Implementing Individually Tailored Prescription of Physical Activity in Routine Clinical Care: Protocol of the Physicians Implement Exercise = Medicine (PIE=M) Development and Implementation Project.

BACKGROUND: The prescription of physical activity (PA) in clinical care has been advocated worldwide. This "exercise is medicine" (E=M) concept can be used to prevent, manage, and cure various lifestyle-related chronic diseases. Due to several challenges, E=M is not yet routinely implemented in clinical care. OBJECTIVE: This paper describes the rationale and design of the Physicians Implement Exercise = Medicine (PIE=M) study, which aims to facilitate the implementation of E=M in hospital care. METHODS: PIE=M consists of 3 interrelated work packages. First, levels and determinants of PA in different patient and healthy populations will be investigated using existing cohort data. The current implementation status, facilitators, and barriers of E=M will also be investigated using a mixed-methods approach among clinicians of participating departments from 2 diverse university medical centers (both located in a city, but one serving an urban population and one serving a more rural population). Implementation strategies will be connected to these barriers and facilitators using a systematic implementation mapping approach. Second, a generic E=M tool will be developed that will provide tailored PA prescription and referral. Requirements for this tool will be investigated among clinicians and department managers. The tool will be developed using an iterative design process in which all stakeholders reflect on the design of the E=M tool. Third, we will pilot-implement the set of implementation strategies, including the E=M tool, to test its feasibility in routine care of clinicians in these 2 university medical centers. An extensive learning process evaluation will be performed among clinicians, department managers, lifestyle coaches, and patients using a mixed-methods design based on the RE-AIM framework. RESULTS: This project was approved and funded by the Dutch grant provider ZonMW in April 2018. The project started in September 2018 and continues until December 2020 (depending on the course of the COVID-19 crisis). All data from the first work package have been collected and analyzed and are expected to be published in 2021. Results of the second work package are described. The manuscript is expected to be published in 2021. The third work package is currently being conducted in clinical practice in 4 departments of 2 university medical hospitals among clinicians, lifestyle coaches, hospital managers, and patients. Results are expected to be published in 2021. CONCLUSIONS: The PIE=M project addresses the potential of providing patients with PA advice to prevent and manage chronic disease, improve recovery, and enable healthy ageing by developing E=M implementation strategies, including an E=M tool, in routine clinical care. The PIE=M project will result in a blueprint of implementation strategies, including an E=M screening and referral tool, which aims to improve E=M referral by clinicians to improve patients' health, while minimizing the burden on clinicians.

Targeted therapy of underlying conditions improves quality of life in patients with persistent atrial fibrillation: results of the RACE 3 study.

AIMS: Atrial fibrillation (AF) reduces quality of life (QoL). We aim to evaluate effects of targeted therapy of underlying conditions on QoL in patients with AF and heart failure (HF). METHODS AND RESULTS: The Routine versus Aggressive risk factor driven upstream rhythm Control for prevention of Early atrial fibrillation in heart failure (RACE 3) study randomized patients with early persistent AF and HF to targeted or conventional therapy. Both groups received guideline-driven treatment. The targeted group received four additional therapies: mineralocorticoid receptor antagonists; statins; angiotensin converting enzyme inhibitors and/or receptor blockers; and cardiac rehabilitation including physical activity, dietary restrictions, and counselling. Quality of life was analysed in 230 patients at baseline and 1 year with available Medical Outcomes Study Short-Form Health Survey (SF-36), University of Toronto AF Severity Scale (AFSS) questionnaires, and European Heart Rhythm Association (EHRA) class. Improvements in SF-36 subscales were larger in the targeted group for physical functioning (Δ12 ± 19 vs. Δ6 ± 22, P = 0.007), physical role limitations (Δ32 ± 41 vs. Δ17 ± 45, P = 0.018), and general health (Δ8 ± 16 vs. Δ0 ± 17, P < 0.001). Dyspnoea at rest improved more (Δ-0.8 ± 1.3 vs. Δ-0.4 ± 1.2, P = 0.018) and EHRA class was lower at 1-year follow-up in the targeted group. Patients with AF at 1 year, improvement in physical functioning (Δ9 ± 9 vs. Δ-3 ± 16, P = 0.001), general health (Δ7 ± 16 vs. Δ-7 ± 19, P = 0.004), and social functioning (Δ6 ± 23 vs. Δ-4 ± 16, P = 0.041) were larger in the targeted group. CONCLUSION: A strategy aiming to treat underlying conditions improved QoL more compared with conventional therapy in patients with early persistent AF and HF. Its benefit was even observed in patients in AF at 1 year. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00877643.

Targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent atrial fibrillation: results of the RACE 3 trial.

Aims: Atrial fibrillation (AF) is a progressive disease. Targeted therapy of underlying conditions refers to interventions aiming to modify risk factors in order to prevent AF. We hypothesised that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF. Methods and results: We randomized patients with early persistent AF and mild-to-moderate heart failure (HF) to targeted therapy of underlying conditions or conventional therapy. Both groups received causal treatment of AF and HF, and rhythm control therapy. In the intervention group, on top of that, four therapies were started: (i) mineralocorticoid receptor antagonists (MRAs), (ii) statins, (iii) angiotensin converting enzyme inhibitors and/or receptor blockers, and (iv) cardiac rehabilitation including physical activity, dietary restrictions, and counselling. The primary endpoint was sinus rhythm at 1 year during 7 days of Holter monitoring. Of 245 patients, 119 were randomized to targeted and 126 to conventional therapy. The intervention led to a contrast in MRA (101 [85%] vs. 5 [4%] patients, P < 0.001) and statin use (111 [93%] vs. 61 [48%], P < 0.001). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers were not different. Cardiac rehabilitation was completed in 109 (92%) patients. Underlying conditions were more successfully treated in the intervention group. At 1 year, sinus rhythm was present in 89 (75%) patients in the intervention vs. 79 (63%) in the conventional group (odds ratio 1.765, lower limit of 95% confidence interval 1.021, P = 0.042). Conclusions: RACE 3 confirms that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF. Trial Registration number: Clinicaltrials.gov NCT00877643.

[A new incentive for cardiac rehabilitation]. / Een nieuwe impuls voor hartrevalidatie.

Only a minority of patients receive cardiac rehabilitation after acute coronary syndrome, coronary bypass grafting or heart valve operation. A recent study published in the European Heart Journal, presents the results from approximately 36,000 patients who participated in a rehabilitation program. It showed a 35% reduction in mortality during 4-year follow-up. Modern cardiac rehabilitation does not only focus on physical training but also includes interactive education, relaxation therapy, coping and self-management. Patients are also encouraged to participate in structural physical activity, which is incorporated into their daily life after the rehabilitation program. From other studies we know that not only is mortality reduced but also quality of life is improved as a result of cardiac rehabilitation. We both strongly recommend and encourage our colleagues to refer their cardiac patients to a multidisciplinary cardiac rehabilitation program.

Daily physical activity in stable heart failure patients.

BACKGROUND: Physical activity is the only nonpharmacological therapy that is proven to be effective in heart failure (HF) patients in reducing morbidity. To date, little is known about the levels of daily physical activity in HF patients and about related factors. OBJECTIVE: The objectives of this study were to (a) describe performance-based daily physical activity in HF patients, (b) compare it with physical activity guidelines, and (c) identify related factors of daily physical activity. METHODS: The daily physical activity of 68 HF patients was measured using an accelerometer (SenseWear) for 48 hours. Psychological characteristics (self-efficacy, motivation, and depression) were measured using questionnaires. To have an indication how to interpret daily physical activity levels of the study sample, time spent on moderate- to vigorous-intensity physical activities was compared with the 30-minute activity guideline. Steps per day was compared with the criteria for healthy adults, in the absence of HF-specific criteria. Linear regression analyses were used to identify related factors of daily physical activity. RESULTS: Forty-four percent were active for less than 30 min/d, whereas 56% were active for more than 30 min/d. Fifty percent took fewer than 5000 steps per day, 35% took 5000 to 10 000 steps per day, and 15% took more than 10 000 steps per day. Linear regression models showed that New York Heart Association classification and self-efficacy were the most important factors explaining variance in daily physical activity. CONCLUSIONS: The variance in daily physical activity in HF patients is considerable. Approximately half of the patients had a sedentary lifestyle. Higher New York Heart Association classification and lower self-efficacy are associated with less daily physical activity. These findings contribute to the understanding of daily physical activity behavior of HF patients and can help healthcare providers to promote daily physical activity in sedentary HF patients.

