Rory B. Weiner

ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate Use Criteria for Echocardiography

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Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction.

OBJECTIVES The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is superior to standard of care (SOC) management. BACKGROUND It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone. METHODS In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography. RESULTS Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP-guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP-guided care as younger subjects. Compared with SOC, NT-proBNP-guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes. CONCLUSIONS In patients with HF due to LV systolic dysfunction, NT-proBNP-guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390).

ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate use criteria for echocardiography

The American College of Cardiology Foundation (ACCF), in partnership with the American Society of Echocardiography (ASE) and along with key specialty and subspecialty societies, conducted a review of common clinical scenarios where echocardiography is frequently considered. This document combines and updates the original transthoracic and transesophageal echocardiography appropriateness criteria published in 2007 (1) and the original stress echocardiography appropriateness criteria published in 2008 (2). This revision reflects new clinical data, reflects changes in test utilization patterns,and clarifies echocardiography use where omissions or lack of clarity existed in the original criteria.The indications (clinical scenarios)were derived from common applications or anticipated uses, as well as from current clinical practice guidelines and results of studies examining the implementation of the original appropriate use criteria (AUC).The 202 indications in this document were developed by a diverse writing group and scored by a separate independent technical panel on a scale of 1 to 9,to designate appropriate use(median 7 to 9), uncertain use(median 4 to 6), and inappropriate use (median 1 to 3). Ninety-seven indications were rated as appropriate, 34 were rated as uncertain, and 71 were rated as inappropriate. In general,the use of echocardiography for initial diagnosis when there is a change in clinical status or when the results of the echocardiogram are anticipated to change patient management were rated appropriate. Routine testing when there was no change in clinical status or when results of testing were unlikely to modify management were more likely to be inappropriate than appropriate/uncertain.The AUC for echocardiography have the potential to impact physician decision making,healthcare delivery, and reimbursement policy. Furthermore,recognition of uncertain clinical scenarios facilitates identification of areas that would benefit from future research.

Cardiovascular screening in college athletes with and without electrocardiography: a cross-sectional study.

BACKGROUND Although cardiovascular screening is recommended for athletes before participating in sports, the role of 12-lead electrocardiography (ECG) remains uncertain. To date, no prospective data that compare screening with and without ECG have been available. OBJECTIVE To compare the performance of preparticipation screening limited to medical history and physical examination with a strategy that integrates these with ECG. DESIGN Cross-sectional comparison of screening strategies. SETTING University Health Services, Harvard University, Cambridge, Massachusetts. PARTICIPANTS 510 collegiate athletes who received cardiovascular screening before athletic participation. MEASUREMENTS Each participant had routine history and examination-limited screening and ECG. They received transthoracic echocardiography (TTE) to detect or exclude cardiac findings with relevance to sports participation. The performance of screening with history and examination only was compared with that of screening that integrated history, examination, and ECG. RESULTS Cardiac abnormalities with relevance to sports participation risk were observed on TTE in 11 of 510 participants (prevalence, 2.2%). Screening with history and examination alone detected abnormalities in 5 of these 11 athletes (sensitivity, 45.5% [95% CI, 16.8% to 76.2%]; specificity, 94.4% [CI, 92.0% to 96.2%]). Electrocardiography detected 5 additional participants with cardiac abnormalities (for a total of 10 of 11 participants), thereby improving the overall sensitivity of screening to 90.9% (CI, 58.7% to 99.8%). However, including ECG reduced the specificity of screening to 82.7% (CI, 79.1% to 86.0%) and was associated with a false-positive rate of 16.9% (vs. 5.5% for screening with history and examination only). LIMITATION Definitive conclusions regarding the effect of ECG inclusion on sudden death rates cannot be made. CONCLUSION Adding ECG to medical history and physical examination improves the overall sensitivity of preparticipation cardiovascular screening in athletes. However, this strategy is associated with an increased rate of false-positive results when current ECG interpretation criteria are used. PRIMARY FUNDING SOURCE None.

Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training

Non‐technical summary  MicroRNA (miRNA) molecules are essential intracellular mediators of numerous biological processes including angiogenesis, inflammation, and mitochondrial metabolism. Recently, it has been shown that miRNAs are secreted into the bloodstream and that circulating miRNAs (c‐miRNAs) may serve important endocrine functions. This study examined plasma profiles of specific c‐miRNAs in healthy competitive athletes at rest and during exhaustive exercise testing, before and after a 90 day period of exercise training. In this setting, we observed four distinct patterns of c‐miRNA response to exercise: (1) c‐miRNAs up‐regulated by acute exhaustive exercise before and after sustained exercise training, (2) c‐miRNAs responsive to acute exhaustive exercise before but not after sustained exercise training, (3) c‐miRNAs responsive only to sustained exercise training, and (4) non‐responsive c‐miRNAs. These findings set the stage for further work aimed at defining the role of c‐miRNAs as fitness biomarkers and physiological mediators of exercise‐induced cardiovascular adaptation.

Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction The Role of Abnormal Peripheral Oxygen Extraction

Background—Exercise capacity as measured by peak oxygen uptake (VO2) is similarly impaired in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). However, characterization of how each component of VO2 changes in response to incremental exercise in HFpEF versus HFrEF has not been previously defined. We hypothesized that abnormally low peripheral o2 extraction (arterio-mixed venous o2 content difference, [C(a-v)o2]) during exercise significantly contributes to impaired exercise capacity in HFpEF. Methods and Results—We performed maximum incremental cardiopulmonary exercise testing with invasive hemodynamic monitoring on 104 patients with symptomatic NYHA II to IV heart failure (HFpEF, n=48, peak VO2=13.9±0.5 mL kg−1 min−1, mean±SEM, and HFrEF, n=56, peak VO2=12.1±0.5 mL kg−1 min−1) and 24 control subjects (peak VO2 27.0±1.7 mL kg−1 min−1). Peak exercise C(a-v)o2 was lower in HFpEF compared with HFrEF (11.5±0.27 versus 13.5±0.34 mL/dL, respectively, P<0.0001), despite no differences in age, hemoglobin level, peak respiratory exchange ratio, CaO2, or cardiac filling pressures. Peak C(a-v)o2 and peak heart rate emerged as the leading predictors of peak VO2 in HFpEF. Impaired peripheral o2 extraction was the predominant limiting factor to exercise capacity in 40% of patients with HFpEF and was closely related to elevated systemic blood pressure during exercise (r=0.49, P=0.0005). Conclusions—In the first study to directly measure C(a-v)o2 throughout exercise in HFpEF, HFrEF, and normals, we found that peak C(a-v)o2 was a major determinant of exercise capacity in HFpEF. The important functional limitation imposed by impaired o2 extraction may reflect intrinsic abnormalities in skeletal muscle or peripheral microvascular function, and represents a potential target for therapeutic intervention.

Long Term Anabolic-Androgenic Steroid Use is Associated with Left Ventricular Dysfunction

