The prevalence and impact of sarcopenia in older cardiac patients undergoing inpatient cardiac rehabilitation - results from a prospective, observational cohort pre-study.

BACKGROUND: The prevalence of sarcopenia and its impact in older patients undergoing inpatient cardiac rehabilitation (iCR) after cardiac procedure has been insufficiently studied. The main aim of this study was to evaluate the prevalence of sarcopenia and quantify the functional capacity of older sarcopenic and non-sarcopenic patients participating in iCR. METHODS: Prospective, observational cohort study within the framework of the ongoing multicenter prehabilitation study "PRECOVERY". A sample of 122 patients ≥75 years undergoing iCR after cardiac procedure were recruited in four German iCR facilities and followed up 3 months later by telephone. At iCR (baseline), the Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls (SARC-F) questionnaire was used to identify sarcopenic patients. In addition, Katz-Index, Clinical Frailty Scale (CFS), handgrip strength (HGS), Short Physical Performance Battery (SPPB) and 6-minute walk distance (6MWD) measured functional capacity and frailty at baseline. Outcomes were prevalence of sarcopenia and the correlation of sarcopenia to functional capacity and frailty at baseline as well as the SARC-F score at follow-up. The Wilcoxon test was applied for pre-post-test analysis. Correlation between sarcopenia and 6MWD, SPPB score and HGS was tested with the eta coefficient with one-way ANOVA. RESULTS: Complete assessments were collected from 101 patients (79.9 ± 4.0 years; 63% male). At baseline, the mean SARC-F score was 2.7 ± 2.1; 35% with sarcopenia. Other baseline results were Katz-Index 5.7 ± 0.9, CFS 3.2 ± 1.4, HGS 24.9 ± 9.9 kg, SPPB score 7.5 ± 3.3 and 6MWD 288.8 ± 136.5 m. Compared to baseline, fewer patients were sarcopenic (23% versus 35%) at follow-up. In the subgroup of sarcopenic patients at baseline (n = 35), pre-post comparison resulted in a significant SARC-F improvement (p = 0.017). There was a significant correlation between sarcopenia measured by SARC-F and poor results in the assessments of functional capacity (p < 0.001; r > 0.546). CONCLUSIONS: The prevalence of sarcopenia in older patients at iCR after cardiac procedure is high (35%) and remains high at follow-up (23%). Sarcopenia screening is important since the diagnosis of sarcopenia in these patients correlates significantly with poor functional capacity. The results indicate that these patients may benefit from prehabilitation aimed at improving perioperative outcomes, increasing functional capacity and mitigating adverse effects. TRIAL REGISTRATION: German Clinical Trials Register (DRKS; http://www.drks.de ; DRKS00032256). Retrospectively registered on 13 July 2023.

Prehabilitation in older patients prior to elective cardiac procedures (PRECOVERY): study protocol of a multicenter randomized controlled trial.

BACKGROUND: Previous studies have demonstrated the efficacy of rehabilitation after a cardiovascular procedure. Especially older and multimorbid patients benefit from rehabilitation after a cardiac procedure. Prehabilitation prior to cardiac procedures may also have positive effects on patients' pre- and postoperative outcomes. Results of a current meta-analysis show that prehabilitation prior to cardiac procedures can improve perioperative outcomes and alleviate adverse effects. Germany currently lacks a structured cardiac prehabilitation program for older patients, which is coordinated across healthcare sectors. METHODS: In a randomized, controlled, two-arm parallel group, assessor-blinded multicenter intervention trial (PRECOVERY), we will randomize 422 patients aged 75 years or older scheduled for an elective cardiac procedure (e.g., coronary artery bypass graft surgery or transcatheter aortic valve replacement). In PRECOVERY, patients randomized to the intervention group participate in a 2-week multimodal prehabilitation intervention conducted in selected cardiac-specific rehabilitation facilities. The multimodal prehabilitation includes seven modules: exercise therapy, occupational therapy, cognitive training, psychosocial intervention, disease-specific education, education with relatives, and nutritional intervention. Participants in the control group receive standard medical care. The co-primary outcomes are quality of life (QoL) and mortality after 12 months. QoL will be measured by the EuroQol 5-dimensional questionnaire (EQ-5D-5L). A health economic evaluation using health insurance data will measure cost-effectiveness. A mixed-methods process evaluation will accompany the randomized, controlled trial to evaluate dose, reach, fidelity and adaptions of the intervention. DISCUSSION: In this study, we investigate whether a tailored prehabilitation program can improve long-term survival, QoL and functional capacity. Additionally, we will analyze whether the intervention is cost-effective. This is the largest cardiac prehabilitation trial targeting the wide implementation of a new form of care for geriatric cardiac patients. TRIAL REGISTRATION: German Clinical Trials Register (DRKS; http://www.drks.de ; DRKS00030526). Registered on 30 January 2023.

Moving Knowledge Acquisition From the Lecture Hall to the Student Home: A Prospective Intervention Study.

