Meagan M. Wasfy

Exercise Dose in Clinical Practice

There is wide variability in the physical activity patterns of the patients in contemporary clinical cardiovascular practice. This review is designed to address the impact of exercise dose on key cardiovascular risk factors and on mortality. We begin by examining the body of literature that supports a dose-response relationship between exercise and cardiovascular disease risk factors, including plasma lipids, hypertension, diabetes mellitus, and obesity. We next explore the relationship between exercise dose and mortality by reviewing the relevant epidemiological literature underlying current physical activity guideline recommendations. We then expand this discussion to critically examine recent data pertaining to the impact of exercise dose at the lowest and highest ends of the spectrum. Finally, we provide a framework for how the key concepts of exercise dose can be integrated into clinical practice.

myosin 7aa(-/-) mutant zebrafish show mild photoreceptor degeneration and reduced electroretinographic responses.

Mutations in myosin VIIa (MYO7A) cause Usher Syndrome 1B (USH1B), a disease characterized by the combination of sensorineural hearing loss and visual impairment termed retinitis pigmentosa (RP). Although the shaker-1 mouse model of USH1B exists, only minor defects in the retina have been observed during its lifespan. Previous studies of the zebrafish mariner mutant, which also carries a mutation in myo7aa, revealed balance and hearing defects in the mutants but the retinal phenotype has not been described. We found elevated cell death in the outer nuclear layer (ONL) of myo7aa(-/-) mutants. While myo7aa(-/-) mutants retained visual behaviors in the optokinetic reflex (OKR) assay, electroretinogram (ERG) recordings revealed a significant decrease in both a- and b-wave amplitudes in mutant animals, but not a change in ERG threshold sensitivity. Immunohistochemistry showed mislocalization of rod and blue cone opsins and reduced expression of rod-specific markers in the myo7aa(-/-) ONL, providing further evidence that the photoreceptor degeneration observed represents the initial stages of the RP. Further, constant light exposure resulted in widespread photoreceptor degeneration and the appearance of large holes in the retinal pigment epithelium (RPE). No differences were observed in the retinomotor movements of the photoreceptors or in melanosome migration within the RPE, suggesting that myo7aa(-/-) does not function in these processes in teleosts. These results indicate that the zebrafish myo7aa(-/-) mutant is a useful animal model for the RP seen in humans with USH1B.

Exercise-Induced Left Ventricular Remodeling Among Competitive Athletes A Phasic Phenomenon

Background—Contemporary understanding of exercise-induced cardiac remodeling is based on cross-sectional data and relatively short duration longitudinal studies. Temporal progression of exercise-induced cardiac remodeling remains incompletely understood. Methods and Results—A longitudinal repeated-measures study design using 2-dimensional and speckle-tracking echocardiography was used to examine acute augmentation phase (AAP; 90 days) and more extended chronic maintenance phase (39 months) left ventricular (LV) structural and functional adaptations to endurance exercise training among competitive male rowers (n=12; age 18.6±0.5 years). LV mass was within normal limits at baseline (93±9 g/m2), increased after AAP (105±7 g/m2; P=0.001), and further increased after chronic maintenance phase (113±10 g/m2; P<0.001 for comparison to post-AAP). AAP LV hypertrophy was driven by LV dilation (&Dgr;LV end-diastolic volume, 9±3 mL/m2; P=0.004) with stable LV wall thickness (&Dgr;LV wall thickness, 0.3±0.1 mm; P=0.63). In contrast, chronic maintenance phase LV hypertrophy was attributable to LV wall thickening (&Dgr; LV wall thickness, 1.1±0.4 mm; P=0.004) with stable LV chamber volumes (&Dgr;LV end-diastolic volume, 1±1 mL/m2; P=0.48). Early diastolic peak tissue velocity increased during AAP (−11.7±1.9 versus −13.6±1.3 cm/s; P<0.001) and remained similarly increased after chronic maintenance phase. Conclusions—In a small sample of competitive endurance athletes, exercise-induced cardiac remodeling follows a phasic response with increases in LV chamber size, early diastolic function, and systolic twist in an acute augmentation phase of exercise training. This is followed by a chronic phase of adaptation characterized by increasing wall thickness and regression in LV twist. Training duration is a determinant of exercise-induced cardiac remodeling and has implications for the assessment of myocardial structure and function in athletes.

