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Cardiomyopathies represent a heterogeneous group of heart muscle diseases that are a major cause of morbidity and mortality. Classification schemes for cardiomyopathy have been complex, and efforts have been made to classify the disease states based on myocardial characteristics and etiologies. The etiology, diagnosis, and management of dilated cardiomyopathy (DCM), restrictive/infiltrative cardiomyopathy, and hypertrophic cardiomyopathy (HCM) are the subject of this chapter and several features of each form of cardiomyopathy are highlighted in Table 17-1.

Aims Galectin-3 is a prognostic heart failure (HF) biomarker that may mediate cardiac fibrosis. We examined the value of serial galectin-3 measurement for prognosis and response to therapy in chronic HF. Methods and results A total of 151 subjects with LV systolic dysfunction (LVSD) were followed through 908 visits over 10 ± 3 months. The amount of time spent with a galectin-3 level ≤ 20.0 ng/mL and changes between baseline and subsequent values were considered across visits, and used to assess risk for adverse cardiovascular (CV) events and associations with LV remodelling. Medication effects on galectin-3 were examined. Median galectin-3 values at baseline, 3 months, and 6 months were higher in patients with CV events (21.7 vs. 18.4 ng/mL, P = 0.03; 21.7 vs. 16.5 ng/mL, P = 0.03; 23.2 vs. 16.0 ng/mL, P = 0.007). Galectin-3 concentration changed in 35.2% of subjects during study procedures; time spent at ≤ 20.0 ng/mL was significantly associated with a lower rate of CV events, independently predicted fewer CV events even adjusted for relevant variables including study allocation, NT-proBNP, and renal function [odds ratio (OR) = 0.90; P = 0.05], and predicted increase in LV ejection fraction (OR = 1.20; P = 0.04). Serial galectin-3 measurement at 6 months added prognostic value beyond the baseline level (P = 0.02). There were no significant effects of medications on galectin-3 levels. Conclusion In chronic HF due to LVSD, serial galectin-3 measurement adds incremental prognostic information and predicts LV remodelling. In this study, HF therapies had no clear effects on galectin-3 levels.

Aims We sought to determine if heart failure (HF) care with a goal to lower N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations, compared with standard of care (SOC) management, is associated with improvement in echocardiographic parameters of cardiac structure and function. Methods and results Of 151 subjects with HF due to left ventricular systolic dysfunction (LVSD) prospectively randomized to NT-proBNP-guided vs. SOC HF care, 116 had serial echocardiographic data. Endpoints in this echocardiographic study included the relationship between change in NT-proBNP and LV reverse remodelling, as well as associations between biomarker-guided therapy and measures of diastolic function, right ventricular (RV) size and function, estimates of LV filling pressure and RV systolic pressure (RVSP), and the degree of mitral regurgitation (MR). After a mean of 10 months of study procedures, in adjusted analyses, final NT-proBNP concentrations predicted risk of remodelling [hazard ratio (HR) LV end-diastolic volume index = 1.43, 95% confidence interval (CI) 1.10–1.86, P = 0.007; HR LV end-systolic volume index = 1.54, 95% CI 1.10–1.91, P = 0.01; HR LV ejection fraction (LVEF) = 1.53, 905% CI 1.12–1.89, P = 0.02]. In addition to greater improvement in LVEF and reductions in LV volume, compared with SOC, NT-proBNP-guided patients showed significant decreases in the ratio of early transmitral peak velocity to early diastolic peak annular velocity (E/E'), pulmonary vein peak S velocity, RV fractional area change, RVSP, and MR severity. Conclusion NT-proBNP concentrations may serve as a non-invasive indicator of the state of cardiac structure and function in HF due to LVSD. Multiple, prognostically meaningful echocardiographic variables improved more significantly in patients treated with NT-proBNP-guided care vs. SOC. Trial registration: NCT00351390.

