The Association Between Secondhand Smoke Exposure and Survival for Patients With Heart Failure.

BACKGROUND: The effect of secondhand tobacco smoke (SHS) exposure on patients with heart failure (HF) is uncertain. We investigated the association of mortality with SHS exposure for patients with HF. METHODS: Nonsmokers with clinical HF were enrolled from 2003 to 2008 in a single-center longitudinal cohort study. The effect of SHS exposure determined by high-sensitivity urinary cotinine on mortality was estimated by multivariable proportional hazards modeling. RESULTS: Mortality was assessed after median 4.3 years. Of 202 patients, enrollment urinary cotinine levels were below the limit of detection for 106 (52%) considered unexposed to SHS. The median detectable cotinine was 0.47 ng/mL (interquartile range: [0.28, 1.28]). Participants were 41% female, 65 ± 17 years old, and 57% white race. Elevated cotinine was associated with increased mortality after multivariate adjustment: hazard ratio (HR) per 1 ng/mL increase in urinary cotinine: 1.15, 95% confidence interval (CI): 1.08-1.23, P < .001. Higher age (HR per 5-year increase: 1.32, 95% CI: 1.22-1.43, P < .001), male sex (HR vs female: 1.52, 95% CI: 1.02-2.28, P = .040), and New York Heart Association class (HR for class III vs I: 2.91, 95% CI: 1.71-4.99, P < .001) were also associated with mortality. CONCLUSIONS: SHS exposure is associated with a dose-dependent increase in mortality for patients with HF.

Fully Automated Echocardiogram Interpretation in Clinical Practice.

BACKGROUND: Automated cardiac image interpretation has the potential to transform clinical practice in multiple ways, including enabling serial assessment of cardiac function by nonexperts in primary care and rural settings. We hypothesized that advances in computer vision could enable building a fully automated, scalable analysis pipeline for echocardiogram interpretation, including (1) view identification, (2) image segmentation, (3) quantification of structure and function, and (4) disease detection. METHODS: Using 14 035 echocardiograms spanning a 10-year period, we trained and evaluated convolutional neural network models for multiple tasks, including automated identification of 23 viewpoints and segmentation of cardiac chambers across 5 common views. The segmentation output was used to quantify chamber volumes and left ventricular mass, determine ejection fraction, and facilitate automated determination of longitudinal strain through speckle tracking. Results were evaluated through comparison to manual segmentation and measurements from 8666 echocardiograms obtained during the routine clinical workflow. Finally, we developed models to detect 3 diseases: hypertrophic cardiomyopathy, cardiac amyloid, and pulmonary arterial hypertension. RESULTS: Convolutional neural networks accurately identified views (eg, 96% for parasternal long axis), including flagging partially obscured cardiac chambers, and enabled the segmentation of individual cardiac chambers. The resulting cardiac structure measurements agreed with study report values (eg, median absolute deviations of 15% to 17% of observed values for left ventricular mass, left ventricular diastolic volume, and left atrial volume). In terms of function, we computed automated ejection fraction and longitudinal strain measurements (within 2 cohorts), which agreed with commercial software-derived values (for ejection fraction, median absolute deviation=9.7% of observed, N=6407 studies; for strain, median absolute deviation=7.5%, n=419, and 9.0%, n=110) and demonstrated applicability to serial monitoring of patients with breast cancer for trastuzumab cardiotoxicity. Overall, we found automated measurements to be comparable or superior to manual measurements across 11 internal consistency metrics (eg, the correlation of left atrial and ventricular volumes). Finally, we trained convolutional neural networks to detect hypertrophic cardiomyopathy, cardiac amyloidosis, and pulmonary arterial hypertension with C statistics of 0.93, 0.87, and 0.85, respectively. CONCLUSIONS: Our pipeline lays the groundwork for using automated interpretation to support serial patient tracking and scalable analysis of millions of echocardiograms archived within healthcare systems.

Appropriate Reconciliation of Cardiovascular Medications After Elective Surgery and Postdischarge Acute Hospital and Ambulatory Visits.