The clinical course of hepatitis E virus infection in patients of a tertiary Dutch hospital over a 5-year period.

BACKGROUND: Hepatitis E virus (HEV) has long been known as a major cause of acute hepatitis in developing countries with occasional travel-related cases in developed countries, most of them belonging to genotype 1. Currently, genotype 3 HEV is recognized as an emerging public health issue in developed countries and can cause a chronic hepatitis in immunocompromised patients. OBJECTIVES: The aim of this study was to get an overview of the clinical course of HEV infection, from July 2007 to December 2012, and further characterize HEV in patients of the University Medical Center Groningen (UMCG) over a 5-year time period. METHODS: Since the second half of 2007, patients in the UMCG with unexplained hepatitis were screened for HEV and clinical data were collected. HEV was characterized by sequencing of the ORF1 and ORF2 regions. RESULTS: In total, 34 patients of the 1129 tested patients showed HEV viremia. The majority of the infected patients were immunocompromised; 18 were solid organ transplant (SOT) patients and 9 were patients immunocompromised for other reasons. Seven patients diagnosed with HEV were immunocompetent. Viral genotyping revealed genotype 3 isolates, mostly genotype 3c. CONCLUSION: Non-travel related HEV hepatitis is an important diagnosis. In immunocompromised patients HEV infection often has major clinical impact, necessitating medical intervention including antiviral treatment. In immunocompetent patients, the detection could expand our understanding about the route of transmission and the relation with the zoonotic origin. Therefore, besides an increasing awareness for HEV among clinicians and medical microbiologists, diagnostics should be routinely incorporated into standard patients care.

Mitral valve repair and redo repair for mitral regurgitation in a heart transplant recipient.

A 37-year-old man with end-stage idiopathic dilated cardiomyopathy underwent an orthotopic heart transplant followed by a reoperation with mitral annuloplasty for severe mitral regurgitation. Shortly thereafter, he developed severe tricuspid regurgitation and severe recurrent mitral regurgitation due to annuloplasty ring dehiscence. The dehisced annuloplasty ring was refixated, followed by tricuspid annuloplasty through a right anterolateral thoracotomy. After four years of follow-up, there are no signs of recurrent mitral or tricupid regurgitation and the patient remains in NYHA class II. Pushing the envelope on conventional surgical procedures in marginal donor hearts (both before and after transplantation) may not only improve the patient's functional status and reduce the need for retransplantation, but it may ultimately alleviate the chronic shortage of donor hearts.

Two donor-related infections in a heart transplant recipient: one common, the other a tropical surprise.

BACKGROUND: Infection is the most frequent complication after heart transplantation (HTx). In this report and brief literature review we present a recipient who some 6 weeks post-HTx had two donor-related infections: a "common" primary cytomegalovirus (CMV) infection and, simultaneously, a highly unusual donor-related Strongyloides stercoralis infection. METHODS: The parasite was discovered by chance in a skin biopsy. CMV was treated with ganciclovir and the strongyloidiasis was cured with two courses of anti-helminthic therapy--initially with ivermectine and albendazol and, in response to eosinophilia, with ivermectine monotherapy. The patient's recovery was further complicated by two successive rejection episodes, a relapse of the CMV syndrome and a novel influenza A/H1N1 infection. These episodes were treated with steroids, ganciclovir and oseltamivir, respectively. RESULTS: It took almost 9 months before a permanent IgG anti-CMV response was seen. At 13 months post-HTx, coronary angiography showed only slight vessel wall abnormalities. At present, the patient is back at home and in good condition. CONCLUSION: Until now, only 4 recipient-derived strongyloidiasis cases have been described in post-HTx patients, all diagnosed by autopsies. This is the first report of a donor-related Strongyloides infection in a patient after HTx.

