Arterial thromboembolic events preceding the diagnosis of cancer in older persons.

Cancer patients face an increased risk of arterial thromboembolism; however, it is uncertain when this excess risk begins. This study evaluated the risk of arterial thromboembolism before cancer diagnosis. Using the population-based Surveillance Epidemiology and End Results-Medicare linked dataset, we identified 374 331 patients ≥67 years of age with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, uterine, pancreatic, gastric cancer, or non-Hodgkin lymphoma from 2005 through 2013. Cancer patients were individually matched by demographics and comorbidities to Medicare beneficiaries without cancer, who served as controls. Validated diagnosis codes were used to identify arterial thromboembolic events, defined as a composite of myocardial infarction or ischemic stroke. The Mantel-Haenszel estimator was used to compare risks of arterial thromboembolic events between cancer and noncancer groups during 30-day periods in the 360 days before date of cancer diagnosis. From 360 to 151 days before cancer diagnosis, the 30-day interval risks of arterial thromboembolic events were similar between cancer patients and matched controls. From 150 to 1 day before cancer diagnosis, the interval 30-day risks of arterial thromboembolic events were higher in cancer patients vs matched controls, progressively increasing as the cancer diagnosis date approached and peaking during the 30 days immediately before cancer diagnosis, when 2313 (0.62%) cancer patients were diagnosed with an arterial thromboembolic event vs 413 (0.11%) controls (odds ratio, 5.63; 95% confidence interval, 5.07-6.25). In conclusion, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis in older persons and peaks in the 30 days before.

New diagnosis of cancer and the risk of subsequent cerebrovascular events.

OBJECTIVE: We aimed to evaluate the association between cancer and cerebrovascular disease in a prospective cohort study with adjudicated cerebrovascular diagnoses. METHODS: We analyzed participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were 45 years and older and had Medicare coverage for 365 days before their baseline study visit. Participants with a history of cancer or cerebrovascular events were excluded. The time-dependent exposure was a new diagnosis of malignant cancer identified through Medicare claims algorithms. Participants were prospectively followed from their baseline study visit (2003-2007) through 2014 for the outcome of a neurologist-adjudicated cerebrovascular event defined as a composite of stroke (ischemic or hemorrhagic) or TIA. Cox regression was used to evaluate the association between a new cancer diagnosis and subsequent cerebrovascular events. Follow-up time was modeled in discrete time periods to fulfill the proportional hazard assumption. RESULTS: Among 6,602 REGARDS participants who met eligibility criteria, 1,149 were diagnosed with cancer during follow-up. Compared to no cancer, a new cancer diagnosis was associated with subsequent cerebrovascular events in the first 30 days after diagnosis (hazard ratio 6.1, 95% confidence interval 2.7-13.7). This association persisted after adjustment for demographics, region of residence, and vascular risk factors (hazard ratio 6.6, 95% confidence interval 2.7-16.0). There was no association between cancer diagnosis and incident cerebrovascular events beyond 30 days. Cancers considered high risk for venous thromboembolism demonstrated the strongest associations with cerebrovascular event risk. CONCLUSION: A new diagnosis of cancer is associated with a substantially increased short-term risk of cerebrovascular events.

Cohort Study of ECG Left Ventricular Hypertrophy Trajectories: Ethnic Disparities, Associations With Cardiovascular Outcomes, and Clinical Utility.

BACKGROUND: ECG left ventricular hypertrophy (LVH) is a well-known predictor of cardiovascular disease. However, no prior study has characterized patterns of presence/absence of ECG LVH ("ECG LVH trajectories") across the adult lifespan in both sexes and across ethnicities. We examined: (1) correlates of ECG LVH trajectories; (2) the association of ECG LVH trajectories with incident coronary heart disease, transient ischemic attack, ischemic stroke, hemorrhagic stroke, and heart failure; and (3) reclassification of cardiovascular disease risk using ECG LVH trajectories. METHODS AND RESULTS: We performed a cohort study among 75 412 men and 107 954 women in the Northern California Kaiser Permanente Medical Care Program who had available longitudinal exposures of ECG LVH and covariates, followed for a median of 4.8 (range <1-9.3) years. ECG LVH was measured by Cornell voltage-duration product. Adverse trajectories of ECG LVH (persistent, new development, or variable pattern) were more common among blacks and Native American men and were independently related to incident cardiovascular disease with hazard ratios ranging from 1.2 for ECG LVH variable pattern and transient ischemic attack in women to 2.8 for persistent ECG LVH and heart failure in men. ECG LVH trajectories reclassified 4% and 7% of men and women with intermediate coronary heart disease risk, respectively. CONCLUSIONS: ECG LVH trajectories were significant indicators of coronary heart disease, stroke, and heart failure risk, independently of level and change in cardiovascular disease risk factors, and may have clinical utility.

