Musclin is an activity-stimulated myokine that enhances physical endurance.

Exercise remains the most effective way to promote physical and metabolic wellbeing, but molecular mechanisms underlying exercise tolerance and its plasticity are only partially understood. In this study we identify musclin-a peptide with high homology to natriuretic peptides (NP)-as an exercise-responsive myokine that acts to enhance exercise capacity in mice. We use human primary myoblast culture and in vivo murine models to establish that the activity-related production of musclin is driven by Ca(2+)-dependent activation of Akt1 and the release of musclin-encoding gene (Ostn) transcription from forkhead box O1 transcription factor inhibition. Disruption of Ostn and elimination of musclin secretion in mice results in reduced exercise tolerance that can be rescued by treatment with recombinant musclin. Reduced exercise capacity in mice with disrupted musclin signaling is associated with a trend toward lower levels of plasma atrial NP (ANP) and significantly smaller levels of cyclic guanosine monophosphate (cGMP) and peroxisome proliferator-activated receptor gamma coactivator 1-α in skeletal muscles after exposure to exercise. Furthermore, in agreement with the established musclin ability to interact with NP clearance receptors, but not with NP guanyl cyclase-coupled signaling receptors, we demonstrate that musclin enhances cGMP production in cultured myoblasts only when applied together with ANP. Elimination of the activity-related musclin-dependent boost of ANP/cGMP signaling results in significantly lower maximum aerobic capacity, mitochondrial protein content, respiratory complex protein expression, and succinate dehydrogenase activity in skeletal muscles. Together, these data indicate that musclin enhances physical endurance by promoting mitochondrial biogenesis.

Cardiovascular Complications of Coronavirus Disease-2019.

Cardiovascular complications associated with the severe acute respiratory syndrome coronavirus 2 infection are common and lead to high mortality in the acute phase and high morbidity in the chronic phase impacting an individual's quality of life and health outcomes. Patients afflicted with coronavirus disease-2019 (COVID-19) infection display an increased risk for myocarditis, dysrhythmia, pericarditis, ischemic heart disease, heart failure, and thromboembolism. Although cardiovascular complications are reported across all patients with COVID-19, hospitalized patients with severe infection are most vulnerable. The underline pathobiology remains poorly defined albeit complex. Following current guidelines in decision-making for evaluation and management in addition to the beginning or returning exercise is recommended.

Clinical Significance of Biological Age in Patients Undergoing Percutaneous Coronary Intervention.

OBJECTIVE: To test whether biological age calculated using deficits, functional impairments, or their combination will provide improved estimation of long-term mortality among older adults undergoing percutaneous coronary intervention. PATIENTS AND METHODS: Cardiovascular deficits, noncardiovascular deficits, and functional impairments were prospectively studied in 535 patients aged 55 years or older from August 1, 2014, to March 31, 2018. Models for biological age included deficits (acquired, increase with age, associated with worse prognosis, did not saturate early), functional impairments (subjective-help with daily activities, difficulty with sensory input, continence, weight, balance, mobility; or objective-timed up and go, functional reach), or their combination. RESULTS: The mean ± SD age of the study patients was 72.1±9.5 years. For every 5-year increase in chronological age, the mean number of cardiovascular deficits increased from 2.36 among patients younger than 70 years to 3.44 in nonagenarians. The mean number of functional impairments increased from 2.15 for those younger than 70 years to 6.74 for nonagenarians. During a median follow-up of 2.05 years, 99 patients died. Significant improvement in the Harrell concordance index (C index) for prediction of long-term all-cause mortality was noted with biological age calculated from deficits and impairments compared with chronological age (0.77 vs 0.65; P<.001) and when estimating biological age via functional impairments alone vs chronological age (0.75 vs 0.65; P<.001) but not via deficits alone (0.71 vs 0.65; P=.08). Biological age estimates from subjective functional impairments captured most of the prognostic information related to all-cause and noncardiac mortality, whereas deficit-based estimation favored cardiovascular mortality. CONCLUSION: The derivation of biological age from deficits and functional impairments provides a major improvement in the estimation of survival as estimated by chronological age.

Impact of Musculoskeletal Limitations on Cardiac Rehabilitation Participation.