Differentiating the athleteʼs heart from hypertrophic cardiomyopathy

Purpose of review Exercise-induced cardiac remodeling (EICR), or athletes heart, refers to the cardiac structural and functional adaptations to exercise training. Although the degree of physiological left ventricular hypertrophy (LVH) is typically mild in trained athletes, in some LVH is substantial enough to prompt concern for hypertrophic cardiomyopathy (HCM). This review summarizes the available imaging tools to help make this important clinical distinction. Recent findings Advanced echocardiographic techniques (tissue and Doppler and speckle tracking) and cardiac magnetic resonance imaging are being investigated to aid in the differentiation of EICR and HCM in ‘gray-zone’ hypertrophy cases. Higher early diastolic (E′) velocity by tissue Doppler imaging has been documented in athletes. HCM patients have been found to have lower global longitudinal strain (GLS) when compared with athletes with LVH. Analysis of twisting and untwisting of the LV with speckle tracking may also help distinguish athletes heart from HCM. Studies of the expected degree and time course of LVH regression after exercise cessation (in the setting of prescribed detraining) are needed as this may be a useful adjunct to determine the cause of LVH in particularly challenging cases. Summary Ongoing research with novel imaging techniques continues to improve the ability to distinguish athletes heart from HCM in situations of ‘gray-zone’ hypertrophy.

Cardiovascular Risk and Disease Among Masters Endurance Athletes: Insights from the Boston MASTER (Masters Athletes Survey To Evaluate Risk) Initiative

Masters athletes (MAs), people over the age of 35 that participate in competitive sports, are a rapidly growing population that may be uniquely at risk for cardiovascular (CV) disease. The objective of this study was to develop a comprehensive clinical CV profile of MA. An electronic Internet-based survey (survey response rate = 66 %) was used to characterize a community cohort of MAs residing in Eastern Massachusetts, USA. Clinical and lifestyle factors associated with prevalent CV disease were determined using logistic regression. Among 591 MAs (66 % men, age = 50 ± 9 years) with 21.3 ± 5.5 years of competitive endurance sport exposure, at least one CV risk factor was present in 64 % including the following: family history of premature atherosclerosis (32 %), prior/current tobacco exposure (23 %), hypertension (12.0 %), and dyslipidemia (7.4 %). There was a 9 % (54/591) prevalence of established CV disease which was accounted for largely by atrial fibrillation (AF) and coronary atherosclerosis (CAD). Prevalent AF was associated with years of exercise exposure [adjusted odds ratio, OR (95 % confidence intervals); OR = 1.10 (1.06, 1.21)] and hypertension [OR = 1.05 (1.01, 1.10)] while CAD was associated with dyslipidemia [OR = 9.09 (2.40, 34.39)] and tobacco use [OR = 1.78 (1.34, 3.10)] but was independent of exercise exposure. Among MAs, AF is associated with prior exercise exposure whereas CAD is associated with typical risk factors including dyslipidemia and prior tobacco use. These findings suggest that there are numerous opportunities to improve disease prevention and clinical care in this population.

Sudden Cardiac Death in Athletes.

There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed.

Multimodality imaging of spontaneous coronary artery dissection: case studies of the Massachusetts General Hospital.

A 57-year-old woman presented to an outside hospital with sudden onset anginal pain at rest, radiating to the left arm. Initial ECG showed ST elevations in the anterior leads. Her pain improved but did not resolve with nitroglycerin and aspirin. Emergent invasive coronary angiography revealed abrupt narrowing and diffuse irregularity of the distal left anterior descending, which did not improve with intracoronary nitroglycerin and nicardipine. At the time, the etiology of the event was uncertain, and treatment for a possible thrombotic coronary event was initiated with dual antiplatelet therapy, statin, angiotensin-converting enzyme inhibitor, and βblockade. Serum troponin peaked at 22.5 ng/ml. Two months later, she was referred to our hospital for further evaluation at which time a coronary computed tomography angiography (CTA) was requested.