OBJECTIVE: To describe appropriate discharge reconciliation of cardiovascular medications and assess associations with postdischarge healthcare utilization in surgical patients. DESIGN: Retrospective cohort study from January 2007 to December 2011. SETTING: An academic medical center. PATIENTS: Seven hundred and fifty-two adults undergoing elective noncardiac surgery and taking antiplatelet agents, beta-blockers, renin-angiotensin system inhibitors, or statin lipid-lowering agents before surgery. MEASUREMENTS: Primary predictor: appropriate discharge reconciliation of preoperative cardiovascular medications (continuation without documented contraindications). Primary outcomes: acute hospital visits (emergency department visits or hospitalizations) and unplanned ambulatory visits (primary care or surgical) at 30 days after surgery. RESULTS: Preoperative medications were appropriately reconciled in 436 (58.0%) patients. For individual medications, appropriate discharge reconciliation occurred for 156 of the 327 patients on antiplatelet agents (47.7%), 507 of the 624 patients on beta-blockers (81.3%), 259 of the 361 patients on renin-angiotensin system inhibitors (71.8%), and 302 of the 406 patients on statins (74.4%). In multivariable analyses, appropriate reconciliation of all preoperative medications was not associated with acute hospital (adjusted odds ratio [AOR], 0.94; 95% confidence interval [CI], 0.63-1.41) or unplanned ambulatory visits (AOR, 1.48; 95% CI, 0.94-2.35). Appropriate reconciliation of statin therapy was associated with lower odds of acute hospital visits (AOR, 0.47; 95% CI, 0.26-0.85). There were no other statistically significant associations between appropriate reconciliation of individual medications and either outcome. CONCLUSIONS: Although large gaps in appropriate discharge reconciliation of chronic cardiovascular medications were common in patients undergoing elective surgery, these gaps were not consistently associated with postdischarge acute hospital or ambulatory visits.

Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease.

OBJECTIVE: There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We assessed the cost-effectiveness of a population approach with a polypill including a statin (simvastatin 20 mg) and three antihypertensive agents (amlodipine 2.5 mg, losartan 25 mg and hydrochlorothiazide 12.5 mg) and periodic risk assessment with different risk thresholds. METHODS: We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259 146 asymptomatic UK Biobank participants aged 40-69 years. We assessed incremental costs and quality-adjusted life-years (QALYs) for polypill scenarios with the same combination of agents and doses but differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%. RESULTS: Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20%, was the optimal strategy gaining 123 QALYs (95% credible interval (CI) -173 to 387) per 10 000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice. Although less restrictive risk assessment and polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% was economically unattractive, costing £40 000 per QALY gained. Starting the polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were reduced below £240. All polypill scenarios would save costs at prices below £50. CONCLUSIONS: Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. The polypill would become cost-effective if drug prices were reduced.

Comparing the cost-effectiveness of four novel risk markers for screening asymptomatic individuals to prevent cardiovascular disease (CVD) in the US population.

BACKGROUND: High sensitivity CRP (hsCRP), coronary artery calcification on CT (CT calcium), carotid artery intima media thickness on ultrasound (cIMT) and ankle-brachial index (ABI) improve prediction of cardiovascular disease (CVD) risk, but the benefit of screening with these novel risk markers in the U.S. population is unclear. METHODS AND RESULTS: A microsimulation model evaluating lifelong cost-effectiveness for individuals aged 40-85 at intermediate risk of CVD, using 2003-2004 NHANES-III (N=3736), Framingham Heart Study, U.S. Vital Statistics, meta-analyses of independent predictive effects of the four novel risk markers and treatment effects was constructed. Using both an intention-to-treat (assumes adherence <100% and incorporates disutility from taking daily medications) and an as-treated (100% adherence and no disutility) analysis, quality adjusted life years (QALYs), lifetime costs (2014 US $), and incremental cost-effectiveness ratios (ICER in $/QALY gained) of screening with hsCRP, CT coronary calcium, cIMT and ABI were established compared with current practice, full adherence to current guidelines, and ubiquitous statin therapy. In the intention-to-treat analysis in men, screening with CT calcium was cost effective ($32,900/QALY) compared with current practice. In women, screening with hsCRP was cost effective ($32,467/QALY). In the as-treated analysis, statin therapy was both more effective and less costly than all other strategies for both men and women. CONCLUSIONS: When a substantial disutility from taking daily medication is assumed, screening men with CT coronary calcium is likely to be cost-effective whereas screening with hsCRP has value in women. The individual perceived disutility for taking daily medication should play a key role in the decision.

Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.

OBJECTIVE: To review the literature systematically to determine whether initiation of beta blockade within 45 days prior to noncardiac surgery reduces 30-day cardiovascular morbidity and mortality rates. METHODS: PubMed (up to April 2013), Embase (up to April 2013), Cochrane Central Register of Controlled Trials (up to March 2013), and conference abstracts (January 2011 to April 2013) were searched for randomized controlled trials (RCTs) and cohort studies comparing perioperative beta blockade with inactive control during noncardiac surgery. Pooled relative risks (RRs) were calculated under the random-effects model. We conducted subgroup analyses to assess how the DECREASE-I (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography), DECREASE-IV, and POISE-1 (Perioperative Ischemic Evaluation) trials influenced our conclusions. RESULTS: We identified 17 studies, of which 16 were RCTs (12 043 participants) and 1 was a cohort study (348 participants). Aside from the DECREASE trials, all other RCTs initiated beta blockade within 1 day or less prior to surgery. Among RCTs, beta blockade decreased nonfatal myocardial infarction (MI) (RR: 0.69; 95% confidence interval [CI]: 0.58 to 0.82) but increased nonfatal stroke (RR: 1.76; 95% CI: 1.07 to 2.91), hypotension (RR: 1.47; 95% CI: 1.34 to 1.60), and bradycardia (RR: 2.61; 95% CI: 2.18 to 3.12). These findings were qualitatively unchanged after the DECREASE and POISE-1 trials were excluded. Effects on mortality rate differed significantly between the DECREASE trials and other trials. Beta blockers were associated with a trend toward reduced all-cause mortality rate in the DECREASE trials (RR: 0.42; 95% CI: 0.15 to 1.22) but with increased all-cause mortality rate in other trials (RR: 1.30; 95% CI: 1.03 to 1.64). Beta blockers reduced cardiovascular mortality rate in the DECREASE trials (RR: 0.17; 95% CI: 0.05 to 0.64) but were associated with trends toward increased cardiovascular mortality rate in other trials (RR: 1.25; 95% CI: 0.92 to 1.71). These differences were qualitatively unchanged after the POISE-1 trial was excluded. CONCLUSIONS: Perioperative beta blockade started within 1 day or less before noncardiac surgery prevents nonfatal MI but increases risks of stroke, death, hypotension, and bradycardia. Without the controversial DECREASE studies, there are insufficient data on beta blockade started 2 or more days prior to surgery. Multicenter RCTs are needed to address this knowledge gap.

Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.

OBJECTIVE: To review the literature systematically to determine whether initiation of beta blockade within 45 days prior to noncardiac surgery reduces 30-day cardiovascular morbidity and mortality rates. METHODS: PubMed (up to April 2013), Embase (up to April 2013), Cochrane Central Register of Controlled Trials (up to March 2013), and conference abstracts (January 2011 to April 2013) were searched for randomized controlled trials (RCTs) and cohort studies comparing perioperative beta blockade with inactive control during noncardiac surgery. Pooled relative risks (RRs) were calculated under the random-effects model. We conducted subgroup analyses to assess how the DECREASE-I (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography), DECREASE-IV, and POISE-1 (Perioperative Ischemic Evaluation) trials influenced our conclusions. RESULTS: We identified 17 studies, of which 16 were RCTs (12,043 participants) and 1 was a cohort study (348 participants). Aside from the DECREASE trials, all other RCTs initiated beta blockade within 1 day or less prior to surgery. Among RCTs, beta blockade decreased nonfatal myocardial infarction (MI) (RR: 0.69; 95% confidence interval [CI]: 0.58 to 0.82) but increased nonfatal stroke (RR: 1.76; 95% CI:1.07 to 2.91), hypotension (RR: 1.47; 95% CI: 1.34 to 1.60), and bradycardia (RR: 2.61; 95% CI: 2.18 to 3.12). These findings were qualitatively unchanged after the DECREASE and POISE-1 trials were excluded. Effects on mortality rate differed significantly between the DECREASE trials and other trials. Beta blockers were associated with a trend toward reduced all-cause mortality rate in the DECREASE trials (RR: 0.42; 95% CI: 0.15 to 1.22) but with increased all-cause mortality rate in other trials (RR: 1.30; 95% CI: 1.03 to 1.64). Beta blockers reduced cardiovascular mortality rate in the DECREASE trials (RR:0.17; 95% CI: 0.05 to 0.64) but were associated with trends toward increased cardiovascular mortality rate in other trials (RR: 1.25; 95% CI: 0.92 to 1.71). These differences were qualitatively unchanged after the POISE-1 trial was excluded. CONCLUSIONS: Perioperative beta blockade started within 1 day or less before noncardiac surgery prevents nonfatal MI but increases risks of stroke, death, hypotension, and bradycardia. Without the controversial DECREASE studies, there are insufficient data on beta blockade started 2 or more days prior to surgery. Multicenter RCTs are needed to address this knowledge gap.