Background: To help clarify a potential barrier to cardiac rehabilitation (CR) participation we sought to examine the association between musculoskeletal limitations (MSLs) and CR enrollment and participation. Methods: Consecutive CR eligible individuals hospitalized for a cardiac event (myocardial infarction, percutaneous coronary intervention, and/or coronary artery bypass graft) between the months of November 2007 and May 2008, were asked to complete a mailed survey within 2 weeks after hospital discharge, assessing demographic factors, Patient Health Questionnaire (PHQ-9), participation in CR and MSLs through a validated MSLs screening tool. CR enrollment rates were compared between patients with and without MSLs. Results: Three hundred and twenty-one (37%) of patients contacted responded to our survey, including 228 males (71%), with a mean age 68 ± 10.8 years, of whom 98% were Caucasian. Eighty-two percent of responders reported a musculoskeletal disorder at the time of hospital discharge. Arthritis was the most frequent diagnosis (45%). Muscle or joint pain sufficient to limit the ability to do moderate exercise was reported in 52% of the respondents. Problems with balance affected 37%, of whom 45% reported a fall within the previous year. No significant difference in CR enrollment was observed in respondents with and without MSLs [OR = 0.98, 95% CI (0.88-1.09), p = 0.750]. Similar results were found when severity and number of MSLs were taken into account. However, we found that when compared to those without MSLs, the presence of MSLs was associated with lower CR participation (OR = 0.80, 95%, CI: 0.65-0.97, p = 0.0252). Conclusion: Despite a high prevalence of MSLs among CR-eligible patients, we found no association between MSLs and CR enrollment. However, patients with MSLs attended significantly fewer CR sessions as compared to patients without them. CR programs should consider providing additional support and interventions to patients with MSLs in order to optimize their adherence to prescribed CR sessions.

The Telemedicine Musculoskeletal Examination.

Telemedicine uses modern telecommunication technology to exchange medical information and provide clinical care to individuals at a distance. Initially intended to improve health care for patients in remote settings, telemedicine now has a broad clinical scope with the general purpose of providing convenient, safe, and time- and cost-efficient care. The coronavirus disease 2019 pandemic has created marked nationwide changes in health care access and delivery. Elective appointments and procedures have been canceled or delayed, and multiple states still have some degree of shelter-in-place orders. Many institutions are now relying more heavily on telehealth services to continue to provide medical care to individuals while also preserving the safety of health care professionals and patients. Telemedicine can also help reduce the surge in health care needs and visits as restrictions are lifted. In recent weeks, there has been a significant amount of information and advice on how to best approach telemedicine visits. Given the frequent presentation of individuals with musculoskeletal complaints to the medical practitioner, it is important to have a framework for the virtual musculoskeletal physical examination. This will be of importance as telemedicine continues to evolve, even after coronavirus disease 2019 restrictions are lifted. This article will provide the medical practitioner performing a virtual musculoskeletal examination with a specific set of guidelines, both written and visual, to enhance the information obtained when evaluating the shoulder, hip, knee, ankle, and cervical and lumbar spine. In addition to photographs, accompanying videos are included to facilitate and demonstrate specific physical examination techniques that the patient can self-perform.

Severity of Depressive Symptoms Pre- and Postcardiac Rehabilitation: A COMPARISON AMONG PATIENTS IN BRAZIL, CANADA, COLOMBIA, THE UNITED STATES, AND VENEZUELA.

PURPOSE: Depression is 3 times more prevalent in the cardiac than the general population in high-income countries and is particularly high in middle-income countries. Comorbid depression is associated with twice the mortality after a cardiovascular event. The objectives of this study were to describe and compare depressive symptoms pre- and postcardiac rehabilitation (CR) among patients in high-income countries and middle-income countries in the Americas. METHODS: The study design was prospective and observational. A convenience sample of CR participants completed the Patient Health Questionnaire-9 (PHQ-9) at CR intake and again at program discharge. Clinical data were extracted from medical charts. RESULTS: There were 779 participants: 45 Brazilian (5.8% of sample), 214 Canadian (27.5%), 126 Colombian (16.2%), 309 American (39.7%), and 85 Venezuelan (10.9%). Pre-CR depressive symptoms significantly differed between countries (P < .05), with Colombian participants reporting higher scores than Canadians and Venezuelans. Total PHQ-9 scores significantly decreased during CR in Colombia (mean change =-2.33; P < .001), the United States (mean change =-1.12; P < .001), and Venezuela (mean change =-2.14; P < .001), but not in Brazil (where less psychosocial intervention was offered) or Canada (where pre-CR scores were low). Among the 102 (13.1%) participants with scores in the elevated range pre-CR, the mean change in PHQ-9 scores was -6.57 ± 1.09 and 40 (39.2%) participants no longer had elevated symptoms postprogram. CONCLUSIONS: Depressive symptoms are variable among patients with CR in South and North American countries. CR programs incorporating psychosocial components can reduce these symptoms.

