Gabriel Steg: has received research grants from Bayer, Merck, Sanofi, Servier; has been a speaker or consultant for Amarin, Amgen, AstraZeneca, Bayer, Bristol-Myers-Squibb, Janssen, Lexicon, Merck, Novartis, Novo-Nordisk, PhaseBio, Pfizer, Regeneron, Sanofi, Servier. He is a Senior Associate Editor for Circulation. APD: Consultant Velakor Biotherapeutics Inc. RDL: Grants from Bristol-Myers Squibb, GlaxoSmithKline plc., Medtronic, Pfizer, Bayer, Sanofi; consulting fees from Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Novo Nordisk, GlaxoSmithKline plc., Medtronic, Merck, Pfizer, Portola, Sanofi; and honoraria for lectures from Bristol-Myers Squibb, Pfizer, Daiichi Sankyo, Novo Nordisk, and Bayer. PCH: DSMB member of Cerus Corporation project., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cardiovascular (CV) disease accounts for 1/3 of deaths worldwide and 1/4 of deaths nationwide. Socioeconomic status (SES) affects CV health and outcomes. Previous studies that examined the association of SES and CV outcomes have yielded mixed results. Using a large-scale database, the aim of this study was to assess the magnitude of the association between categorized median household income, an indicator for SES, and nonfatal or fatal acute myocardial infarction (AMI). Using logistic regression models, zip code median household income data from the United States Census Bureau were matched to 1-year rates of hospital readmission for AMI and CV death. Patient outcomes were obtained from the Myocardial Infarction Data Acquisition System, a comprehensive database that includes all patient CV disease admissions to acute care New Jersey hospitals. Our main results indicate that compared with those in the highest household income level (>$68,000), patients in the lowest-income group (<$43,000) had significantly higher risk for AMI readmission (adjusted odds ratio 1.1388, 95% confidence interval 1.0905 to 1.1893, p = 0) and CV death (odds ratio 1.0479, 95% confidence interval 1.0058 to 1.0917, p = 0.0254) after 1 year. This study also found that the likelihood of AMI readmission increased as household income levels decreased. Our findings suggest that healthcare professionals and policy makers should allocate additional resources to low-income communities to reduce disparities in AMI hospital readmissions and AMI case fatalities., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate the necessity of cardiac testing after a COVID-19 diagnosis as it relates to myocarditis in collegiate athletes., Design: Cross-sectional retrospective case series., Setting: National Collegiate Athletic Association Division I University., Patients: One hundred sixty-five collegiate athletes diagnosed with COVID-19 by reverse transcriptase-polymerase chain reaction or immunoglobulin G antibody between August and December 2020 without exclusion., Interventions: All participants underwent cardiac workup consisting of serum troponin, electrocardiogram, transthoracic echocardiogram, and cardiac magnetic resonance (CMR). All results were reviewed by team physicians and sports cardiologists., Main Outcome Measures: Prevalence of myocarditis and abnormality on cardiac testing after COVID-19 infection at a single institution., Results: One (0.61% [95% CI, 0.02%-3.3%] asymptomatic athlete had CMR findings of an age-indeterminate myocardial injury with further cardiac testing being otherwise normal. No athlete had CMR abnormalities consistent with acute myocarditis by the modified Lake Louise Criteria., Conclusions: Occurrence of myocarditis was lower in this population compared with other studies. No student athlete was permanently disqualified from participation because of testing. A stratified, risk-based testing strategy with CMR may be more appropriate than a universal screening strategy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Physical activity and exercise after stroke is strongly recommended, providing many positive influences on function and secondary stroke prevention. The purpose of this study was to investigate the effect of a stroke recovery program (SRP) integrating modified cardiac rehabilitation on mortality and functional outcomes for stroke survivors., Methods: This study used a retrospective analysis of data from a prospectively collected stroke rehabilitation database which followed 449 acute stroke survivors discharged from an inpatient rehabilitation facility between 2015 and 2020. For 1-year post-stroke, 246 SRP-participants and 203 nonparticipants were compared. The association of the SRP including modified cardiac rehabilitation with all-cause mortality and functional performance was assessed using the following statistical techniques: log rank test, Cox proportional hazard model and linear mixed effect models. Cardiovascular performance over 36 sessions of modified cardiac rehabilitation was assessed using linear effect model with Tukey procedure. The primary outcome measure was 1-year all-cause mortality rate. Secondary outcomes were functional performance measured in Activity Measure of Post-Acute Care scores and cardiovascular performance measured in metabolic equivalent of tasks times minutes., Results: The SRP-participants had: (1) a significantly reduced 1-year post-stroke mortality rate from hospital admission corresponding to a four-fold reduction in mortality (P = 0.005, CI for risk ratio = [0.08, 0.71]), (2) statistically and clinically significant improvement of function in all Activity Measure of Post-Acute Care domains (P < 0.001 for all, 95% CI for differences in Basic Mobility [5.9, 10.1], Daily Activity [6.2, 11.8], and Applied Cognitive [3.0, 6.8]) compared to the matched cohort and (3) an improvement in cardiovascular performance over 36 sessions with an increase of 78% metabolic equivalent of tasks times minutes (P < 0.001, 95% CI [70.6, 85.9%]) compared to baseline., Conclusions: Stroke survivors who participated in a comprehensive stroke recovery program incorporating modified cardiac rehabilitation had decreased all-cause mortality, improved overall function, and improved cardiovascular performance., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