[Clinical cardiac rehabilitation]. / Klinische hartrevalidatie.

Outpatient cardiac rehabilitation (CR) is offered in at least 100 hospitals in the Netherlands. The majority of cardiac patients are well-served with physical training and education. Some patients with complex cardiac pathology and other problems, including health problems, may however benefit from multidisciplinary in-hospital CR. We present three cardiac patients. The first patient, a 58-year-old man, had coronary and pulmonary disease, suboptimally treated diabetes and psychological problems. He participated in in-hospital CR for 7 weeks, which led to an improved physical and emotional condition. The second patient was 80 years old and did not recover properly following an aortic valve replacement. With in-hospital CR she acquired new skills for mastering the activities of daily life. The third patient we described, a 57-year-old man, suffered from ischaemic heart failure and had had recurrent implantable cardiac defibrillator (ICD) shocks. He was referred for cardiac transplantation but 7 weeks of in-hospital CR resulted in an improved exercise tolerance, significant weight loss and an adequate level of coping with his disease. In-hospital CR is a niche service, but may provide relief for some cardiac patients.

[Experiences of combined heart-lung transplantations in the University Medical Center Groningen]. / Ervaringen met gecombineerde hart-longtransplantatie in het Universitair Medisch Centrum Groningen.

OBJECTIVE: Reporting the results of combined heart-lung transplantation in the University Medical Center Groningen (UMCG), the Netherlands. DESIGN: Retrospective study. METHOD: Data were retrieved of patients who underwent a combined heart-lung transplantation in the UMCG between December 1996 and December 2007. Demographic, clinical and other relevant characteristics were recorded, as well as post-transplantation morbidity and mortality. RESULTS: The study group consisted of 14 patients (3 men and 11 women) with a mean age of 41 years. Indications for heart-lung transplantation were: congenital heart disease complicated by pulmonary hypertension (6 patients), idiopathic pulmonary hypertension with severe right ventricle failure (4 patients), lung fibrosis with severe right ventricle failure (1 patient), cystic fibrosis with systolic left ventricle failure (1 patient), pulmonary hypertension after thoracic radiation and chemotherapy (1 patient) and re-transplantation after lung-transplant failure (1 patient). The mean waiting time prior to operation was approximately 1.5 years. 9 of the 14 patients (64%) underwent such a marked clinical deterioration during the waiting period that they were given a 'very high urgency status' for transplantation. Almost half of patients became dependent on supplementary intravenous inotropics during the waiting period. At the end of the study 6 of the 14 patients (43%) were alive, with a mean survival period of 58 months (range: 6-132). Infection was the cause of death in 4 of the 8 patients. Of the 8 deceased patients, 4 were underweight preoperatively (BMI < 18.5 kg/m2) and were cachectic. This was the case in only 1 of the 6 surviving patients. CONCLUSION: A combined heart-lung transplantation is a rare operation in the Netherlands. The waiting time in this study was long and the post-transplantation mortality was high. Underweight (cachexia), a sign of a poor clinical condition, appears to be associated with mortality.

Importance of heart rate during exercise for response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60-70% of patients. OBJECTIVES: To study exercise-related factors predicting response to CRT. METHODS: We retrospectively examined consecutive patients in whom a CRT device was implanted. All underwent cardiopulmonary exercise testing prior to implantation and after 6 months. The occurrence of chronotropic incompetence and heart rates exceeding the upper rate of the device, thereby compromising biventricular stimulation, was studied. Response was defined as a decrease in LVESV of 10% or more after 6 months. RESULTS: We included 144 patients. After 6 months 86 (60%) patients were responders. Peak VO2 significantly increased in responders. Chronotropic incompetence was more frequently seen in nonresponders (21 [36%] vs 9 [10%], P = 0.03), mostly in patients in SR. At moderate exercise, defined as 25% of the maximal exercise tolerance, that is, comparable to daily life exercise, nonresponders more frequently went above the upper rate of the device (13 [22%] vs 2 [3%], P < 0.0001), most of whom were patients in permanent AF. Multivariate analysis revealed heart rates not exceeding the upper rate of the device during moderate exercise (OR 15.8 [3.3-76.5], P = 0.001) and nonischemic cardiomyopathy (OR 2.4 [1.0-5.7], P = 0.04) as predictive for response. CONCLUSIONS: Heart rate exceeding the upper rate during moderate exercise is an independent predictor for nonresponse to CRT in patients with AF, whereas chronotropic incompetence is a predictor for patients in SR.