Importance Appropriate use criteria–based educational initiatives have been shown to improve transthoracic echocardiography (TTE) ordering practices of physicians in training. Whether such an intervention is successful with attending cardiologists remains unknown. Objective To prospectively investigate the effect of an appropriate use criteria–based educational intervention on ordering of outpatient TTEs by attending academic cardiologists. Design, Setting, and Participants We conducted a prospective, randomized clinical trial of an educational intervention designed to reduce the number of outpatient TTEs that were deemed to be rarely appropriate by published appropriate use criteria. Investigators classifying TTEs were blinded to participant groupings. The study was conducted within the cardiology division at the Massachusetts General Hospital, an academic quaternary care hospital. Staff members of the cardiology division were included; 66 cardiologists were randomized. The study was conducted from November 19, 2013, to June 1, 2014. An analysis of the evaluable population was performed. Interventions The appropriate use criteria–based educational intervention consisted of a review lecture and electronic information card, as well as monthly individual physician feedback via email. The email described the percentage of rarely appropriate TTEs as well as the appropriate use criteria rationale for classifying studies as rarely appropriate. Main Outcomes and Measures We hypothesized a priori that the educational intervention would reduce the number of rarely appropriate TTEs. The primary outcome was the rate of rarely appropriate TTEs. Results Of the 66 cardiologists enrolled in the study, 65 were included in the analysis (1 intervention cardiologist retired from practice during the study). The participants’ mean (SD) age was 50.6 (10.5) years; 48 (73%) were men. Following intervention, the proportion of rarely appropriate TTEs was significantly lower in the intervention vs control group (143 of 1359 [10.5%] vs 285 of 1728 [16.5%]; odds ratio [OR], 0.59 [95% CI, 0.39-0.88]; P = .01), and there was a nonsignificant increase in the proportion of appropriate TTEs in the intervention vs control group (1054 [77.6%] vs 1244 [72.0%]; OR, 1.38 [95% CI, 0.93-2.05]; P = .11). The most common of the 428 rarely appropriate indications were routine surveillance within 3 years after prosthetic valve insertion (73 [17.1%]), routine surveillance within 1 year for moderate or severe valvular stenosis (64 [15.0%]), and routine surveillance of cardiomyopathy (45 [10.5%]) or ventricular function (36 [8.4%]). Conclusions and Relevance An appropriate use criteria–based educational and feedback intervention reduced the number of rarely appropriate TTEs ordered by attending academic cardiologists. This strategy may be feasible to improve TTE utilization among cardiologists, and this type of intervention warrants study in other practice environments. Trial Registration clinicalrials.gov Identifier:NCT01968642

Syncope is a common reason for referral to pediatric cardiologists and to perform transthoracic echocardiography (TTE). We studied the applicability of pediatric appropriate use criteria (AUC) on initial outpatient evaluation of children with syncope before and after the release of the AUC document

Coronary CT angiography (CCTA) is an established tool for evaluation of low- to intermediate-risk emergency department (ED) patients with acute chest pain. We evaluated the medical management of patients diagnosed with previously unknown non-obstructive coronary artery disease (CAD) in the ED. The

Many proven heart failure (HF) therapies decrease N-terminal pro B-type natriuretic peptide (NT-proBNP) values over time, yet some patients have an NT-proBNP >1000 pg/mL following treatment, which is associated with poor outcomes. A total of 151 patients with left ventricular systolic dysfunction were treated with aggressive HF therapy in the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Clinical characteristics and NT-proBNP were measured at each visit during 10 months. In this post hoc analysis, biomarker nonresponse was defined as an NT-proBNP >1000 pg/mL and its relationship with echocardiographic and clinical characteristics and outcomes were explored. A risk model predictive of nonresponse was derived and externally validated. A rising NT-proBNP over time was associated with increased cardiovascular event rates while a decreasing NT-proBNP was associated with better clinical outcomes (58.2% vs 27.6%, P=.001). A higher percentage of time in biomarker response was associated with lower event rates (P

Left ventricular (LV) rotation occurs due to contraction of obliquely oriented myocardial fibres. Left ventricular twist (LVT) results from rotation of the apex and base in opposite directions. Although LVT is altered in various cardiac diseases, physiological factors that affect LVT remain incompletely understood. Isometric handgrip testing (IHGT), a well-established laboratory-based technique to increase LV afterload, was performed for 3 min at 40% maximum force generation in healthy human subjects (n = 18, mean age 29.7 ± 2.7 years). Speckle-tracking echocardiography was used to measure LV volumes, LV apical and basal rotation, peak systolic LVT and peak early diastolic untwisting rate (UTR) at rest and at peak IHGT. IHGT led to significant increase in systemic blood pressure (systolic, 120.6 ± 9.7 vs. 155.6 ± 14.5 mmHg, P < 0.001; diastolic, 67.5 ± 6.4 vs. 94.1 ± 21.1 mmHg, P < 0.001) and LV end-systolic volume (44.2 ± 7.8 vs. 50.5 ± 10.8 ml, P = 0.005), as well as a significant increase in heart rate (62.8 ± 11.7 vs. 84.7 ± 13.8 beats min−1; P < 0.001). IHGT produced a significant acute reduction in LV stroke volume (63.9 ± 12.0 vs. 49.4 ± 7.8 ml, P < 0.001). In this setting, there was a significant decrease in peak systolic apical rotation (11.9 ± 3.0 vs. 8.6 ± 2.2 deg, P < 0.001) and a resultant 25% decrease in peak systolic LVT (16.6 ± 2.8 vs. 12.5 ± 2.8 deg, P < 0.001). The magnitude of peak early diastolic UTR did not change (−114.5 ± 26.4 vs. −110.6 ± 39.8 deg s−1, P = 0.71). Peak systolic apical rotation and LVT decrease during IHGT in healthy humans. This impairment of LV twist mechanics may in part underlie the LV dysfunction that can occur in the clinical context of acute increase in afterload.