Background: Patients diagnosed with atrial fibrillation (AF) are at increased risk of stroke. Several guidelines to assess the risk of ischemic stroke and major bleeding in AF patients have been published. The CHA 2 DS 2 -VASc score has been adopted widely for predicting stroke within one year of the index AF diagnosis and is used to guide the prescription of anticoagulants. Anticoagulation therapy increases the risk of bleeding and scoring systems such as HAS-BLED assess the risk of major bleeding in anticoagulated patients. Despite these advances, no study has examined the risks of the two outcomes simultaneously. How patients' fear of particular outcomes affects these risks also remains unknown., Methods: We incorporated the risks of ischemic stroke and major bleeding within one year of the index AF admission as well as the fear of stroke and bleeding of each individual patient. The patients enrolled in this retrospective observational study were identified using hospital admission data from the Myocardial Infarction Data Acquisition System (MIDAS), a statewide database including all hospitalizations for cardiovascular disease in New Jersey. Probabilities of the outcomes (ischemic stroke, major bleeding, both, or neither within one year of the index AF admission) were estimated using multinomial regression with patient demographics and comorbidities (heart failure [HF], hypertension [HTN], diabetes mellitus [DM], anemia, chronic obstructive pulmonary disease [COPD], kidney disease [KD], prior stroke or transient ischemic attack [TIA]) as predictors. These estimates were used in a Deming regression to model the association of ischemic stroke and major bleeding in grouped patients. The assessment of the importance of each outcome was superimposed on the final model to arrive at a recommendation for anticoagulation therapy., Results: The results of the Deming regression indicated a positive relationship between ischemic stroke and major bleeding (slope = 1.67, 95% confidence interval [CI] 1.37 to 1.97). Estimates of the risks of the two outcomes and the lines of best fit from Deming regression were determined. This model for risk assessment of stroke and major bleeding within one year of the index AF hospital admission combined objective data and subjective assessment of the relative fear of stroke versus bleeding by each hypothetical patient on 0-100 scale. Examples with the fears of stroke versus major bleeding being equal (50-50) and a higher fear of stroke (80-20) are presented., Conclusions: The new model for risk assessment of ischemic stroke and major bleeding within one year of the index AF hospital admission proposed in this work used objective, empirically driven measures, and subjective assessment of the outcomes' importance for individual patients. Such models may assist physicians in their decision making regarding anticoagulation therapy., Competing Interests: All authors declare: no support from any organization for the submitted work; no financial relationships with any organizadutions that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work., (© 2022 The Authors. Published by Elsevier B.V.)

Objective: A Stroke Recovery Program (SRP) including cardiac rehabilitation demonstrated lower all-cause mortality rates, improved cardiovascular function, and overall functional ability among stroke survivors. Neither an effect of SRP on acute care hospital readmission rates nor cost savings have been reported., Design: This prospective matched cohort study included 193 acute stroke survivors admitted to an inpatient rehabilitation facility between 2015 and 2017. The 105 SRP participants and 88 nonparticipants were matched exactly for stroke type, sex, and race and approximately for age, baseline functional scores, and medical complexity scores. Primary outcome measured acute care hospital readmission rate up to 1 yr post-stroke. Secondary outcomes measured costs., Results: A 22% absolute reduction (P = 0.006) in hospital readmissions was observed between the SRP participant (n = 47, or 45%) and nonparticipant (n = 59, or 67%) groups. This resulted in significant cost savings. The conventional care cost to the Center for Medicare and Medicaid Services for stroke patients for both readmissions and outpatient therapy is estimated at $9.67 billion annually. The yearly cost for these services with utilization of the SRP is $8.55 billion., Conclusion: Acute care hospital readmissions were reduced in stroke survivors who participated in SRP. Future study is warranted to examine whether widespread application of a similar program may improve quality of life and decrease cost., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Placental abruption and cardiovascular disease (CVD) have common etiological underpinnings, and there is accumulating evidence that abruption may be associated with future CVD. We estimated associations between abruption and coronary heart disease (CHD) and stroke. The meta-analysis was based on the random-effects risk ratio (RR) and 95% confidence interval (CI) as the effect measure. We conducted a bias analysis to account for abruption misclassification, selection bias, and unmeasured confounding. We included 11 cohort studies comprising 6,325,152 pregnancies, 69,759 abruptions, and 49,265 CHD and stroke cases (1967-2016). Risks of combined CVD morbidity-mortality among abruption and nonabruption groups were 16.7 and 9.3 per 1,000 births, respectively (RR = 1.76, 95% CI: 1.24, 2.50; I2 = 94%; τ2 = 0.22). Women who suffered abruption were at 2.65-fold (95% CI: 1.55, 4.54; I2 = 85%; τ2 = 0.36) higher risk of death related to CHD/stroke than nonfatal CHD/stroke complications (RR = 1.32, 95% CI: 0.91, 1.92; I2 = 93%; τ2 = 0.15). Abruption was associated with higher mortality from CHD (RR = 2.64, 95% CI: 1.57, 4.44; I2 = 76%; τ2 = 0.31) than stroke (RR = 1.70, 95% CI: 1.19, 2.42; I2 = 40%; τ2 = 0.05). Corrections for the aforementioned biases increased these estimates. Women with pregnancies complicated by placental abruption may benefit from postpartum screening or therapeutic interventions to help mitigate CVD risks., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Arterial stiffness is important because it is associated with adverse cardiovascular events including stroke. Methods that are based on pulse wave velocity have significant limitations in estimating arterial stiffness. The purpose of this paper is to present a novel easy to apply non-invasive method to estimate arterial stiffness that is based on pulse pressure., Methods: Two indices to estimate arterial stiffness, (1) arterial stiffness 1 (AS1) and (2) arterial stiffness 2 (AS2) were developed and applied in two National Institutes of Health funded clinical trials, the Systolic Hypertension in the Elderly Program and the Systolic Blood Pressure Intervention Trial. These indices were developed by fitting individual survival models for selected predictor variables to the response, i.e. time to stroke, by selecting the coefficients that were statistically significant at the 0.05 α level after adjusting the variable weights. The indices were derived as the weighted linear combination of the coefficients., Results: AS1 and AS2 performed well in two goodness of fit criteria i.e. overall model p-value and concordance correlation. Comparison of Cox models using indices AS1 and AS2 and chronological age indicated that AS1 and AS2 independently predicted the occurrence of stroke at five years better than chronological age. Nearly identical effects were observed when the analyses were limited to Black participants in SPRINT with a concordance correlation of 0.80 and log rank test p-value of 0.007., Conclusion: These indices that are derived from pulse pressure predict the occurrence of stroke better than either pulse pressure or chronological age alone and may be used in designing new randomized clinical trials, and possibly incorporated in hypertension and stroke guidelines., Competing Interests: We state that this manuscript is not under consideration elsewhere and that the research reported will not be submitted for publication elsewhere until a final decision is made as to the acceptability of the manuscript. There is no financial or other relationship that influenced the outcome of this paper. In addition, this manuscript represents original work without fabrication, fraud, plagiarism and has been read and approved by all authors., (© 2021 The Authors.)