Aortic valve replacement associated with survival in severe regurgitation and low ejection fraction

Objectives Although guidelines support aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR) and left ventricular ejection fraction (LVEF) <50%, severe left ventricular dysfunction (LVEF <35%) is thought to confer high surgical risk. We sought to determine if a survival benefit exists with AVR compared with medical management in this high-risk, relatively rare population. Methods A large institutional echocardiography database was queried to identify patients with severe AR and LVEF <35%. Manual chart review was performed. Due to small sample size and population heterogeneity, corrected group prognosis method was applied, which calculates the adjusted survival curve for each individual using fitted Cox proportional hazard model. Average survival adjusted for comorbidities and age was then calculated using the weighted average of the individual survival curves. Results Initially, 2 54 614 echocardiograms were considered, representing 1 45 785 unique patients, of which 40 patients met inclusion criteria. Of those, 18 (45.0%) underwent AVR and 22 (55.0%) were managed medically. Absolute mortality was 27.8% in the AVR group and 91.2% in the medical management group. After multivariate adjustment, end-stage renal disease (HR=17.633, p=0.0335) and peripheral arterial disease (HR=6.050, p=0.0180) were associated with higher mortality. AVR was associated with lower mortality (HR=0.143, p=0.0490). Mean follow-up time of the study cohort was 6.58 years, and mean survival for patients undergoing AVR was 6.31 years. Conclusions Even after adjustment for clinical characteristics and patient age, AVR is associated with higher survival for patients with low LVEF and severe AR. Although treatment selection bias cannot be completely eliminated by this analysis, these results provide some evidence that surgery may be associated with prolonged survival in this high-risk patient group.

Endurance Exercise and the Right Ventricle Weak Link, Innocent Bystander, or Key Ingredient?

The cardiovascular response to high-intensity exercise has intrigued clinicians and scientists for more than a century. Since the initial reports of cardiac enlargement among Nordic skiers1 and rowers,2 a great deal has been learned about how the heart and vasculature remodel in response to endurance exercise. Through the efforts of many investigators and their athletic subjects, we now recognize the heart as an organ characterized by tremendous plasticity that permits chamber dilation and myocardial hypertrophy in response to the hemodynamic stressors inherent in endurance sporting activity. Our contemporary view of the endurance athlete’s heart includes attributes such as biventricular and biatrial dilation, mild to moderate ventricular hypertrophy, and normal to mildly reduced resting biventricular systolic function (as defined by ejection fractions).3 Functionally, this remodeling pattern facilitates stroke volume augmentation and thus increases cardiac output reserve during exercise. Yet, are these adaptations that facilitate successful endurance sport participation and lead to optimal athletic performance cost free? More specifically, do the short-term physiological benefits of exercise-induced cardiac remodeling come with long-term trade-offs that have undesirable clinical consequences? Article, see p 1927 These are not new questions. For as long as exercise-induced cardiac remodeling has been recognized, its clinical relevance with respect to health and longevity been questioned. In his sentinel 1899 article describing physiological adaptations in Harvard oarsmen, Thomas Darling wrote: “We have seen that a great increase in size and strength is demanded of this organ (the heart) and it may easily happen that it is called on for more work than it is able to do and that instead of establishing a compensatory hypertrophy it becomes diluted and weakened. A ‘broken-winded’ athlete is probably one with a dilated, flabby heart.”2 The principal question raised by Darling and many of his successors – Can the adaptive response …

Pulmonary Embolism Treatment

Pulmonary embolism (PE) is a common and highly morbid illness, with an estimated 530,000 cases of symptomatic PE in the USA annually. The prognosis of acute PE varies greatly depending on the clinical presentation. Submassive PE is defined as acute right ventricular (RV) dysfunction without systemic arterial hypotension. Massive PE is defined by the presence of hemodynamic shock from PE and is frequently life-threatening, with up to 58 % mortality in this population, making it the third most common cause of death in hospitalized patients.