The 2008 appropriate use criteria (AUC) for stress echocardiographic (SE) examinations were revised in 2011 to cover a wider range of scenarios of use. Data comparing the 2008 and 2011 AUC for SE are limited.A retrospective chart review of SE studies performed at an academic medical center was conducted, and ordering of SE studies was assessed using the 2008 and 2011 AUC.A total of 252 consecutive SE studies performed in 2011 were reviewed. The 2008 AUC classified 126 SE studies (50%), and the 2011 AUC classified 221 SE studies (88%) (P.001). Of all SE studies, 106 (42%) were performed as part of evaluations for noncardiac solid-organ transplantation. The majority of these studies (79%) were classified as inappropriate using the 2011 AUC and were not classifiable using the 2008 AUC. Of the 146 SE studies performed for other reasons, 69% were appropriate and 22% were inappropriate using the 2011 AUC. Inappropriate SE studies for both the general nontransplant and noncardiac solid-organ transplantation populations were nearly exclusively ordered for perioperative assessment with normal functional capacity. The SE studies that remained unclassified by the 2011 AUC were related to the assessment of specialized cardiac conditions, including hypertrophic cardiomyopathy and follow-up after heart transplantation.The 2011 AUC classify a significantly greater proportion of SE studies compared with the 2008 AUC. Most of the reclassified SE studies using the 2011 AUC were inappropriate and were ordered for perioperative assessments in patients with normal functional capacity.

Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes.

Elderly patients with heart failure (HF) have a worse prognosis than younger patients. We wished to study whether elders benefit from natriuretic peptide-guided HF care in this single-center study.A total of 151 patients with HF resulting from left ventricular systolic dysfunction (LVSD) were treated with HF treatment by standard-of-care (SOC) management or guided by N-terminal pro-B type natriuretic peptide (NT-proBNP) values (with a goal to lower NT-proBNP ≤1000 pg/mL) over 10 months. The primary end point for this post-hoc analysis was total cardiovascular events in 2 age categories (75 and ≥75 years). In those ≥75 years of age (n = 38), NT-proBNP values increased in the SOC arm (2570 to 3523 pg/mL, P = .01), but decreased in the NT-proBNP-guided arm (2664 to 1418 pg/mL, P = .001). Elderly patients treated with SOC management had the highest rate of cardiovascular events, whereas the elderly with NT-proBNP management had the lowest rate of cardiovascular events (1.76 events per patient versus 0.71 events per patient, P = .03); the adjusted logistic odds for cardiovascular events related to NT-proBNP-guided care for elders was 0.24 (P = .008), whereas in those75 years (n = 113), the adjusted logistic odds for events following NT-proBNP-guided care was 0.61 (P = .10).Natriuretic peptide-guided HF care was well tolerated and resulted in substantial improvement in cardiovascular event rates in elders (ClinicalTrials.Gov #00351390).

The reduction in the size of full-capability echocardiographic machines facilitates "out-of-hospital" transthoracic echocardiography (TTE). Data documenting the feasibility, yield, and logistical considerations of out-of-hospital TTE for preparticipation evaluation of athletes are sparse.A multiyear study was conducted to examine the role of 12-lead electrocardiography for athlete screening in which TTE was used to document or exclude underlying structural heart disease. Using a commercially available portable transthoracic echocardiographic system, the rate of technically adequate imaging, diagnostic yield, and the time required for the completion of TTE (including setup, performance, and interpretation) were examined. TTE was performed in university medical offices and at "out-of-office" athletic facilities. Measurements were recorded during each year of the study to determine the impact of targeted attempts to improve efficiency.Four hundred sixty-seven of 510 participants had transthoracic echocardiographic images that were technically adequate for complete interpretation (imaging success rate, 92%). Echocardiographic evidence of physiologic, exercise-induced cardiac remodeling was observed in 110 of 510 (22%). Cardiac abnormalities with relevance to sports participation risk were detected in 11 of 508 participants (2.2%). Over 3 years, the average time for the completion of TTE (including setup, imaging, and interpretation) decreased (year 1, 17.4 ± 3 min; year 2, 14.0 ± 2.1 min; year 3, 11.0 ± 1.8 min; P.001). This was driven by a significant decrease in the time required for TTE at out-of-office athletic facilities.Community-based TTE in athletes is feasible and is associated with a high rate of technically adequate imaging. Importantly, there appears to be a significant learning curve associated with out-of-hospital TTE.