We investigated the incidence and characteristics of 14,996 patients with aortic stenosis (AS) who were hospitalized in New Jersey between the years 1995 to 2015. The average age was 72, the majority were Caucasian males and common co-morbidities were hypertension, coronary artery disease and hypercholesterolemia. Hospital admission for AS declined between 1995 to 2007, to 10/100,000 patients, and increased to 15/100,000 patients in 2015 (p for trend <0.001). During the study period, the percentage of patients who received aortic valve replacement (AVR) increased (p <0.001). All-cause and cardiovascular mortality were higher among patients who did not undergo AVR at 1-year (HR 1.98 CI 1.75 to 2.23, p <0.001 and HR 1.82 CI 1.57 to 2.11, p <0.001, respectively) and 3-years (HR 2.16 CI 1.96 to 2.38, p <0.001 and HR 2.16 CI 1.90 to 2.45, p <0.001, respectively). The probability for readmission for AS was higher in patients who did not receive AVR compared to patients who had AVR at 1 year (HR 92.95 CI 57.85 to 149.35, p <0.001) and 3 years (HR 70.36 CI 47.18 to 104.95, p <0.001). These data imply that earlier diagnosis of AS and AVR when indicated will improve outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) examined the performance of chlorthalidone (C) versus amlodipine (A) monotherapies. ANOVA was used to analyze the differences in systolic blood pressure (SBP) response between C and A. Logistic regression was used to examine monotherapy failure (adding a second antihypertensive agent or switching to a different antihypertensive agent) rates. Four hundred ninety-one participants were treated with C monotherapy (n = 210, mean dose = 22 mg/day) or A monotherapy (n = 281, mean dose = 7 mg/day). There was a significant difference in mean SBP reduction between the C and A monotherapies at the third visit (higher reduction with A, adjusted p = .018). Unadjusted analysis showed a higher failure with C in the standard treatment group. Although the average SBP at failure was higher and above the 140 mm Hg cutoff that indicated monotherapy failure with A (142.60) compared with C (138.40), more participants on C failed despite having SBP below the 140 cutoff. This was probably due to decisions made by the investigative teams to change the antihypertensive regimen, because, in their opinion, the clinical picture required it. After adjusting for baseline characteristics, C had higher failure than A only in the standard treatment group (1.64 odds ratio [OR], 95% CI 1.06-2.56, p = .028). A sub-analysis including participants who had never used antihypertensive treatment before randomization had similar results (2.57 OR, 95% CI 1.34-5.02, p = .004). Overall, in SPRINT chlorthalidone was associated with higher monotherapy failure than amlodipine in the standard treatment group because of decisions of the investigative teams., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Constrictive pericarditis is a rare complication of open heart surgery (OHS), but little is known regarding the etiologic determinants, and prognostic factors. The purpose of this study was to investigate clinical predictors and long term prognosis of post-operative constrictive pericarditis (CP)., Methods: Using the Myocardial Infarction Data Acquisition System database, we analyzed records of 142,837 patients who were admitted for OHS in New Jersey hospitals between 1995 and 2015. Ninety-one patients were hospitalized with CP 30 days or longer after discharge from OHS. Differences in proportions were analyzed using Chi square tests. Controls were matched to cases for demographics, surgical procedure type, history of OHS, and propensity score. Cox proportional hazard models were used to evaluate the risk of all-cause death. Log-rank tests and Cox models were used to assess differences in the Kaplan-Meier survival curves with and without adjustments for comorbidities., Results: Patients with CP were more likely to have history of valve disease (VD, p < 0.001), atrial fibrillation (AF, p = 0.024) renal disease (CKD, p = 0.028), hemodialysis (HD, p = 0.008), previous OHS (p < 0.001). Patients with CP compared to matched controls had a higher 7-year mortality (p < 0.001). This difference became statistically significant at 1-year after surgery., Conclusion: CP is a rare complication of OHS that occurs more frequently in patients with VD, AF, CKD, HD, multiple OHS, and it is associated with an unfavorable long-term prognosis. Given the large number of OHS performed every year, the results highlight the need for clinicians to recognize and properly manage this complication of OHS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Although many predictive models have been developed to risk assess medical intensive care unit (MICU) readmissions, they tend to be cumbersome with complex calculations that are not efficient for a clinician planning a MICU discharge., Objective: To develop a simple scoring tool that comprehensively takes into account not only patient factors but also system and process factors in a single model to predict MICU readmissions., Design: Retrospective chart review., Participants: We included all patients admitted to the MICU of Robert Wood Johnson University Hospital, a tertiary care center, between June 2016 and May 2017 except those who were < 18 years of age, pregnant, or planned for hospice care at discharge., Main Measures: Logistic regression models and a scoring tool for MICU readmissions were developed on a training set of 409 patients, and validated in an independent set of 474 patients., Key Results: Readmission rate in the training and validation sets were 8.8% and 9.1% respectively. The scoring tool derived from the training dataset included the following variables: MICU admission diagnosis of sepsis, intubation during MICU stay, duration of mechanical ventilation, tracheostomy during MICU stay, non-emergency department admission source to MICU, weekend MICU discharge, and length of stay in the MICU. The area under the curve of the scoring tool on the validation dataset was 0.76 (95% CI, 0.68-0.84), and the model fit the data well (Hosmer-Lemeshow p = 0.644). Readmission rate was 3.95% among cases in the lowest scoring range and 50% in the highest scoring range., Conclusion: We developed a simple seven-variable scoring tool that can be used by clinicians at MICU discharge to efficiently assess a patient's risk of MICU readmission. Additionally, this is one of the first studies to show an association between MICU admission diagnosis of sepsis and MICU readmissions.