Background—Although illicit anabolic-androgenic steroid (AAS) use is widespread, the cardiac effects of long-term AAS use remain inadequately characterized. We compared cardiac parameters in weightlifters reporting long-term AAS use to those in otherwise similar weightlifters without prior AAS exposure. Methods and Results—We performed 2D tissue-Doppler and speckle-tracking echocardiography to assess left ventricular (LV) ejection fraction, LV systolic strain, and conventional indices of diastolic function in long-term AAS users (n=12) and otherwise similar AAS nonusers (n=7). AAS users (median [quartile 1, quartile 3] cumulative lifetime AAS exposure, 468 [169, 520] weeks) closely resembled nonusers in age, prior duration of weightlifting, and current intensity of weight training. LV structural parameters were similar between the two groups; however, AAS users had significantly lower LV ejection fraction (50.6% [48.4, 53.6] versus 59.1% [58.0%, 61.7%]; P=0.003 by two-tailed Wilcoxon rank sum test), longitudinal strain (16.9% [14.0%, 19.0%] versus 21.0% [20.2%, 22.9%]; P=0.004), and radial strain (38.3% [28.5%, 43.7%] versus 50.1% [44.3%, 61.8%]; P=0.02). Ten of the 12 AAS users showed LV ejection fractions below the accepted limit of normal (≥55%). AAS users also demonstrated decreased diastolic function compared to nonusers as evidenced by a markedly lower early peak tissue velocity (7.4 [6.8, 7.9] cm/s versus 9.9 [8.3, 10.5] cm/s; P=0.005) and early-to-late diastolic filling ratio (0.93 [0.88, 1.39] versus 1.80 [1.48, 2.00]; P=0.003). Conclusions—Cardiac dysfunction in long-term AAS users appears to be more severe than previously reported and may be sufficient to increase the risk of heart failure.

Performance of the 2010 European Society of Cardiology criteria for ECG interpretation in athletes

Background The European Society of Cardiology (ESC) recently published revised criteria for ECG interpretation in the athlete. Objective To examine the performance of the 2010 ESC ECG criteria in a population of athletes undergoing preparticipation cardiovascular disease screening. Methods University athletes (n=508) underwent routine medical history/physical examination and ECG before athletic participation. Transthoracic echocardiography (TTE) was also performed on each participant to detect or exclude cardiac findings with relevance to sport participation. Screening test statistics were calculated to determine the performance of the 2010 ESC criteria, and the performance of the 2010 criteria was compared with the 2005 criteria. Results Application of the 2010 ESC criteria, compared with the 2005 criteria, reduced the number of participants with abnormal ECG findings from 83/508 (16.3%) to 49/508 (9.6%). The reduction in the number of abnormal ECGs was driven by the reclassification of participants with isolated QRS voltage criteria for left ventricular hypertrophy from abnormal to normal. Of the 49 participants with abnormal ECGs, 14/49 (29%) had a single ECG abnormality and 35/49 (71%) had two or more abnormalities. The use of the 2010 criteria was associated with improved specificity (reduction in the false positive rate) and preserved sensitivity when compared with the 2005 criteria. Conclusion Application of the 2010 ESC criteria for ECG interpretation in the athlete improves the accuracy of an ECG-inclusive preparticipation screening strategy by reducing the rate of false positive ECGs.

Early Repolarization Pattern in Competitive Athletes Clinical Correlates and the Effects of Exercise Training