P wave area for quantitative electrocardiographic assessment of left atrial remodeling.

BACKGROUND: Left atrial (LA) dilation provides a substrate for mitral regurgitation (MR) and atrial arrhythmias. ECG can screen for LA dilation but standard approaches do not assess LA geometry as a continuum, as does non-invasive imaging. This study tested ECG-quantified P wave area as an index of LA geometry. METHODS AND RESULTS: 342 patients with CAD underwent ECG and CMR within 7 (0.1±1.4) days. LA area on CMR correlated best with P wave area in ECG lead V1 (r = 0.42, p<0.001), with lesser correlations for P wave amplitude and duration. P wave area increased stepwise in relation to CMR-evidenced MR severity (p<0.001), with similar results for MR on echocardiography (performed in 86% of patients). Pulmonary arterial (PA) pressure on echo was increased by 50% among patients in the highest (45±14 mmHg) vs. the lowest (31±9 mmHg) P wave area quartile of the population. In multivariate regression, CMR and echo-specific models demonstrated P wave area to be independently associated with LA size after controlling for MR, as well as echo-evidenced PA pressure. Clinical follow-up (mean 2.4±1.9 years) demonstrated ECG and CMR to yield similar results for stratification of arrhythmic risk, with a 2.6-fold increase in risk for atrial fibrillation/flutter among patients in the top P wave area quartile of the population (CI 1.1-5.9, p = 0.02), and a 3.2-fold increase among patients in the top LA area quartile (CI 1.4-7.0, p = 0.005). CONCLUSIONS: ECG-quantified P wave area provides an index of LA remodeling that parallels CMR-evidenced LA chamber geometry, and provides similar predictive value for stratification of atrial arrhythmic risk.

Q wave area for stratification of global left ventricular infarct size: comparison to conventional ECG assessment using Selvester QRS-score.

OBJECTIVES: Left ventricular (LV) infarct size is a prognostic determinant after acute myocardial infarction (AMI). ECG data have been used to measure infarct size, but conventional approaches use multiparametric algorithms that have limited clinical applicability. This study tested a novel ECG approach - based solely on Q wave area - for calculation of LV infarct size. METHODS: Serial 12-lead ECGs were performed in AMI patients. Computerized software was used to quantify Q wave area (summed across surface ECG leads) and Selvester QRS-score components. ECG analysis was compared to the reference of myocardial infarct size quantified by delayed enhancement cardiac magnetic resonance. RESULTS: Overall, 158 patients underwent ECG during early (4±0.4) and follow-up (29±5 days) post-AMI time points. Selvester QRS-score and Q wave area increased stepwise with LV infarct size (P<0.001). Whereas both methods manifested marked increases at a threshold of 10% LV infarction, magnitude was greater for Q wave area (>2.5-fold) than Selvester QRS-score (

T-wave alternans and ST depression assessment identifies low risk individuals with ischemic cardiomyopathy in the absence of left ventricular hypertrophy.