Purpose: There has been considerable debate on the extent to which the decline in coronary heart disease (CHD) mortality has been caused by better control of coronary risk factors in the general population or is the result of invasive coronary interventions in symptomatic individuals., Methods: Using the Myocardial Infarction Data Acquisition System, a statewide database of all cardiovascular hospital admissions in New Jersey, we examined time trends in incidence of death from CHD in the Years 2000-2014 in persons with a history of hospitalization for CHD in the previous 10 years and those without such a history., Results: Over the 10-year study period, there was a marked decline in CHD-related mortality in both persons with a history of CHD and persons without a history of CHD. The decline occurred across all gender, racial, and age groups and was higher in those without a prior history of CHD., Conclusions: This adds more evidence that the decline in CHD was not only because of advanced invasive medical and surgical treatments but also equally because of improved lifestyle, pharmacologic treatment of risk factors for CHD, and public health interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: This study assessed the accuracy of an algorithm that predicts the origin of focal arrhythmias using a limited number of data points., Background: Despite advances in technology, ablations can be time-consuming, and activation mapping continues to have inherent limitations. The authors developed an algorithm that can predict the origin of a focal wavefront using the location and activation timing information in 2 pairs of sampled points. This algorithm was incorporated into an electroanatomic mapping (EAM) system to assess its accuracy in a 3-dimensional clinical environment., Methods: EAM data from patients who underwent successful ablation of a focal wavefront using the CARTO3 system were loaded onto an offline version of the software modified to contain the algorithm. Prediction curves were retrospectively generated. Predictive accuracy, defined as the distance between true and predicted origin wavefront origins, was measured., Results: Seventeen wavefronts in as many patients (2 with atrial tachycardia, 3 with orthodromic re-entrant tachycardia, 8 with premature ventricular complex and/or ventricular tachycardia, 4 with focal pulmonary vein isolation breakthroughs) were studied. Thirty-three origin predictions were attempted (1.9 ± 0.4 per patient) using 132 points. Predictions were successfully calculated in 31 of 33 (93.9%) attempts and were accurate to within 5.7 ± 6.9 mm. Individual prediction curves were accurate to within 3.0 ± 4.7 mm., Conclusions: Focal wavefront origins may be accurately predicted in 3 dimensions using a novel algorithm incorporated into an EAM system., Competing Interests: Author Relationship With Industry This work was supported by research funding from Biosense Webster. Dr. Saluja is a patent holder (through Rutgers University) of the background technology used in this research. Mr. Bar-on and Mr. Hayam are employees of Biosense Webster. Dr. Coromilas has been a consultant for DRF and Abbott; and has been a member of the Clinic Events Committee for Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: The most feared complication of pulmonary vein isolation (PVI) is an atrioesophageal fistula (AEF). While rare (0.1-0.25%), primary surgical closure (as opposed to esophageal stenting) is associated with lower mortality. Pericardioesophageal fistula (PEF) may present prior to fistulization into the atrium. Unfortunately, data on the optimal management of PEFs are lacking., Case Report: Seventy-one-year-old male with AF presented with chest pain 3 weeks after radiofrequency PVI. Computed tomography angiography (CTA) chest and echocardiogram showed pneumopericardium. Barium esophagram showed extravasation from esophagus into the pericardium without connection to the left atrium. Sternotomy with mediastinal exploration exposed the pericardial defect, over which a CorMatrix patch was placed. The fistula was then stented endoscopically with endosuture fixation. Poststent esophagram did not show barium leak, and the patient was discharged home. One week later, the patient returned with enterococcal and candida bacteremia and an acute right parietal/occipital lobe infarct. Barium esophagram showed contrast extravasation into the pericardium. The patient rapidly succumbed to his illness and died. Autopsy revealed pericardial abscess posterior to the LA in communication with the esophagus. Extension to the LA was not seen., Conclusion: While the surgical treatment of AEF is relatively well established, there is no consensus in the management of PEF. While prior small series have suggested PEF may be managed with esophageal stenting, our case illustrates the limitations of this approach., (© 2020 Wiley Periodicals LLC.)

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) was conducted in patients with hypertension and additional risk for cardiovascular disease who were randomized to the intensive blood pressure group targeting systolic blood pressure (SBP) less than 120 mm Hg and to the standard group where the target was less than 140 mm Hg. Analyses were done in the matched group of participants with the same gender, same age (±2 years) and same SBP (±3 mm Hg) at three months of treatment regardless of initial randomization to intensive or standard group (shaded area in Figure 1)., Methods and Results: During 3.26 years of follow-up, intensive group participants had 14.8 mm Hg lower SBP and received on average one more (2.8 vs. 1.8) blood pressure lowering medications. This was associated with lower all-cause mortality in the intensive treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90, p = 0.003). The effect on SBP was achieved at 3 months and remained unchanged thereafter. This paper addresses two questions with respect to all-cause mortality in SPRINT in the matched set. 1) What is the effect of receiving more than one drug on all-cause mortality. Conditional logistic regression for all-cause mortality with respect to number of drugs indicated that during the 3.26 years of follow-up persons who received more than one drug were more likely to die (coefficient = 0.5039, OR = 1.6552, p = 0.0322) than patients who received one drug. 2) Was there a U curve relationship between on treatment SBP and all-cause mortality? A U curve fitting a quadratic equation (parabola) of SBP and all-cause death was observed. This was seen in the patients randomized to the standard target group in unadjusted analyses as well as in analyses adjusted for demographics or all covariates (p < 0.001 for all). The U curves in the combined group and the intensive treatment group were less pronounced., Conclusion: SPRINT participants who were matched for gender, age, and SBP at 3 months, and received more than one drug had higher all-cause mortality during the 3.26 years of follow-up. Those who were randomized to standard treatment target had a U curve relationship between SBP at three months and all-cause mortality. The U curves in the combined group and the intensive treatment group were less pronounced., Competing Interests: The authors declare that they have no competing interests., (© 2020 The Authors.)