Information about a real patient is presented in stages (boldface type) to an expert clinician (Dr Michael A. Fifer), who responds to the information, sharing his reasoning with the reader (regular type). A Discussion by the authors follows. A 76-year-old man with a history of hypertrophic obstructive cardiomyopathy (HOCM), hypertension, dyslipidemia, and obstructive sleep apnea presents with dyspnea on exertion. This symptom has progressed slowly over the past year, to the point that he now has dyspnea on climbing 1 flight of stairs. The patient denies orthopnea, paroxysmal nocturnal dyspnea, edema, chest discomfort, palpitations, lightheadedness, and syncope. His medications are metoprolol, verapamil, disopyramide, rosuvastatin, and omeprazole. He is a retired electrician, is married with 3 adult children, and lives in Florida and Massachusetts, each for half the year. He has a history of heavy tobacco use but quit smoking more than 30 years ago. His family history is notable only for diabetes mellitus and stroke in his father; there are no family members with heart failure, hypertrophic cardiomyopathy (HCM), or sudden cardiac death (SCD). Dr Michael A. Fifer: This patient's presenting complaint is progressive dyspnea on exertion, for which he has possibly contributory comorbidities, namely, obstructive sleep apnea and hypertension. The history of HCM is particularly relevant because dyspnea is a common initial manifestation of the disease.1 Dyspnea may occur in HCM as a result of a variety of mechanisms, including diastolic heart failure due to myocardial hypertrophy and fibrosis, left ventricular outflow tract (LVOT) obstruction, and associated mitral regurgitation (MR). Although the correlation between symptoms and the magnitude of the LVOT gradient is weak,2 dyspnea is usually relieved by septal reduction therapy. In this patient, any or all of these factors might contribute to progressive dyspnea on exertion. More information regarding how the diagnosis of HOCM was …

MicroRNAs (miRNAs) are intracellular mediators of essential biological functions. Recently, plasma-based 'circulating' miRNAs (c-miRNAs) have been shown to control cellular processes, but the c-miRNA response to human exercise remains unknown. We sought to determine whether c-miRNAs are dynamically regulated in response to acute exhaustive cycling exercise and sustained rowing exercise training using a longitudinal, repeated measures study design. Specifically, c-miRNAs involved in angiogenesis (miR-20a, miR-210, miR-221, miR-222, miR-328), inflammation (miR-21, miR-146a), skeletal and cardiac muscle contractility (miR-21, miR-133a), and hypoxia/ischaemia adaptation (miR-21, miR-146a, and miR-210) were measured at rest and immediately following acute exhaustive cycling exercise in competitive male rowers (n = 10, age = 19.1 ± 0.6 years) before and after a 90 day period of rowing training. Distinct patterns of c-miRNA response to exercise were observed and adhered to four major profiles: (1) c-miRNA up-regulated by acute exercise before and after sustained training (miR-146a and miR-222), (2) c-miRNA responsive to acute exercise before but not after sustained training (miR-21 and miR-221), (3) c-miRNA responsive only to sustained training (miR-20a), and (4) non-responsive c-miRNA (miR-133a, miR-210, miR-328). Linear correlations were observed between peak exercise levels of miR-146a and VO2max (r = 0.63, P = 0.003) and between changes in resting miR-20a and changes in VO2max (pre-training vs. post-training, r = 0.73; P = 0.02). Although future work is required, these results suggest the potential value of c-miRNAs as exercise biomarkers and their possible roles as physiological mediators of exercise-induced cardiovascular adaptation.

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.

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.

UNLABELLED: There is significant individual variability in the cardiac adaptation that occurs in response to exercise training. Factors associated with this variability remain incompletely understood. To date, the relationship between the competition level at which athletes participate and their underlying cardiac parameters has not been explored. PURPOSE: The purpose of this study was to determine whether parameters of cardiac structure and function differ significantly among elite competitive rowers (ER), subelite competitive rowers (SR), and sedentary controls (C). METHODS: Cardiac parameters were assessed in ER (n = 20), SR (n = 20), and C (n = 20) using two-dimensional, tissue Doppler, and speckled-tracking echocardiography. RESULTS: Physiologic cardiac remodeling was present in both ER and SR as evidenced by the significant differences in the majority of structural and functional parameters in both rower groups when compared with C. When compared with SR, ER were found to have greater left ventricular (LV) end-diastolic volume (76 +/- 6 vs 71 +/- 8 mL x m(-2), P = 0.02), LV mass (150 +/- 11 vs 134 +/- 16 g x m(-2), P = 0.002), and right ventricular (RV) end-diastolic chamber dimensions (15.6 +/- 0.9 vs 13.9 +/- 1.5 cm(2) x m(-2), P < 0.001). Further, ER demonstrated significantly more enhancement of RV systolic function (peak strain = 36% +/- 7% vs 31% +/- 6%, P = 0.008) and late diastolic relaxation in both the LV (A' = 4.2 +/- 1.3 vs 3.2 +/- 0.9 cm x s(-1), P = 0.01) and the RV (A' = 6.6 +/- 1.4 vs 4.3 +/- 1.3 cm x s(-1), P < 0.001). CONCLUSIONS: Although cardiac remodeling occurs in both ER and SR, specific aspects of cardiac structure and function differ between rowers who compete at the elite and the subelite levels of sport.