Cardiac Rehabilitation for Women: A Systematic Review of Barriers and Solutions.

Cardiac rehabilitation (CR) services improve various clinical outcomes in patients with cardiovascular disease, but such services are underutilized, particularly in women. The aim of this study was to identify evidence-based barriers and solutions for CR participation in women. A literature search was carried out using PubMed, EMBASE, Cochrane, OVID/Medline, and CINAHL to identify studies that have assessed barriers and/or solutions to CR participation. Titles and abstracts were screened, and then the full-text of articles that met study criteria were reviewed. We identified 24 studies that studied barriers to CR participation in women and 31 studies that assessed the impact of various interventions to improve CR referral, enrollment, and/or completion of CR in women. Patient-level barriers included lower education level, multiple comorbid conditions, non-English native language, lack of social support, and high burden of family responsibilities. We found support for the use of automatic referral and assisted enrollment to improve CR participation. A small number of studies suggest that incentive-based strategies, as well as home-based programs, may contribute to improving CR attendance and completion rates. A systematic approach to CR referral, including automatic CR referral, may help overcome barriers to CR referral in women and should be implemented in clinical practice. However, more studies are needed to help identify the best methods to improve CR attendance and completion of CR rates in women.

Regenerative Therapy Prevents Heart Failure Progression in Dyssynchronous Nonischemic Narrow QRS Cardiomyopathy.

BACKGROUND: Cardiac resynchronization therapy using bi-ventricular pacing is proven effective in the management of heart failure (HF) with a wide QRS-complex. In the absence of QRS prolongation, however, device-based resynchronization is reported unsuitable. As an alternative, the present study tests a regenerative cell-based approach in the setting of narrow QRS-complex HF. METHODS AND RESULTS: Progressive cardiac dyssynchrony was provoked in a chronic transgenic model of stress-triggered dilated cardiomyopathy. In contrast to rampant end-stage disease afflicting untreated cohorts, stem cell intervention early in disease, characterized by mechanical dyssynchrony and a narrow QRS-complex, aborted progressive dyssynchronous HF and prevented QRS widening. Stem cell-treated hearts acquired coordinated ventricular contraction and relaxation supporting systolic and diastolic performance. Rescue of contractile dynamics was underpinned by a halted left ventricular dilatation, limited hypertrophy, and reduced fibrosis. Reverse remodeling reflected a restored cardiomyopathic proteome, enforced at systems level through correction of the pathological molecular landscape and nullified adverse cardiac outcomes. Cell therapy of a dyssynchrony-prone cardiomyopathic cohort translated prospectively into improved exercise capacity and prolonged survivorship. CONCLUSIONS: In narrow QRS HF, a regenerative approach demonstrated functional and structural benefit, introducing the prospect of device-autonomous resynchronization therapy for refractory disease.

Singing paraplegia: a distinctive manifestation of a spinal dural arteriovenous fistula.

The unique case of a baritone with a spinal dural arteriovenous fistula (SDAVF) causing recurrent, acute paraplegia during singing is described. This case underscores the presence of impaired venous drainage in these lesions and the high level of clinical suspicion required for their diagnosis in patients with any myelopathy.

Ethnocultural diversity in cardiac rehabilitation.