There is a paucity of data comparing irrigated to non-irrigated catheters in the ablation of accessory pathways (AP) in adult patients. Retrospective analysis of first-time AP ablations performed at our institution from May 2010 to June 2017. A total of 69 AP ablations were studied; irrigated catheters were used in 78.3% cases. Mean age was 40.9 ± 14.3 years and 56.7% were male. Among APs, 63.8% were left sided and 56.5% were concealed. The total procedure time was 232.0 ± 89.0 min, ablation time was 3.1 ± 5.1 min, and fluoroscopy time was 13.9 ± 15.4 min. The overall acute success rate of ablation was 62/69 (89%). Success rates trended higher with irrigated catheters in both groups and were significant for the population as a whole (94.4% vs. 73.3%, p = 0.04). Analyzing the entire cohort, success rates were significantly higher in ablations using irrigated catheters.

Background: The duration of randomized controlled clinical trials usually is approximately 3 to 5 years although hypercholesterolemia and other risk factors for atherosclerotic cardiovascular disease (ASCVD) are lifelong conditions., Objectives: The legacy effect, defined as the persistence of benefit of pharmacologic interventions in clinical trials after the end of the randomized phase when all participants receive active therapy, is used to examine the long-term benefit. We summarize the evidence for the existence of the legacy effect as it pertains to hypercholesterolemia, describe underlying mechanisms, and discuss its relevance to clinical practice., Methods: We examined all published (n = 13) randomized clinical trials of lipid-lowering agents compared to placebo or usual care with follow-up after the randomized phase for the presence or absence of a legacy effect., Results: A legacy effect was demonstrated in all studies. The current US and European guidelines recommend treatment with high-intensity statins for patients with manifest ASCVD and that individualized approach be used for primary prevention., Conclusion: The legacy effect results in significant long-term clinical benefits by preventing fatal and nonfatal events. This implies that early therapy would result in lower event rates. Long-term follow-up should be a part of clinical trial design in order to evaluate the presence or absence of a legacy effect.

Objective was to examine the temporal trends in readmission and mortality of heart failure (HF) patients with history of hypertension. This study includes 51 141 patients with history of hypertension who were discharged with a first diagnosis of HF between January 1, 2000, and December 31, 2014. Data were obtained from the Myocardial Infarction Data Acquisition System (MIDAS), a statewide database of all hospitalizations for cardiovascular (CV) disease in New Jersey. The temporal trends of mortality, rates of HF-specific readmission, and all-cause readmissions up to 1 year after discharge were examined using multivariable logistic regression. The difference in all-cause mortality at 3 years between patients who were readmitted compared to those who were not readmitted at 1 year was examined. The number of patients with history of hypertension and HF remained unchanged during the study period. Male gender, black race, comorbidities, and admission to non-teaching hospitals were predictors of HF readmission and CV mortality (P < .05 for all). Readmission rate for any cause increased during the study period (P < .001) while rates of HF readmissions and mortality remained relatively unchanged. Patients that had been readmitted within a year exhibited a significantly higher 3-year mortality (P < .001). CV mortality among HF patients with history of hypertension did not change significantly between 2000 and 2014, while the rates of all-cause readmission increased. Patients who were readmitted had higher 3-year mortality (P < .001) than those who were not., (© 2020 Wiley Periodicals LLC.)

Clinical guidelines from the United States and Europe do not recommend treatment with statins for primary prevention in patients with hypercholesterolemia who are older than 75 years. Data from 35 randomized controlled trials in this age group where statin therapy for primary prevention was compared with placebo or usual care were analyzed. Using all-cause death as the outcome, we performed 2 types of analyses: frequentist and Bayesian. Frequentist analysis indicated no significant difference in mortality between cases (on statins) and controls (on placebo or usual care, p = 0.16). However, in the Bayesian analysis, patients >75 years had lower mortality from treatment with statins (p = 0.03). In conclusion, Bayesian analysis indicates a definite, statistically significant and clinically relevant benefit of statin treatment for primary prevention in patients >75 years of age., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Artificial intelligence (AI) promises to provide useful information to clinicians specializing in hypertension. Already, there are some significant AI applications on large validated data sets., Methods and Results: This review presents the use of AI to predict clinical outcomes in big data i.e. data with high volume, variety, veracity, velocity and value. Four examples are included in this review. In the first example, deep learning and support vector machine (SVM) predicted the occurrence of cardiovascular events with 56%-57% accuracy. In the second example, in a data base of 378,256 patients, a neural network algorithm predicted the occurrence of cardiovascular events during 10 year follow up with sensitivity (68%) and specificity (71%). In the third example, a machine learning algorithm classified 1,504,437 patients on the presence or absence of hypertension with 51% sensitivity, 99% specificity and area under the curve 87%. In example four, wearable biosensors and portable devices were used in assessing a person's risk of developing hypertension using photoplethysmography to separate persons who were at risk of developing hypertension with sensitivity higher than 80% and positive predictive value higher than 90%. The results of the above studies were adjusted for demographics and the traditional risk factors for atherosclerotic disease., Conclusion: These examples describe the use of artificial intelligence methods in the field of hypertension., Competing Interests: The authors declare that they have no competing interests., (© 2020 The Authors.)

Purpose: Pulmonary vein isolation (PVI) for atrial fibrillation has been shown to result in inexcitability of a large fraction of pulmonary veins (PVs), but the mechanism is unknown. We investigated the mechanism of PV inexcitability by assessing the effects of PVI on the electrophysiology of PV sleeves., Methods: Patients undergoing first-time radiofrequency PVI were studied. Capture threshold, effective refractory period (ERP), and excitability were measured in PVs and the left atrial appendage (LAA) before and after ablation. Adenosine was used to assess both transient reconnection and transient venous re-excitability., Results: We assessed 248 veins among 67 patients. Mean PV ERP (249.7 ± 54.0 ms) and capture threshold (1.4 ± 1.6 mA) increased to 300.5 ± 67.1 and 5.7 ± 5.6 mA, respectively (P < .0001 for both) in the 26.9% PVs that remained excitable, but no change was noted in either measure in the LAA. In 16.3% of the 73.1% inexcitable veins, transient PV re-excitability (as opposed to reconnection) was seen with adenosine administration., Conclusions: Antral PVI causes inexcitability in a majority of the PVs, which can transiently be restored in some with adenosine. Among PVs that remain excitable, ERP and capture threshold increase significantly. These data imply resting membrane potential depolarization of the of PV myocardial sleeves. As PV inexcitability hampers the assessment of entrance and exit block, demonstrating transient PV re-excitability during adenosine administration helps ensure true isolation., (© 2019 Wiley Periodicals, Inc.)

The SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated reduced cardiovascular outcomes. We evaluated diabetes mellitus incidence in this randomized trial that compared intensive blood pressure strategy (systolic blood pressure <120 mm Hg) versus standard strategy (<140 mm Hg). Participants were ≥50 years of age, with systolic 130 to 180 mm Hg and increased cardiovascular risk. Participants were excluded if they had diabetes mellitus, polycystic kidney disease, proteinuria >1 g/d, heart failure, dementia, or stroke. Postrandomization exclusions included participants missing blood glucose or ≥126 mg/dL (6.99 mmol/L) or on hypoglycemics. The outcome was incident diabetes mellitus: fasting blood glucose ≥126 mg/dL (6.99 mmol/L), diabetes mellitus self-report, or new use of hypoglycemics. The secondary outcome was impaired fasting glucose (100-125 mg/dL [5.55-6.94 mmol/L]) among those with normoglycemia (<100 mg/dL [5.55 mmol/L]). There were 9361 participants randomized and 981 excluded, yielding 4187 and 4193 participants assigned to intensive and standard strategies. There were 299 incident diabetes mellitus events (2.3% per year) for intensive and 251 events (1.9% per year) for standard, rates of 22.6 (20.2-25.3) versus 19.0 (16.8-21.5) events per 1000 person-years of treatment, respectively (adjusted hazard ratio, 1.19 [95% CI, 0.95-1.49]). Impaired fasting glucose rates were 26.4 (24.9-28.0) and 22.5 (21.1-24.1) per 100 person-years for intensive and standard strategies (adjusted hazard ratio, 1.17 [1.06-1.30]). Intensive treatment strategy was not associated with increased diabetes mellitus but was associated with more impaired fasting glucose. The risks and benefits of intensive blood pressure targets should be factored into individualized patient treatment goals. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Objective: Using a feasibility analysis and matched subgroup analysis, this study investigated the implementation/safety/outcomes of a stroke recovery program (SRP) integrating modified cardiac rehabilitation for stroke survivors., Design: This prospective cohort study of 783 stroke survivors were discharged from an inpatient rehabilitation facility to an outpatient setting; 136 SRP-participants completed a feasibility study and received the SRP including modified cardiac rehabilitation, 473 chose standard of care rehabilitation (nonparticipants), and a group (n = 174) were excluded. The feasibility study assessed the following: safety/mortality/pre-post cardiovascular performance/pre-post function/patient/staff perspective. In addition to the feasibility study, a nonrandomized subgroup analysis compared SRP-participants (n = 76) to matched pairs of nonparticipants (n = 66, with 10 nonparticipants used more than once) for mortality/pre-post function., Results: The feasibility study showed the SRP to have the following (a) excellent safety, (b) markedly low 1-yr poststroke mortality from hospital admission (1.47%) compared with national rate of 31%, (c) improved cardiovascular performance over 36 sessions (103% increase in metabolic equivalent of tasks times minutes), (d) improved function in Activity Measure of Post-Acute Care domains (P < 0.001), (e) positive reviews from SRP-participants/staff. Subgroup analysis showed the SRP to (a) positively impact mortality, nonparticipants had a 9.09 times higher hazard of mortality (P = 0.039), and (b) improve function in Activity Measure of Post-Acute Care domains (P < 0.001)., Conclusions: Stroke survivors receiving a SRP integrating modified cardiac rehabilitation may potentially benefit from reductions in all-cause mortality and improvements in cardiovascular performance and function.

We examined the association of orthostatic hypertension with all-cause mortality in the active treatment and placebo randomized groups of the Systolic Hypertension in the Elderly Program (SHEP). SHEP was a multicenter, randomized, double-blind, placebo-controlled clinical trial of the effect of chlorthalidone-based antihypertensive treatment on the rate of occurrence of stroke among older persons with isolated systolic hypertension (ISH). Men and women aged 60 years and above with ISH defined by a systolic blood pressure (SBP) of 160 mm Hg or higher and diastolic blood pressure lower than 90 mm Hg were randomized to chlorthalidone-based stepped care therapy or matching placebo. Among 4736 SHEP participants, 4073 had a normal orthostatic response, 203 had orthostatic hypertension, and 438 had orthostatic hypotension. Compared with normal response, orthostatic hypertension was associated with higher all-cause mortality at 4.5 and 17 years in analyses adjusted for age, gender, treatment, SBP, and pulse pressure (PP, HR 1.87, 95% CI 1.30-2.69, p = 0.0007; HR 1.40, 95% CI 1.17-1.68, p = 0.0003, respectively). These associations remained significant after additional adjustment for risk factors and comorbidities (HR 1.43, 95% CI 0.99-0.08, p = 0.0566 at 4.5 years, and HR 1.27, 95% CI 1.06-1.53, p = 0.0096 at 17 years). The increased risk of all-cause mortality associated with orthostatic hypertension was observed in both the active and placebo groups without significant interaction between randomization group and the effect on mortality. Orthostatic hypertension is associated with future mortality risk, is easily detected, and can be used in refining cardiovascular risk assessment.