BACKGROUND: Although ECG left ventricular hypertrophy (LVH) by Cornell product (CP) predicts increased mortality in patients with ischemic cardiomyopathy (ICM), those without CP LVH remain at relatively high risk. We examined whether T-wave alternans (TWA) testing and ST depression can improve risk stratification in these patients. METHODS AND RESULTS: This study examined 317 patients with ICM, nonsustained ventricular tachycardia, and a resting ECG in sinus rhythm, who presented for electrophysiology and TWA testing, and potential implantable cardioverter defibrillator (ICD) implantation. LVH was defined by CP :[(RaVL + SV3 ) +6 mm in women] × QRS duration > 2440 mm * msec. ST depression was examined as a categorical variable using an established threshold of depression of ≥50 µV in V5 or V6 . In Cox multivariate models, abnormal TWA testing and ST depression were independent predictors of mortality in patients without CP LVH (HR 2.52, CI 1.09-5.80, P = 0.030 and HR 2.87, CI 1.41-5.81, P = 0.004, respectively). Individuals with no LVH by CP, normal TWA, and no significant ST depression, comprised 23% of the study population and had a 5.6% 3-year mortality, compared to an overall 20% mortality. CONCLUSIONS: TWA and ST depression testing are strong predictors of mortality among ICM patients without CP LVH, with normal testing conversely predicting low 3-year mortality. Thus, risk assessment with TWA testing and a resting ECG can identify ICM patients at low risk who may be less likely to benefit from ICD implantation.

Serial assessment of the electrocardiographic strain pattern for prediction of new-onset heart failure during antihypertensive treatment: the LIFE study.

AIMS: Although the presence of the electrocardiographic (ECG) strain pattern has been associated with an increased risk of developing heart failure (HF), the relationship of regression vs. persistence vs. development of new ECG strain to subsequent HF is unclear. METHODS AND RESULTS: Electrocardiographic strain was evaluated at baseline and at year-1 in 7265 hypertensive patients without HF treated with atenolol- or losartan-based regimens. During 3.9 ± 0.7 years of follow-up after the year-1 ECG, 154 patients (2.1%) were hospitalized for HF. Five-year HF incidence was lowest in patients with no ECG strain (1.6%), intermediate in patients with regression of strain (5.4%), and highest in patients with persistent (7.1%) or new strain (7.0%; P< 0.0001 across groups). In the Cox multivariable analyses adjusting for the known predictive value of in-treatment ECG left ventricular hypertrophy by the Cornell product and Sokolow-Lyon voltage, in-treatment QRS duration, systolic and diastolic pressure, incident myocardial infarction and atrial fibrillation, randomized treatment and other risk factors for HF, regression of strain [hazards ratio (HR) 2.4, 95% confidence interval (CI) 1.2-5.0], persistence of strain (HR 1.9, 95% CI 1.2-3.2), and development of new ECG strain (HR 2.3, 95% CI 1.2-4.4) were all independently associated with an increased risk of new HF compared with the absence of ECG strain on both baseline and year-1 ECGs. CONCLUSION: The development of new ECG strain or persistence of ECG strain between baseline and year-1 is associated with an increased risk of HF. The regression of ECG strain between baseline and year-1 does not convey a decreased risk of HF. CLINICAL TRIALS REGISTRATION: http://clinicaltrials.gov/ct/show/NCT00338260.

Prognostic value of changes in the electrocardiographic strain pattern during antihypertensive treatment: the Losartan Intervention for End-Point Reduction in Hypertension Study (LIFE).

BACKGROUND: The presence of the ECG strain pattern of lateral ST depression and T-wave inversion at baseline has been associated with an increased risk of cardiovascular morbidity and mortality; however, the independent predictive value for cardiovascular outcomes of regression versus persistence versus development of new ECG strain during antihypertensive therapy is unclear. METHODS AND RESULTS: ECG strain was evaluated at baseline and after 1 year of therapy in 7409 hypertensive patients in the LIFE study (Losartan Intervention For End-point reduction in hypertension) treated in a blinded manner with atenolol- or losartan-based regimens. During 3.8+/-0.8 years of follow-up after the year 1 ECG, cardiovascular death occurred in 236 patients (3.2%), myocardial infarction in 198 (2.7%), stroke in 313 (4.2%), the LIFE composite end point of these 3 events in 600 (8.1%), sudden death in 92 (1.2%), and death due to any cause in 486 (6.6%). Strain was absent on both baseline and year 1 ECGs in 6323 patients (85.3%), regressed from baseline to year 1 in 245 (3.3%), persisted on both ECGs in 549 (7.4%), and was absent at baseline but developed by year 1 in 292 patients (3.9%). Compared with absence of strain on both ECGs, development of new ECG strain was associated with 2.8- to 4.7-fold higher event rates; patients with regression or persistence of strain had intermediate event rates. In Cox multivariable analyses with adjustment for the known predictive value of in-treatment ECG left ventricular hypertrophy by Cornell product and Sokolow-Lyon voltage, in-treatment systolic and diastolic pressure, randomized treatment, and standard cardiovascular risk factors, development of new ECG strain was independently associated with increased risks of cardiovascular death (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.56 to 3.76), myocardial infarction (HR 1.95, 95% CI 1.11 to 3.44), stroke (HR 1.98, 95% CI 1.30 to 3.01), the LIFE composite end point (HR 2.05, 95% CI 1.51 to 2.78), sudden cardiac death (HR 2.19, 95% CI 1.06 to 4.53), and all-cause mortality (HR 1.92, 95% CI 1.37 to 2.69), whereas the risk associated with regression or persistence of strain was attenuated. CONCLUSIONS: Development of new ECG strain is associated with an increased risk of cardiovascular morbidity and mortality and of all-cause mortality in the setting of antihypertensive therapy and regression of ECG left ventricular hypertrophy.

Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality.

OBJECTIVES: The purpose of this study was to examine the association of all-cause death with the coronary computed tomographic angiography (CCTA)-defined extent and severity of coronary artery disease (CAD). BACKGROUND: The prognostic value of identifying CAD by CCTA remains undefined. METHODS: We examined a single-center consecutive cohort of 1,127 patients > or =45 years old with chest symptoms. Stenosis by CCTA was scored as minimal (<30%), mild (30% to 49%), moderate (50% to 69%), or severe (> or =70%) for each coronary artery. Plaque was assessed in 3 ways: 1) moderate or obstructive plaque; 2) CCTA score modified from Duke coronary artery score; and 3) simple clinical scores grading plaque extent and distribution. A 15.3 +/- 3.9-month follow-up of all-cause death was assessed using Cox proportional hazards models adjusted for pretest CAD likelihood and risk factors. Deaths were verified by the Social Security Death Index. RESULTS: The CCTA predictors of death included proximal left anterior descending artery stenosis and number of vessels with > or =50% and > or =70% stenosis (all p < 0.0001). A modified Duke CAD index, an angiographic score integrating proximal CAD, plaque extent, and left main (LM) disease, improved risk stratification (p < 0.0001). Patients with <50% stenosis had the highest survival at 99.7%. Survival worsened with higher-risk Duke scores, ranging from 96% survival for 1 stenosis > or =70% or 2 stenoses > or =50% (p = 0.013) to 85% survival for > or =50% LM artery stenosis (p < 0.0001). Clinical scores measuring plaque burden and distribution predicted 5% to 6% higher absolute death rate (6.6% vs. 1.6% and 8.4% vs. 2.5%; p = 0.05 for both). CONCLUSIONS: In patients with chest pain, CCTA identifies increased risk for all-cause death. Importantly, a negative CCTA portends an extremely low risk for death.

Diagnostic impact of SPECT image display on assessment of obstructive coronary artery disease.

BACKGROUND: Diagnostic assessment of myocardial perfusion impacts the management of patients with suspected coronary artery disease (CAD). Although various image displays are available for single photon emission computed tomography (SPECT) interpretation, the effects of display differences on SPECT interpretation remain undetermined. METHODS AND RESULTS: We studied 183 patients undergoing SPECT, including 131 consecutive patients referred for angiography and 52 at low CAD risk. Studies were visually interpreted by use of color and gray images, with readers blinded to the results of the other display. In accordance with established criteria, a summed stress score (SSS) of 4 or greater was considered abnormal. The prevalence of abnormal SPECT findings was higher with gray images than with color images (54% vs 48%, P < .001) based on a uniform criterion (SSS > or =4). However, color images yielded equivalent sensitivity (79% vs 82%, P = .7) and improved specificity for global (50% vs 33%, P = .02) and vessel-specific CAD involving the right coronary artery (P < .01) and left anterior descending artery (P < .05). When the criterion for gray images was adjusted upward (SSS > or =5) to reflect increased mean defect severity (SSS of 5.1 vs 4.4, P = .01), gray and color images provided equivalent sensitivity and specificity for global and vessel-specific CAD. CONCLUSIONS: SPECT interpretation can vary according to image display as a result of differences in perfusion defect severity. Adjustment of abnormality criteria for gray images to reflect minor increases in defect severity provides equivalent diagnostic performance of gray and color displays for CAD assessment.