Cardiovascular disease is the leading cause of death globally. Despite a greater burden of disease, ethnocultural minorities in both the United States and Canada are significantly less likely to access cardiac rehabilitation (CR). Without equitable access to CR, these patients may be more likely to experience recurrent cardiac events and unnecessarily premature death. In this article, the current state of ethnocultural diversity in CR patients and unique barriers that ethnocultural minority patients face are reviewed. Strategies for CR program delivery and diversity of CR program staff are considered. Guidance on ethnocultural considerations in American and Canadian associations of CR is also reviewed. Lower rates of access to CR are seen among ethnocultural minorities in both American and Canadian CR programs. Only 2 studies evaluating ethnoculturally tailored CR could be identified in the literature. American CR staff are predominantly white (∼96%), whereas ethnocultural data are not collected from Canadian CR professionals. American guidelines emphasize the importance of ethnocultural competency. Meanwhile, Canadian guidelines underscore the low use of CR services among ethnocultural minorities, and support ethnoculturally informed CR delivery. The American and Canadian populations are rapidly diversifying, yet the CR workforce is not, and ethnocultural minorities continue to be underrepresented in our programs. Although recent CR guidelines have made some preliminary recommendations to overcome these discrepancies, more focused efforts are needed. Thirteen points of action are proposed for the CR community with the goal of promoting the development and delivery of more ethnoculturally sensitive CR services.

Regenerative principles enrich cardiac rehabilitation practice.

Cardiovascular morbidity imposes a high degree of disability and mortality, with limited therapeutic options available in end-stage disease. Integral to standard of care, cardiac rehabilitation aims on improving quality-of-life and prolonging survival. The recent advent of regenerative technologies paves the way for a transformative era in rehabilitation medicine whereby, beyond controlling risk factors and disease progression, the prospect of curative solutions is increasingly tangible. To date, the spectrum of clinical experience in cardiac regenerative medicine relies on stem cell-based therapies delivered to the diseased myocardium either acutely/subacutely, after a coronary event, or in the setting of chronic heart failure. Application of autologous/allogeneic stem cell platforms has established safety and feasibility, with encouraging signals of efficacy. Newer protocols aim to purify cell populations in an attempt to eliminate nonregenerative and enrich for regenerative cell types before use. Most advanced technologies have been developed to isolate resident cell populations directly from the heart or, alternatively, condition cells from noncardiac sources to attain a disease-targeted lineage-specified phenotype for optimized outcome. Because a multiplicity of cell-based technologies has undergone phase I/II evaluation, pivotal trials are currently underway in larger patient populations. Translation of regenerative principles into clinical practice will increasingly involve rehabilitation providers across the continuum of patient care. Regenerative rehabilitation is thus an emerging multidisciplinary field, full of opportunities and ready to be explored.

Inpatient rehabilitation outcomes for patients receiving left ventricular assist device.

OBJECTIVE: The aim of this study was to evaluate outcomes of patients participating in inpatient rehabilitation program after left ventricular assist device (LVAD) implantation. DESIGN: Medical records of 94 patients who received LVADs between January 1, 2008, and June 30, 2010, at the Mayo Clinic in Rochester, MN, were retrospectively reviewed for demographic data, and inpatient rehabilitation functional outcomes were measured by the Functional Independence Measure scale. RESULTS: After successful implantation of LVAD, the patients were either discharged directly home from acute care (44%) or admitted to inpatient rehabilitation (56%). The patients admitted to inpatient rehabilitation were older than those discharged home. They were also more medically complex and more likely to have the LVAD placed as destination therapy. At discharge, significant improvement occurred in 17 of the 18 activities evaluated by the Functional Independence Measure scale. The mean total Functional Independence Measure scale score at admission was 77.1 compared with a score of 95.2 at discharge (P < 0.0001). CONCLUSIONS: Approximately half of the patients who received LVAD therapy were admitted in the inpatient rehabilitation. After the implantation of LVAD and inpatient rehabilitation, significant functional improvements were observed. Further studies addressing the role of inpatient rehabilitation for LVAD patients are warranted.

Improving cardiac rehabilitation attendance and completion through quality improvement activities and a motivational program.

PURPOSE: Recent studies have demonstrated that patients who attend more cardiac rehabilitation (CR) sessions have lower subsequent mortality rates than those who attend fewer sessions. METHODS: We analyzed the impact of several phased-in policy and process changes implemented to increase patient participation in CR. In March 2010, our CR program changed from a policy of individualizing the recommended number of CR sessions per patient to a policy that recommended all 36 CR sessions. In October 2010, we introduced a 7-minute video describing the benefits of CR. In August 2011, we introduced a motivational program that rewarded patients after every sixth CR session. The number of CR sessions attended was determined through review of billing records. Enrollment and completion were defined as attending ≥1 session and ≥30 sessions, respectively. RESULTS: We identified 1103 patients sequentially enrolled in CR between May 2009 and January 2012. Overall, the median number of sessions per patient improved from 12 to 20 (P < .001). Completion rate improved from 14% to 39% (P < .001). The motivational program increased attendance by a median of 3 sessions per patient (P = .04), but this effect was limited to local CR participants. Financial analysis suggested that for every $100 spent on motivational rewards, patients attended an additional 6.6 (95% CI, -1 to 14) sessions of CR. CONCLUSIONS: Quality improvement activities significantly increased CR participation. Wide implementation of such programs may favorably impact patient participation in CR and potentially decrease the rate of subsequent cardiac events.