A 19-year-old healthy woman presented with new onset of severe migrainous headache. She did not take medications or use illicit drugs. There was no personal or family history of hypertension. Physical examination revealed a blood pressure of 220/130 mm Hg in both arms. There was no fourth heart sound. She had full and symmetric pulses in the upper and lower extremities with no radial/femoral delay. There were no carotid, subclavian, or abdominal bruits. Fundoscopic examination revealed normal retinal arteries without hypertensive retinopathy. Renal function and serum potassium were normal. Renal artery duplex ultrasonography revealed elevated peak systolic and end-diastolic velocities in the mid to distal portion of the right renal artery, consistent with severe right renal artery stenosis. The left renal artery was normal. The right kidney measured 8.8 cm with atrophy of the right cortical margin. The left kidney was 11.5 cm. There were normal renal resistive indexes …

Platelet adhesion, aggregation, and activation play a key role in initiating and propagating coronary thrombosis. This provides opportunities to pharmacologically interfere with platelet function and antiplatelet therapies are a central component in the treatment of acute coronary syndromes. Whether the reperfusion strategy for ST-segment elevation myocardial infarction (STEMI) is pharmacologic or catheter-based, the use of adjunctive antiplatelet therapy can reduce the rate of death and ischemic complications. Aspirin, an irreversible inhibitor of platelet cyclooxygenase 1, provides mortality benefit to STEMI patients and is a cornerstone of therapy. Thienopyridines inhibit platelet activation and aggregation by targeting the P2Y12 adenosine diphosphate (ADP) receptor and have been shown to provide mortality benefit in STEMI patients. Clopidogrel is preferred over ticlopidine due to a more favorable side effect profile. The Clopidogrel as Adjunctive Reperfusion Therapy – Thrombolysis in Myocardial Infarction 28 trial (CLARITY – TIMI 28) and the Clopidogrel and Metoprolol Infarction Trial/the Second Chinese Cardiac Study (COMMIT/CCS – 2) are two recent landmark trials demonstrating mortality benefit with clopidogrel in patients receiving pharmacologic reperfusion for STEMI. The glycoprotein (GP) IIb/IIIa receptor mediates platelet aggregation induced by all physiologic agonists and blockade of the receptor, either by monoclonal antibodies (abciximab) or by small molecules (eptifibatide and tirofiban), can be used in adjunctive treatment of STEMI, particularly in patients receiving primary percutaneous intervention (PCI). Novel antiplatelet agents, which may address issues relating to variability in response and irreversibility of inhibitor effects, are under active investigation and will better refine the role of antiplatelet therapy in this clinical setting and lead to further improvement in patient outcomes.

Recent studies have suggested that early repolarization (ER) might be associated with up to 1/3 of idiopathic ventricular tachycardia/ventricular fibrillation (VT/VF) cases ("malignant" ER). We sought to identify electrocardiographic features to distinguish benign from malignant variants of ER. We reviewed the medical records for implantable-cardioverter defibrillators implanted at a single institution (1988 to 2008) to identify cases of idiopathic VT/VF. The electrocardiograms were scored for ER, defined as a >or=0.1-mV elevation of the QRS-ST junction manifesting as J-point slurring or notching in 2 contiguous leads. We also identified a cohort of 200 healthy age- and gender-matched controls with electrocardiographic findings previously identified as normal ER ("benign" ER cohort). Of 1,224 consecutive implantable-cardioverter defibrillator implants, we identified 39 cases of idiopathic VT/VF. Of the 39 cases, 9 (23%) demonstrated ER. During a mean follow-up of 7.2 +/- 4.6 years, the combined end point of appropriate implantable-cardioverter defibrillator shocks or all-cause mortality occurred less frequently in cases of idiopathic VT/VF with ER than in those without ER (11% vs 30%, odds ratio 0.29, 95% confidence interval 0.03 to 2.69, p = 0.40). A comparison of the electrocardiograms between those with malignant ER and controls demonstrated that QRS notching was significantly more prevalent among cases when present in leads V4 (44% vs 5%, p = 0.001) and V5 (44% vs 8%, p = 0.006), with a similar trend in lead V6 (33% vs 5%, p = 0.013). In conclusion, left precordial terminal QRS notching is more prevalent in malignant variants of ER than in benign cases. These findings could have important implications for risk stratification of patients with ER.