Background: Recommendations differ regarding how blood pressure targets should vary with age. Crucial to this controversy is whether treatment benefit varies with age., Methods: Systematic searches were conducted for trials randomizing treatment in intensive arms to the recommended SBP targets: 120-140 mmHg. Head-to-head meta-analyses and meta-regression were conducted., Results: Sixteen trials met criteria. Relative to higher targets, lower targets reduced cardiovascular events, but treatment benefit differed significantly among trials due to patient age. Treatment significantly benefited older patients (mean age 77, SD = 72-81), relative risk (RR) = 0.77 (0.61,0.97), P = 0.025, but not younger patients (mean age 61, SD = 53-70), RR = 0.90 (0.78,1.03), P = 0.121, even though the latter had much greater statistical power. The (RR in 80 year olds)/(RR in 55 year olds) = 0.68 (0.47,0.97), P = 0.036. Though statistically nonsignificant, corresponding trends for more specific outcomes favored older patients: Coronary artery disease 0.80, stroke 0.85, heart failure 0.54, and total mortality 0.76. For adverse effects this trend was 0.86 (0.33,2.26). The number needed to treat to lower targets to prevent one cardiovascular event over 10 years in eight populations declined with age by 94%+., Conclusion: In these novel results, for both RR and absolute risk, treating to SBPs of 120-140 mmHg versus higher targets benefited older patients more than younger patients without an age-related increase in the RR for adverse effects. Nonetheless, because all clinical trials excluded the most frail older patients, clinicians must consider individual patient characteristics such as frailty, autonomy, and cognitive ability when choosing blood pressure targets.

In observational studies, left ventricular mass (LVM) and structure are strong predictors of mortality and cardiovascular events. However, the effect of hypertension treatment on LVM reduction and its relation to subsequent outcomes is unclear, particularly at lower blood pressure (BP) targets. In an ancillary study of SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive BP control (target systolic BP target <120 mm Hg) versus standard BP control (<140 mm Hg), cardiac magnetic resonance imaging was performed at baseline and 18-month follow-up to measure: LVM, volumes, ejection fraction, and native T1 mapping for myocardial fibrosis. At baseline, 337 participants were examined (age: 64±9 years, 45% women); 300 completed the 18-month exam (153 intensive control and 147 standard control). In the intensive versus standard BP control group at 18 months, there was no difference in change in LVM (mean±SE =-2.7±0.5 g versus -2.3±0.7 g; P =0.368), ejection fraction, or native T1 ( P =0.79), but there was a larger decrease in LVM/end-diastolic volume ratio (-0.04±0.01 versus -0.01±0.01; P =0.002) a measure of concentric LV remodeling. There were fewer cardiovascular events in the intensive control group, but no significant association between the reduced events and change in LVM or any other cardiac magnetic resonance imaging measure. In SPRINT-HEART, contrary to our hypothesis, there were no significant between-group differences in LVM, function, or myocardial T1 at 18-month follow-up. These results suggests that mediators other than these LV measures contribute to the improved cardiovascular outcomes with intensive BP control.

We postulate that the trends for infective endocarditis (IE) are different for patients admitted for this condition compared with those admitted for a different reason with IE as a secondary diagnosis. Using the Myocardial Infarction Data Acquisition System (MIDAS) database, we analyzed 21,443 records of patients hospitalized with diagnosis of IE from 1994 to 2015. There were 9,191 patients hospitalized with IE as the primary diagnosis, and 12,252 patients with IE as a secondary diagnosis. Piecewise linear models were used to detect changes in trends. A bootstrap method was used to assess the statistical significance of the slopes and break point of each model. Differences in co-morbidities and microbiological patterns were analyzed. Trend analysis showed a significant decrease in IE as the primary diagnosis starting in the year 2004 (p <0.01). Hospitalizations with IE as a secondary diagnosis showed a linear increase in incidence (p <0.001), without any change points. In primary diagnosis IE, the proportion of streptococci as a causative microorganism was higher compared with staphylococci (p <0.001). On the contrary, in secondary diagnosis IE, the proportion of staphylococci was higher than streptococci (p <0.001). The proportion of gram-negative and other organism IE was similar in both groups. In conclusion, this study showed 2 divergent temporal trends in hospitalizations for IE as a primary or secondary diagnosis starting in 2004. The profile of the microorganisms reveals a steady higher proportion of staphylococcal infection in secondary diagnosis IE compared with streptococcal infection. Different strategies are needed for the prevention of IE., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background Blood pressure ( BP ) varies over time within individual patients and across different BP measurement techniques. The effect of different BP targets on concordance between BP measurements is unknown. The goals of this analysis are to evaluate concordance between (1) clinic and ambulatory BP , (2) clinic visit-to-visit variability and ambulatory BP variability, and (3) first and second ambulatory BP and to evaluate whether different clinic targets affect these relationships. Methods and Results The SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP monitoring ancillary study obtained ambulatory BP readings in 897 participants at the 27-month follow-up visit and obtained a second reading in 203 participants 293±84 days afterward. There was considerable lack of agreement between clinic and daytime ambulatory systolic BP with wide limits of agreement in Bland-Altman plots of -21 to 34 mm Hg in the intensive-treatment group and -26 to 32 mm Hg in the standard-treatment group. Overall, there was poor agreement between clinic visit-to-visit variability and ambulatory BP variability with correlation coefficients for systolic and diastolic BP all <0.16. We observed a high correlation between first and second ambulatory BP ; however, the limits of agreement were wide in both the intensive group (-27 to 21 mm Hg) and the standard group (-23 to 20 mm Hg). Conclusions We found low concordance in BP and BP variability between clinic and ambulatory BP and second ambulatory BP . Results did not differ by treatment arm. These results reinforce the need for multiple BP measurements before clinical decision making.