Mechanical dyssynchrony precedes QRS widening in ATP-sensitive K⁺ channel-deficient dilated cardiomyopathy.

BACKGROUND: Contractile discordance exacerbates cardiac dysfunction, aggravating heart failure outcome. Dissecting the genesis of mechanical dyssynchrony would enable an early diagnosis before advanced disease. METHODS AND RESULTS: High-resolution speckle-tracking echocardiography was applied in a knockout murine surrogate of adult-onset human cardiomyopathy caused by mutations in cardioprotective ATP-sensitive K(+) (K(ATP)) channels. Preceding the established criteria of cardiac dyssynchrony, multiparametric speckle-based strain resolved nascent erosion of dysfunctional regions within cardiomyopathic ventricles of the K(ATP) channel-null mutant exposed to hemodynamic stress. Not observed in wild-type counterparts, intraventricular disparity in wall motion, validated by the degree, direction, and delay of myocardial speckle patterns, unmasked the disease substrate from asymptomatic to overt heart failure. Mechanical dyssynchrony preceded widening of the QRS complex and exercise intolerance and progressed into global myocardial discoordination and decompensated cardiac pump function, precipitating a low output syndrome. CONCLUSIONS: The present study, with the use of high-resolution imaging, prospectively resolved the origin and extent of intraventricular motion disparity in a K(ATP) channel-knockout model of dilated cardiomyopathy. Mechanical dyssynchrony established as an early marker of cardiomyopathic disease offers novel insight into the pathodynamics of dyssynchronous heart failure.

Exercise in cardiovascular diseases.

Analysis of extensive data has shown that exercise training provides significant impact on prevention and modification of cardiovascular diseases and mortality. In general, exercise recommendations for patients with cardiovascular diseases are based on individual aerobic capacity and comorbidities. Patients with acute syndromes benefit from participating in a cardiac rehabilitation program, whereas patients with chronic syndromes benefit from a life-long home-based program. In general, exercise prescription should involve aerobic activities in combination with resistance, flexibility, and balance exercises. This review will discuss an exercise prescription for patients with coronary artery disease, heart failure, and after heart transplantation. Detailed precautions for particular groups of patients will be discussed.

Prevalence of musculoskeletal and balance disorders in patients enrolled in phase II cardiac rehabilitation.

PURPOSE: To determine the prevalence of musculoskeletal, neurological, and balance problems in patients enrolled in early outpatient (phase II) cardiac rehabilitation. METHODS: Data were assessed retrospectively for 284 consecutive patients who attended the phase II Mayo Clinic Cardiac Rehabilitation program from April 2005 to August 2006. All participants completed a questionnaire that identified the presence of musculoskeletal pain, history of falls, joint replacements, osteoporosis, neurological disorders, and difficulties in performing activities of daily living. Balance assessment was evaluated using the single leg stance and the tandem gait tests. RESULTS: Of the total study population (mean age, 62.1 +/- 12.3 years), 25% reported musculoskeletal pain. A significantly higher prevalence of pain was noted in women than men (37% vs 20%, P = .004) and in those > 65 years than those < or = 65 years (35% vs 17%, P = .001). Back (29%), knee (17%), and hip (8%) pain were the most common symptoms, in order of decreasing frequency. Pain was worse with any activity in 32% of participants while 16% of participants had worsening at night. An abnormality in balance was present in 58% of the study participants and was significantly more common in women (71%) and those > 65 years (83%). Falls or gait instability or both were reported by 11% of participants. CONCLUSION: Musculoskeletal and balance limitations are common in persons enrolled in early outpatient cardiac rehabilitation, particularly in women and patients > 65 years. Cardiac rehabilitation programs should screen patients for musculoskeletal limitations and incorporate adaptations for treatment strategies of such patients.