Left ventricular (LV) hypertrophy is a well-established, but highly variable, finding among exercise-trained persons. The causes for the variability in LV remodeling in response to exercise training remain incompletely understood. The present study sought to determine whether a family history of hypertension is a determinant of the cardiac response to exercise training. The cardiac parameters in 60 collegiate rowers (30 men/30 women; age 19.8 +/- 1.1 years) with (family history positive [FH+], n = 22) and without (family history negative [FH-], n = 38) a FH of hypertension were studied with echocardiography before and after 90 days of rowing training. The LV mass increased significantly in both groups. However, the LV mass increased significantly more in FH- persons (Delta 17 +/- 5 g/m(2)) than in FH+ persons (Delta 9 +/- 6 g/m(2), p

This prospective, longitudinal study examined the effects of participation in team-based exercise training on cardiac structure and function. Competitive endurance athletes (EA, n = 40) and strength athletes (SA, n = 24) were studied with echocardiography at baseline and after 90 days of team training. Left ventricular (LV) mass increased by 11% in EA (116 ± 18 vs. 130 ± 19 g/m2; P < 0.001) and by 12% in SA (115 ± 14 vs. 132 ± 11 g/m2; P < 0.001; P value for the compared Δ = NS). EA experienced LV dilation (end-diastolic volume: 66.6 ± 10.0 vs. 74.7 ± 9.8 ml/m2, Δ = 8.0 ± 4.2 ml/m2; P < 0.001), enhanced diastolic function (lateral E ′: 10.9 ± 0.8 vs. 12.4 ± 0.9 cm/s, P < 0.001), and biatrial enlargement, while SA experience LV hypertrophy (posterior wall: 4.5 ± 0.5 vs. 5.2 ± 0.5 mm/m2, P < 0.001) and diminished diastolic function (E′ basal lateral LV: 11.6 ± 1.3 vs. 10.2 ± 1.4 cm/s, P < 0.001). Further, EA experienced right ventricular (RV) dilation (end-diastolic area: 1,460 ± 220 vs. 1,650 ± 200 mm/m2, P < 0.001) coupled with enhanced systolic and diastolic function (E′ basal RV: 10.3 ± 1.5 vs. 11.4 ± 1.7 cm/s, P < 0.001), while SA had no change in RV parameters. We conclude that participation in 90 days of competitive athletics produces significant training-specific changes in cardiac structure and function. EA develop biventricular dilation with enhanced diastolic function, while SA develop isolated, concentric left ventricular hypertrophy with diminished diastolic relaxation.

The international governing body for competitive rowing recently mandated the inclusion of 12-lead ECG during preparticipation screening. We therefore sought to describe normative ECG characteristics and to examine the prevalence of abnormal ECG findings as defined by contemporary athlete ECG interpretation criteria among competitive rowers.Competitive rowers (n=330, 56% male) underwent standard 12-lead ECG at the time of collegiate preparticipation screening. ECGs were analysed quantitatively to develop a sport-specific normative database and then for the presence of abnormalities in accordance with the 2010 European Society of Cardiology (ESC) recommendations and 2013 'Seattle Criteria.'94% of rowers had one or more training-related ECG patterns including sinus bradycardia (51%), sinus arrhythmia (55%), and incomplete right bundle branch block (42%). Males were more likely than females to have isolated voltage criteria for left ventricular hypertrophy (LVH) (51% vs 8%, p0.001) and early repolarisation pattern (76% vs 23%, p0.001). Application of the 2010 ESC criteria, compared to the Seattle criteria, resulted in the classification of a significantly greater number of abnormal ECGs (47% vs 4%; p0.001). The detection of true pathology, accomplished by both interpretation criteria, was confined to a single case of ventricular pre-excitation.Training-related ECG patterns with several gender-based differences are common among competitive rowers. The diagnostic accuracy and down-stream clinical implications of ECG-inclusive preparticipation screening among rowers will be dictated by the choice and future refinement of ECG interpretation criteria.