Background— Inferior lead early repolarization pattern (ERP) recently has been associated with sudden cardiac death. Although ERP is common among athletes, prevalence, ECG lead distribution, clinical characteristics, and effects of physical training remain uncertain. We sought to examine the nonanterior ERP in competitive athletes. Methods and Results— ERP was assessed in a cross-sectional cohort of collegiate athletes (n=879). The relationship between ERP and cardiac structure were then examined in a longitudinal subgroup (n=146) before and after a 90-day period of exercise training. ERP was defined as J-point elevation ≥0.1 mV in at least 2 leads within a nonanterior territory (inferior [II, III, aVF] or lateral territory [I, aVL, V4-V6]). Nonanterior ERP was present in 25.1% (221/879) of athletes, including the inferior subtype in 3.8% (33/879). Exercise training led to significant increases in the prevalence of ERP and the inferior subtype, but there were no associations between ERP and echocardiographic measures of left ventricular remodeling. In a multivariable model, ERP was associated with black race (odds ratio [OR], 5.84; 95% CI, 3.54 to 9.61; P <0.001), increased QRS voltage (OR, 2.08; 95% CI, 1.71 to 2.52; P <0.001), and slower heart rate (OR, 1.54; 95% CI, 1.26 to 1.87; P <0.001). Conclusions— Nonanterior ERP, including the inferior subtype, is common and has strong clinical associations among competitive athletes. The finding of increased ERP prevalence after intense physical training establishes a strong association between exercise and ERP.Background— Inferior lead early repolarization pattern (ERP) recently has been associated with sudden cardiac death. Although ERP is common among athletes, prevalence, ECG lead distribution, clinical characteristics, and effects of physical training remain uncertain. We sought to examine the nonanterior ERP in competitive athletes. Methods and Results— ERP was assessed in a cross-sectional cohort of collegiate athletes (n=879). The relationship between ERP and cardiac structure were then examined in a longitudinal subgroup (n=146) before and after a 90-day period of exercise training. ERP was defined as J-point elevation ≥0.1 mV in at least 2 leads within a nonanterior territory (inferior [II, III, aVF] or lateral territory [I, aVL, V4-V6]). Nonanterior ERP was present in 25.1% (221/879) of athletes, including the inferior subtype in 3.8% (33/879). Exercise training led to significant increases in the prevalence of ERP and the inferior subtype, but there were no associations between ERP and echocardiographic measures of left ventricular remodeling. In a multivariable model, ERP was associated with black race (odds ratio [OR], 5.84; 95% CI, 3.54 to 9.61; P<0.001), increased QRS voltage (OR, 2.08; 95% CI, 1.71 to 2.52; P<0.001), and slower heart rate (OR, 1.54; 95% CI, 1.26 to 1.87; P<0.001). Conclusions— Nonanterior ERP, including the inferior subtype, is common and has strong clinical associations among competitive athletes. The finding of increased ERP prevalence after intense physical training establishes a strong association between exercise and ERP.

The Impact of Endurance Exercise Training on Left Ventricular Torsion

OBJECTIVES We sought to examine the effect of endurance exercise training (EET) on peak systolic left ventricular torsion (LVT) and peak early diastolic untwisting rate (UTR). BACKGROUND Left ventricular (LV) structural adaptations to EET have been well characterized. LVT, a recognized marker of LV function in numerous cardiac diseases, has recently been investigated in the setting of exercise. However, longitudinal data characterizing the impact of sustained exercise training on LVT have not been reported. METHODS A prospective, longitudinal study design examined the impact of a 90-day period of training on LV twist mechanics in university male rowers (n = 15, mean age 18.6 ± 0.5 years). Conventional LV structural measurements, LV apical and basal rotation, peak systolic LVT, and peak early diastolic UTR were measured by 2-dimensional and speckle tracking echocardiography before and after the EET study period. RESULTS Participants experienced LV eccentric hypertrophy, characterized by increased LV end-diastolic volume (80.8 ± 8.7 ml/m(2) vs. 91.3 ± 8.0 ml/m(2), p < 0.001) and LV mass (101.3 ± 11.4 g/m(2) vs. 115.7 ± 12.6 g/m(2), p = 0.001). There was a significant increase in peak systolic apical rotation (8.9 ± 4.2° vs. 12.7 ± 3.9°, p = 0.002) but no change in basal rotation. This translated into a highly significant increase in peak systolic LVT after EET (14.1 ± 5.0° vs. 18.0 ± 3.6°, p = 0.002). The impact of EET on LV twist mechanics was not confined to ventricular systole, as peak early diastolic UTR (-110.6 ± 41.8°/s vs. -148.0 ± 29.8°/s, p = 0.003) and the percentage of untwisting that occurred by the end of isovolumic relaxation (31.2 ± 12.0% vs. 39.9 ± 14.9%, p = 0.04) increased. CONCLUSIONS Participation in EET was associated with significant changes in LV twist mechanics characterized by increased apical rotation, LVT, and UTR. These findings suggest that LVT and UTR augmentation may be an important and previously unrecognized component of exercise-induced cardiac remodeling.