Healthcare systems may be judged on quality of care and access to health services. Studies on the association of hospital quality of care scores and clinical outcomes have yielded mixed results. With the help of a richer and more representative database, the aim of our study was to shed light on these inconsistencies. We examined the association of 4 process of care scores (prescription of aspirin, β blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker used for left ventricular systolic dysfunction, and an overall composite score) for acute myocardial infarction (AMI), reported in the Hospital Performance Reports, with 30-day and 1-year rates of readmission for AMI and cardiovascular (CV) death. Clinical outcomes were from the Myocardial Infarction Data Acquisition System, an administrative database that comprises all patient CV disease admissions to acute care hospitals in New Jersey. CV death was related with overall score (adjusted odds ratio [OR] 0.821, 95% confidence interval [CI] 0.726 to 0.930, p = 0.002) at 30 days and with all 4 scores at 1 year (OR ranging from 0.829 to 0.997, p <0.01). Readmission due to AMI was associated with the overall score (OR 0.789, 95% CI 0.691 to 0.902, p <0.0001) and the aspirin score (OR 0.995, 95% CI 0.990 to 1, p = 0.046) at 30 days. Low hospital performance scores for AMI were associated with increased CV death and readmission for AMI. In conclusion, healthcare providers should allocate their resources to improving hospital performance to decrease AMI case fatality, AMI readmissions, and CV-related healthcare spending., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Current techniques for mapping and ablating cardiac arrhythmias are valuable, but have limitations. We devised a novel method of predicting the origin of a focal arrhythmia wavefront that utilizes conduction velocity (CV), the difference in electrogram timing during arrhythmia (t), and the distance between two points (z) to generate prediction curves which can be applied to an electroanatomic map. The intersection of two such curves predicts the origin of the wavefront., Objective: To describe the rationale behind a novel method of arrhythmia mapping and assess its feasibility in a retrospective study of focal arrhythmias., Methods: We retrospectively studied 12 patients with arrhythmias with focal chamber activation that were successfully mapped and treated with ablation. CV during arrhythmia was measured using electroanatomic mapping software. Values for z and t were calculated for two pairs of points. Two prediction curves were generated and superimposed onto the electroanatomic maps. The distance between the intersection of the two curves and the wavefront origin was recorded. The shortest distance between individual curves and the wavefront origin was also measured., Results: Twenty-four curves were successfully generated in 12 patients. The distance from the intersection of two curves and the wavefront origin was 9.2 ± 7.7 mm. The shortest distance between individual prediction curves and the wavefront origin was 5.2 ± 5.2 mm., Conclusions: Wavefront origins may be predicted by a novel method utilizing a limited number of measurements. Further study of this method requires its integration with an electroanatomical mapping system., (Copyright © 2018. Published by Elsevier Ltd.)

Patients who develop heart failure (HF) after an acute myocardial infarction (AMI) are at higher risk of adverse fatal and nonfatal outcomes. Published studies on the incidence and associations of HF after infarction have been contradictory, with some reporting increasing and others decreasing incidence. Between 2000 and 2015, 109,717 patients admitted for a first AMI in New Jersey were discharged alive. In the 15 years from 2000 to 2015, the rates of admission for HF in AMI patients who were discharged alive decreased by 60%, from 3.48% to 1.4%, at 1-year follow-up. At 5 years of follow-up, the decline was more pronounced, from 7.21% to 1.4%, an 80% decline. All-cause death, and the combined end point of admission for HF or death, showed decreasing trends. Cox regression indicated a decrease in the risk of admission for HF over time (hazard ratio [HR] 0.955, 95% confidence interval [CI] 0.949 to 0.961). Younger age, male gender, and commercial insurance were associated with lower HRs for HF (p <0.001), whereas history of hypertension, diabetes, kidney, or lung disease were associated with higher HRs (p <0.001). There was no significant difference in the rate of HF between subendocardial and transmural AMI (adjusted OR was 0.96, CI 0.90 to 1.03, p = 0.241). Revascularization was associated with a marked decrease in HF admissions (adjusted OR 0.22, 95% CI 0.19 to 0.25, p <0.001 for percutaneous coronary intervention and OR 0.44, 95% CI 0.38 to 0.51, p <0.001 for CABG). In conclusion, the rate of admission for HF after discharge for a first myocardial infarction as well as all-cause death decreased markedly from 2000 to 2015., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose of Review: This study aims to examine current knowledge on the occurrence, pathophysiology, and treatment of angioedema among patients who receive angiotensin-converting enzyme inhibitors., Recent Findings: Angiotensin-converting enzyme inhibitors (ACE-I), a medication class used by an estimated 40 million people worldwide, are associated with angioedema that occurs with incidence ranging from 0.1 to 0.7%. The widespread use of ACE-I resulted in one third of all emergency department visits for angioedema. Angioedema occurs more frequently in African Americans, smokers, women, older individuals, and those with a history of drug rash, seasonal allergies, and use of immunosuppressive therapy. The pathophysiology of ACE-I-induced angioedema involves inhibition of bradykinin and substance P degradation by ACE (kininase II) leading to vasodilator and plasma extravasation. Treatment modalities include antihistamines, steroids, and epinephrine, as well as endotracheal intubation in cases of airway compromise. Patients with a history of ACE-I-induced angioedema should not be re-challenged with this class of agents, as there is a relatively high risk of recurrence., Conclusion: ACE-I are frequently used therapeutic agents that are associated with angioedema. Their use should be avoided in high-risk individuals and early diagnosis, tracheal intubation in cases of airway compromise, and absolute avoidance of re-challenge are important.

Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 [T1], <132; tertile 2 [T2], 132-145; and tertile 3 [T3], >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction ( P =0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles-a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP., (© 2018 American Heart Association, Inc.)

Background: It is not known whether statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies are associated with cataract and whether very low achieved low-density lipoprotein cholesterol (LDL-C) lowering may cause cataract., Objective: To examine two questions: whether statins and/or PCSK9 antibodies cause or prevent cataracts and whether very low LDL-C is associated with increased risk of cataract., Methods: Systematic searches of PubMed, ClinicalTrials.gov, Web of Science, The Cochrane Library, and an Federal Drug Administration report were used to perform random effects meta-analyses on the relationship of statins and/or PCSK9 antibodies with cataract. These meta-analyses were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Results: Prespecified analyses indicated no significant effect of statins or PCSK9 antibodies (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.83-1.17, P = .8889) or differences between the effects of statins (OR 0.89, 95% CI 0.66-1.19, P = .4349) and PCSK9 antibodies (OR 1.04, 95% CI 0.85-1.28, P = .7042) on the development of cataract. Also, there was no significant effect of LDL-C lowering to different levels with respect to cataract (OR 1.06, 95% CI 0.92-1.22, P = .4317). Meta-regression of the log OR for cataract vs LDL-C during treatment did not show a statistically significant relationship (P for slope = .3972)., Conclusion: There was no significant effect of cholesterol lowering with statins or PCSK9 antibodies or differences between these two medication classes in causing or preventing cataracts. However, it is difficult to make definitive statements regarding PCSK9 antibodies because there is no long-term experience with these agents. Very low LDL-C was not associated with higher risk of cataract., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)