Exercise-induced cardiac remodelling (EICR) refers to changes in cardiac structure that occur in response to exercise training. Initial reports of cardiac enlargement in athletes date back to 1899 and subsequently numerous aspects of EICR, including ventricular chamber enlargement, myocardial hypertrophy, and atrial dilatation have been documented. Functional correlates of EICR are not as well characterized. Although global measures of left ventricular (LV) function, such as LV ejection fraction, are typically normal in athletes, recently developed advanced imaging techniques have begun to identify alterations in regional myocardial function that occur in response to exercise. Strain imaging, also known as deformational imaging, represents a technological advancement that has been developed to objectively quantify regional myocardial function. The term strain refers to the fractional change in length compared to the end-diastolic length, and three normal strains (longitudinal, circumferential and radial) can be assessed with speckle-tracking echocardiography. Additionally, due to the helical orientation of myofibres (left-handed helix in the subepicardium and right-handed helix in the subendocardium), myocardial contraction also produces transmural (i.e. shear) strains. The circumferential–longitudinal shear strain represents LV torsion, or the wringing motion of the heart, and results from counter-directional rotation of the LV base and apex. When viewed from an apical reference point, systolic rotation at the apex is counterclockwise and the base rotates in an overall clockwise direction. Regional myocardial function has only recently been investigated in the context of exercise training. In a longitudinal study of endurance trained athletes, we observed increases in normal strains following a 90 day period of endurance exercise training in young competitive rowers (Baggish et al. 2008). Interestingly, changes in circumferential strain showed regional heterogeneity characterized by relative dysfunction in the interventricular septum, likely resulting from concomitant right ventricular dilation. Cross-sectional reports have identified differences in LV torsion when comparing cyclists and sedentary controls (Nottin et al. 2008) and more recently a longitudinal study demonstrated changes in LV apical rotation and LV torsion after a period of endurance exercise training (Weiner et al. 2010). In a recent issue of The Journal of Physiology, Stohr et al. (2012) add to the literature by demonstrating differences in LV apical rotation and torsion (twist) in a group of individuals with high peak oxygen consumption () versus a group with moderate . Specifically, they show that for the same augmentation index (AIx), a non-invasive estimate of aortic stiffness and perhaps aorto-ventricular coupling, the high individuals had significantly lower apical rotation and torsion, both at rest and during submaximal exercise. Importantly, these changes in regional LV function were observed in the absence of differences in LV wall thickness and cavity size between the two groups. Two features of the results observed in the current study by Stohr et al. (2012) warrant emphasis. First, the finding that LV apical rotation was altered, and not LV basal rotation, is consistent with other myocardial deformation studies in athletes (Nottin et al. 2008; Weiner et al. 2010) and with the notion that the magnitude of apical counterclockwise rotation is the primary determinant of overall peak systolic LV torsion (Gibbons Kroeker et al. 1993). Although measurement of LV apical rotation requires careful standardization of the echocardiographic imaging plane (Weiner et al. 2010), its assessment is less time consuming than measuring LV torsion and can be made without significant software-based post-image acquisition processing. It is therefore possible that once normative values for LV apical rotation in human health and disease are established, it may become a surrogate marker of LV torsion and will be a useful marker of LV regional function. Second, the authors note dissociation between shear strain and normal strain as high aerobic fitness was associated with decreased apical rotation/torsion but circumferential and radial strain was not influenced by aerobic fitness level. Similar dissociation between LV torsion and normal strains has been observed in previous studies of heart stress (Stohr et al. 2011) and progressive submaximal exercise testing (Doucende et al. 2010). This highlights the complex nature of studying regional myocardial function and suggests a unique potential role for LV apical rotation as a marker of response to exercise training. To completely determine the physiological importance of EICR, investigators need to move beyond the study of LV function at rest. Specifically, evaluation of the myocardial response to acute haemodynamic perturbation or exercise challenge represents a required step to fully define the scope and relevance of EICR. Stohr et al. (2012) recognize this important concept as subjects in their study underwent submaximal exercise testing. Evaluation of the myocardial response to hemodynamic/exercise challenge, what we term functional myocardial profiling, may ultimately represent a method for characterizing exercise performance and also aid in the differentiation of physiological and pathological hypertrophy. For example, some forms of EICR (i.e. concentric hypertrophy in strength-trained athletes) may be difficult to distinguish from mild forms of pathological hypertrophy (i.e. hypertrophic cardiomyopathy). It is possible that defining the myocardial response to exercise challenge may produce unique myocardial profiles for these two entities, possibly obviating the need for more prolonged and intensive diagnostic manoeuvres such as prescribed detraining. Evaluation of regional myocardial function, including LV strain, rotation and torsion, holds promise to fully characterize the functional changes that accompany the well-defined structural features of EICR. Coupled with novel techniques that can investigate the molecular and cellular changes associated with EICR, the complete functional phenotype of EICR has the potential to be unlocked. Broad knowledge of the functional characteristics of EICR will assist clinical assessments of exercise performance and may ultimately help distinguish the athlete's heart from pathological forms of LV hypertrophy.