Prehospital electrocardiographic manifestations of acute myocardial ischemia independently predict adverse hospital outcomes.

BACKGROUND: Prehospital electrocardiography (PH ECG) is becoming the standard of care for patients activating Emergency Medical Services for symptoms of acute coronary syndrome (ACS). Little is known about the prognostic value of ischemia found on PH ECG. OBJECTIVE: The purpose of this study was to determine whether manifestations of acute myocardial ischemia on PH ECG are predictive of adverse hospital outcomes. METHODS: This study was a retrospective analysis of all PH ECGs recorded in 630 patients who called 911 for symptoms of ACS and were enrolled in a prospective clinical trial. ST-segment monitoring software was added to the PH ECG device with automatic storage and transmission of ECGs to the destination Emergency Department. Patient medical records were reviewed for adverse hospital outcomes. RESULTS: In 630 patients who called 911 for ACS symptoms, 270 (42.9%) had PH ECG evidence of ischemia. Overall, 37% of patients with PH ECG ischemia had adverse hospital outcomes compared with 27% of patients without PH ECG ischemia (p < 0.05). Those with PH ECG ischemia were 1.55 times more likely to have adverse hospital outcomes than those without PH ECG ischemia (95% CI 1.09-2.21; p < 0.05), after controlling for other predictors of adverse hospital outcomes (i.e., age, sex, and medical history). CONCLUSIONS: Evidence of ischemia on PH ECG is an independent predictor of adverse hospital outcomes. ST-segment monitoring in the prehospital setting can identify high-risk patients with symptoms of ACS and provide important prognostic information at presentation to the Emergency Department.

Personalized prediction of lifetime benefits with statin therapy for asymptomatic individuals: a modeling study.

BACKGROUND: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. METHODS AND FINDINGS: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. CONCLUSIONS: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy.

Secondhand smoke exposure and quality of life in patients with heart failure.

BACKGROUND: Secondhand smoke (SHS) exposure is associated with an increased risk of atherosclerotic heart disease and cardiac events. We sought to assess the effect of SHS on health-related quality of life (HRQOL) in patients with heart failure. METHODS: Current nonsmokers with heart failure (N = 205) were enrolled in a cohort study. Exposure to SHS was assessed with a validated exposure questionnaire and a high-sensitivity assay for urinary cotinine level. Multidimensional HRQOL was evaluated with the RAND 36-Item Short Form Health Survey, which assesses 8 domains on a scale of 0 (worst) to 100 (best): physical functioning, bodily pain, role limitations due to physical health problems (role physical), role limitations due to emotional/personal problems (role emotional), emotional well-being, social functioning, energy/fatigue, and general health perceptions. A subset of patients (n = 75) agreed to assessment of functional status with a 6-minute walk test. RESULTS: Self-reported exposure to SHS was associated with generally lower HRQOL scores in univariate analysis, with statistically and clinically significant reductions in 3 subscale scores: role physical (22.2 points), emotional well-being (11.0 points), and role emotional (16.2 points). Even after adjustment for clinical factors, such as age, sex, New York Heart Association class of heart failure, comorbidities, and medications, exposure to SHS remained an independent predictor of HRQOL scores in these domains. When increasing quartiles of urinary cotinine level were used as the exposure measure, qualitatively similar results were obtained. CONCLUSIONS: Even low levels of SHS are associated with lower scores in several aspects of HRQOL. Physicians should advise patients with heart failure and their families to avoid SHS exposure.