Usefulness of quantitative assessment of electrocardiographic ST depression for predicting new-onset heart failure in American Indians (from the Strong Heart Study).

The qualitative electrocardiographic strain pattern of ST depression (STD) and T-wave inversion is strongly associated with coronary heart disease and left ventricular hypertrophy and is an independent predictor of new-onset heart failure in hypertensive participants. However, whether quantitative measures of STD in the lateral precordial leads predict new heart failure is unclear. Digital electrocardiograms were examined in 2,059 American-Indian participants in the second Strong Heart Study examination with no history of heart failure. The absolute magnitude of ST segment deviation was measured using computer to the nearest 5 microV in leads V(5) and V(6). During 5.7 +/-1.4 years of follow-up, heart failure developed in 77 participants (3.7%). Participants who developed heart failure had greater STD in leads V(5) or V(6) (-11 +/- 35 vs 12 +/- 27 microV; p <0.001) than those who did not. In univariate Cox analyses, STD was a significant predictor of new heart failure, with each 10-microV greater STD associated with a 31% greater risk of heart failure (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.24 to 1.39). Increasing STD grouped according to quartiles was strongly associated with the development of heart failure, with stepwise increasing risk of heart failure compared with the lowest quartile of STD for the second (HR 2.39, 95% CI 0.77 to 7.40), third (HR 3.01, 95% CI 1.00 to 9.08), and fourth quartiles of STD (HR 9.06, 95% CI 3.26 to 25.16). In Cox multivariate analyses controlling for age, gender, diabetes, coronary heart disease, albuminuria, and other baseline risk factors, STD remained a significant predictor of incident heart failure (HR 1.22, 95% CI 1.13 to 1.32 per 10-muV increment in STD; p <0.001). In conclusion, increasing STD in lateral precordial leads is strongly associated with increased risk of developing heart failure independent of other risk factors for new heart failure.

Quantitative assessment of electrocardiographic strain predicts increased left ventricular mass: the Strong Heart Study.

OBJECTIVES: This study was designed to examine the relation of computer-measured ST depression (STdep) in the lateral precordial leads to the presence of left ventricular hypertrophy (LVH). BACKGROUND: Qualitative abnormalities of repolarization in the lateral precordial leads of the electrocardiogram, as manifested by the strain pattern of T-wave inversion and STdep, are markers for LVH and adverse prognosis. However, the independent relationship of increased left ventricular (LV) mass to quantitative measures of STdep in these leads remains unclear. METHODS: Electrocardiograms and echocardiograms were examined in the second Strong Heart Study examination in 1,595 American Indian participants without evident coronary disease. The absolute magnitude of ST segment deviation above or below isoelectric baseline was measured by computer in leads V(5) and V(6), and participants were grouped according to gender-specific quartiles of maximal STdep. Left ventricular hypertrophy was defined by indexed LV mass >49.2 g/m(2.7) in men and >46.7 g/m(2.7) in women. RESULTS: Increasing STdep was associated with older age, greater pulse pressure, serum fibrinogen levels and urinary albumin/creatinine ratios, and with stepwise increases in LV mass (145 +/- 28 vs. 150 +/- 33 vs. 156 +/- 36 vs. 164 +/- 43 g, p < 0.001), indexed LV mass (38.2 +/- 7.7 vs. 39.3 +/- 8.7 vs. 40.5 +/- 9.4 vs. 44.0 +/- 11.0 g/m(2.7), p < 0.001), and prevalence of LVH (11.6 vs. 19.1 vs. 21.5 vs. 31.2%, p < 0.001). After controlling for clinical differences, increasing STdep remained strongly associated with increased prevalence of LVH (p = 0.0001). CONCLUSIONS: In the absence of evidence of coronary disease, increasing STdep in the lateral precordial leads is associated with increasing LV mass and increased prevalence of anatomic LVH.