Stress echocardiography is a noninvasive cardiovascular diagnostic test that provides functional and hemodynamic information in the assessment of a number of cardiac diseases. Performing stress echocardiography with a pharmacologic agent such as dobutamine allows for simulation of increased heart rate and increased myocardial physiologic demands in patients who may be unable to exercise due to musculoskeletal or pulmonary comorbidities. Dobutamine stress echocardiography (DSE), like exercise echocardiography, has found its pri- mary application in ischemic heart disease, with roles in identification of obstructive epicardial coronary artery disease, detection of viable myocardium, and assessment of the efficacy of anti-ischemic medical therapy in patients with known coronary artery disease. DSE features prominently in the evaluation and management of valvular heart disease by helping to assess the effects of mitral and aortic stenoses, as well as a specific use in differentiating true severe valvular aortic stenosis from pseudostenosis that may occur in the setting of left ventricular systolic dysfunction. DSE is generally well tolerated, and its side effects and contraindica- tions generally relate to consequences of excess inotropic and/or chronotropic stimulation of the heart. The aim of this paper is to review the indications, contraindications, advantages, disadvantages, and risks of DSE.

The term “endurance sport (ES)” is broadly used to characterize any exercise that requires maintainence of high cardiac output over extended time. However, the relative amount of dynamic (volume) vs. static (pressure) cardiac stress varies across ES disciplines. We sought to determine if high

H. Tristram Engelhardt, Jr., in his The Foundations of Bioethics, constructs what he calls the foundations of a “general secular morality”1 of bioethics. “This account,” he explains, “can be regarded as a transcendental argument to justify a principle of freedom as a side constraint, as a source of [moral] authority” (70).2 This principle, which he calls the principle of permission (or forbearance), justifies a basic moral right against the use of unconsented-to force against the innocent (15). But it does not justify a basic moral right to assistance, including access to basic health care. “A basic human secular moral right to health care,” Engelhardt explains, “does not exist-not even to a decent minimum of health care” (375). However, he argues, if a moral community chooses to do so, it may create a right to basic health care by establishing at least a two-tiered health care system: an upper tier where personsuse private funds to purchase whatever medical care they wish, and a bottom tier where persons have access regardless of their ability to pay. The principle of permission and its derivative principle of private ownership justify the upper tier, which is universally required as a basic right, while a principle of beneficence justifies a bottom tier, which is always optional.

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.

ObjectivesThis study sought to prospectively study the impact of an appropriate use criteria (AUC)-based educational intervention on transthoracic echocardiography (TTE) ordering among house staff on the inpatient general internal medicine service at an academic medical center.BackgroundAUC for TTE were developed in response to concerns about inappropriate use of TTE. To date, educational interventions based on the AUC to reduce inappropriate use of TTE have not been prospectively studied.MethodsA prospective, time series analysis of an educational intervention was conducted and then compared with TTE ordering on the same medical service during a control period. The intervention consisted of: 1) a lecture to house staff on the 2011 AUC for TTE; 2) a pocket card that applied the AUC to common clinical scenarios; and 3) biweekly e-mail feedback regarding ordering behavior. TTE ordering was tracked over the intervention period on a daily basis and feedback reports were e-mailed at 2-week intervals. The primary outcome was the proportion of inappropriate and appropriate TTE ordered during the intervention period.ResultsOf all TTEs ordered in the control and study periods, 99% and 98%, respectively, were classifiable using the 2011 AUC. During the study period, there was a 26% reduction in the number of TTE ordered per day compared with the number ordered during the control period (2.9 vs. 3.9 TTE, p < 0.001). During the study period, the proportion of inappropriate TTE was significantly lower (5% vs. 13%, p < 0.001) and the proportion of appropriate TTE was significantly higher (93% vs. 84%, p < 0.001).ConclusionsA simple educational intervention produced a significant reduction in the proportion of inappropriate TTE and increased the proportion of appropriate TTE ordered on an inpatient academic medical service. This study provides a practical approach for using the AUC to reduce the number of inappropriate TTE. Further study in other practice environments is warranted.

ObjectivesWe sought to examine the effect of endurance exercise training (EET) on peak systolic left ventricular torsion (LVT) and peak early diastolic untwisting rate (UTR).BackgroundLeft 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.MethodsA 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.ResultsParticipants experienced LV eccentric hypertrophy, characterized by increased LV end-diastolic volume (80.8 ± 8.7 ml/m2 vs. 91.3 ± 8.0 ml/m2, p < 0.001) and LV mass (101.3 ± 11.4 g/m2 vs. 115.7 ± 12.6 g/m2, 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.ConclusionsParticipation 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.

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 )