Comparative effectiveness and cost-effectiveness of computed tomography screening for coronary artery calcium in asymptomatic individuals.

OBJECTIVES: The aim of this study was to assess the (cost-) effectiveness of screening asymptomatic individuals at intermediate risk of coronary heart disease (CHD) for coronary artery calcium with computed tomography (CT). BACKGROUND: Coronary artery calcium on CT improves prediction of CHD. METHODS: A Markov model was developed on the basis of the Rotterdam Study. Four strategies were evaluated: 1) current practice; 2) current prevention guidelines for cardiovascular disease; 3) CT screening for coronary calcium; and 4) statin therapy for all individuals. Asymptomatic individuals at intermediate risk of CHD were simulated over their remaining lifetime. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios were calculated. RESULTS: In men, CT screening was more effective and more costly than the other 3 strategies (CT vs. current practice: +0.13 QALY [95% confidence interval (CI): 0.01 to 0.26], +$4,676 [95% CI: $3,126 to $6,339]; CT vs. statin therapy: +0.04 QALY [95% CI: -0.02 to 0.13], +$1,951 [95% CI: $1,170 to $2,754]; and CT vs. current guidelines: +0.02 QALY [95% CI: -0.04 to 0.09], +$44 [95% CI: -$441 to $486]). The incremental cost-effectiveness ratio of CT calcium screening was $48,800/QALY gained. In women, CT screening was more effective and more costly than current practice (+0.13 QALY [95% CI: 0.02 to 0.28], +$4,663 [95% CI: $3,120 to $6,277]) and statin therapy (+0.03 QALY [95% CI: -0.03 to 0.12], +$2,273 [95% CI: $1,475 to $3,109]). However, implementing current guidelines was more effective compared with CT screening (+0.02 QALY [95% CI: -0.03 to 0.07]), only a little more expensive (+$297 [95% CI: -$8 to $633]), and had a lower cost per additional QALY ($33,072/QALY vs. $35,869/QALY). Sensitivity analysis demonstrated robustness of results in women but considerable uncertainty in men. CONCLUSIONS: Screening for coronary artery calcium with CT in individuals at intermediate risk of CHD is probably cost-effective in men but is unlikely to be cost-effective in women.

Remote second-hand tobacco exposure in flight attendants is associated with systemic but not pulmonary hypertension.

BACKGROUND: Second-hand tobacco smoke has been associated with cardiopulmonary dysfunction. We sought to examine the residual effects of remote second-hand smoke exposure on resting and exercise cardiopulmonary hemodynamics. We hypothesized that remote secondhand smoke exposure results in persistent cardiopulmonary hemodynamic abnormalities. METHODS: Participants were non-smoking flight attendants who worked in airline cabins prior to the in-flight tobacco ban. Participants underwent clinical evaluations and completed smoke exposure questionnaires. We used Doppler echocardiography to measure pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) at rest and during supine bicycle ergometer exercise, using the validated formula TRV/VTIRVOT x 10 + 0.16, where VTIRVOT is the velocity time integral at the right ventricular outflow tract and TRV is the tricuspid regurgitation velocity. The group was divided into quartiles according to the degree of smoke exposure. Analysis of variance was used to determine the differences in hemodynamic outcomes. RESULTS: Seventy-nine flight attendants were included in our analysis. Baseline characteristics among participants in each quartile of smoke exposure were similar except for history of systemic hypertension, which was more prevalent in the highest quartile. Peak exercise PASP rose to the same degree in all test groups (mean PASP 44 mm Hg, p = 0.25), and PVR increased by approximately 27% in all quartiles. There was no significant difference in pulmonary artery systolic pressure or pulmonary vascular resistance among quartiles of smoke exposure. CONCLUSIONS: We found that remote heavy second-hand smoke exposure from in-flight tobacco is associated with systemic hypertension but does not have demonstrable pulmonary hemodynamic consequences.