A randomised controlled trial of cardiac rehabilitation after revascularisation.

BACKGROUND: It is unclear if psycho-education on top of physical training is of additional value regarding quality of life in revascularised patients. DESIGN: Prospective randomised study comparing two types of cardiac rehabilitation: exercise based versus a more comprehensive approach including psychological therapy. METHODS: One hundred and thirty-seven male patients who underwent an uncomplicated coronary revascularisation procedure and who were mentally in a good condition, were randomised to one of two types of cardiac rehabilitation: physical training plus information about their disease ('Fit' program) during 6 weeks or comprehensive cardiac rehabilitation which, on top of the Fit-program, included weekly psycho-education sessions and relaxation therapy ('Fit-Plus' program) for 8 weeks. One hundred and four patients were analysed. Quality of life was measured by the 'Leiden Quality of Life questionnaire' and by the RAND-36 (quality of life) questionnaire. RESULTS: Quality of life improved in both treatment groups in the course of time up to 9 months after cardiac rehabilitation and there was no difference between the two types of cardiac rehabilitation. Exercise capacity improved likewise, blood lipid profile was unaffected and energy intake decreased in each treatment group but, again, there were no inter-group differences. CONCLUSION: After an uncomplicated revascularisation procedure, physical training plus information results in a comparable outcome on quality of life when compared to a more comprehensive program including additional psycho-education and relaxation therapy.

Serial right ventricular endomyocardial biopsy in rapid-onset severe heart failure due to giant cell myocarditis.

Giant cell myocarditis (GCM) is a serious condition that warrants immediate diagnosis and treatment. It often presents as rapidly progressive heart failure and/or malignant ventricular arrhythmias. Here, we describe a 34-year-old patient with myasthenia gravis who presented with GCM 2 weeks after resection of a thymoma. A cardiac biopsy confirming the diagnosis was done within 3 days after admission. After institution of an aggressive immunosuppressive drug regimen, implantation of an implantable cardioverter defibrillator, and intensive cardiac rehabilitation, the patient recovered dramatically. In control biopsies after 4 weeks and 6 months, no more giant cells were found. We conclude that, in the case of nonischemic acute heart failure in young patients, a biopsy should be performed as soon as possible to prevent an unfavourable outcome of this often fatal disease.

Fear of exercise and health-related quality of life in patients with an implantable cardioverter defibrillator.

Several studies have reported improved survival rates thanks to the use of an implantable cardioverter defibrillator (ICD) in the treatment of patients with life-threatening arrhythmia. However, the effects of the ICD on health-related quality of life (HR-QoL) of these patients are not clear. The aim of this study is to describe HR-QoL and fear of exercise in ICD patients. Eighty-nine ICD patients from the University Hospital in Groningen, the Netherlands, participated in this study. HR-QoL was measured using the Rand-36 and the Quality of Life After Myocardial Infarction Dutch language version questionnaires. Fear of exercise was measured using the Tampa Scale for Kinesiophobia, Dutch version and the Fear Avoidance Beliefs Questionnaire, Dutch version. Association between outcome variables was analysed by linear regression analyses. Study results show that the HR-QoL of patients with ICDs in our study population is significantly worse than that of normal healthy people. Furthermore, fear of exercise is negatively associated with HR-QoL corrected for sex, age and number of years living with an ICD. After implantation of the ICD, patients with a clear fear of exercise should be identified and interventions should be considered in order to increase their HR-QoL.