BACKGROUND: Podcasts are popular with medical students, but the impact of podcast use on learning outcomes in undergraduate medical education has not been studied in detail. OBJECTIVE: Our aim was to assess the impact of podcasts accompanied by quiz questions and lecture attendance on short- and medium-term knowledge retention. METHODS: Students enrolled for a cardio-respiratory teaching module were asked to prepare for 10 specific lectures by watching podcasts and submitting answers to related quiz questions before attending live lectures. Performance on the same questions was assessed in a surprise test and a retention test. RESULTS: Watching podcasts and submitting answers to quiz questions (versus no podcast/quiz use) was associated with significantly better test performance in all items in the surprise test and 7 items in the retention test. Lecture attendance (versus no attendance) was associated with higher test performance in 3 items and 1 item, respectively. In a linear regression analysis adjusted for age, gender, and overall performance levels, both podcast/quiz use and lecture attendance were significant predictors of student performance. However, the variance explained by podcast/quiz use was greater than the variance explained by lecture attendance in the surprise test (38.7% vs. 2.2%) and retention test (19.1% vs. 4.0%). CONCLUSIONS: When used in conjunction with quiz questions, podcasts have the potential to foster knowledge acquisition and retention over and above the effect of live lectures.

While systolic cardiomyocyte function is preserved, diastolic myocyte function and recovery from acidosis are impaired in CaMKIIδ-KO mice.

OBJECTIVE: CaMKII contributes to impaired contractility in heart failure by inducing SR Ca(2+)-leak. CaMKII-inhibition in the heart was suggested to be a novel therapeutic principle. Different CaMKII isoforms exist. Specifically targeting CaMKIIδ, the dominant isoform in the heart, could be of therapeutic potential without impairing other CaMKII isoforms. RATIONALE: We investigated whether cardiomyocyte function is affected by isoform-specific knockout (KO) of CaMKIIδ under basal conditions and upon stress, i.e. upon ß-adrenergic stimulation and during acidosis. RESULTS: Systolic cardiac function was largely preserved in the KO in vivo (echocardiography) corresponding to unchanged Ca(2+)-transient amplitudes and isolated myocyte contractility in vitro. CaMKII activity was dramatically reduced while phosphatase-1 inhibitor-1 was significantly increased. Surprisingly, while diastolic Ca(2+)-elimination was slower in KO most likely due to decreased phospholamban Thr-17 phosphorylation, frequency-dependent acceleration of relaxation was still present. Despite decreased SR Ca(2+)-reuptake at lower frequencies, SR Ca(2+)-content was not diminished, which might be due to reduced diastolic SR Ca(2+)-loss in the KO as a consequence of lower RyR Ser-2815 phosphorylation. Challenging KO myocytes with isoproterenol showed intact inotropic and lusitropic responses. During acidosis, SR Ca(2+)-reuptake and SR Ca(2+)-loading were significantly impaired in KO, resulting in an inability to maintain systolic Ca(2+)-transients during acidosis and impaired recovery. CONCLUSIONS: Inhibition of CaMKIIδ appears to be safe under basal physiologic conditions. Specific conditions exist (e.g. during acidosis) under which CaMKII-inhibition might not be helpful or even detrimental. These conditions will have to be more clearly defined before CaMKII inhibition is used therapeutically.

Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging.

Phosphatase inhibitor-1 (I-1) is a distal amplifier element of beta-adrenergic signaling that functions by preventing dephosphorylation of downstream targets. I-1 is downregulated in human failing hearts, while overexpression of a constitutively active mutant form (I-1c) reverses contractile dysfunction in mouse failing hearts, suggesting that I-1c may be a candidate for gene therapy. We generated mice with conditional cardiomyocyte-restricted expression of I-1c (referred to herein as dTGI-1c mice) on an I-1-deficient background. Young adult dTGI-1c mice exhibited enhanced cardiac contractility but exaggerated contractile dysfunction and ventricular dilation upon catecholamine infusion. Telemetric ECG recordings revealed typical catecholamine-induced ventricular tachycardia and sudden death. Doxycycline feeding switched off expression of cardiomyocyte-restricted I-1c and reversed all abnormalities. Hearts from dTGI-1c mice showed hyperphosphorylation of phospholamban and the ryanodine receptor, and this was associated with an increased number of catecholamine-induced Ca2+ sparks in isolated myocytes. Aged dTGI-1c mice spontaneously developed a cardiomyopathic phenotype. These data were confirmed in a second independent transgenic mouse line, expressing a full-length I-1 mutant that could not be phosphorylated and thereby inactivated by PKC-alpha (I-1S67A). In conclusion, conditional expression of I-1c or I-1S67A enhanced steady-state phosphorylation of 2 key Ca2+-regulating sarcoplasmic reticulum enzymes. This was associated with increased contractile function in young animals but also with arrhythmias and cardiomyopathy after adrenergic stress and with aging. These data should be considered in the development of novel therapies for heart failure.

Calcium/calmodulin-dependent protein kinase II contributes to cardiac arrhythmogenesis in heart failure.

BACKGROUND: Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias. We hypothesized that CaMKII contributes to arrhythmias and underlying cellular events and that inhibition of CaMKII reduces cardiac arrhythmogenesis in vitro and in vivo. METHODS AND RESULTS: Under baseline conditions, isolated cardiac myocytes from TG mice showed an increased incidence of early afterdepolarizations compared with wild-type myocytes (P<0.05). CaMKII inhibition (AIP) completely abolished these afterdepolarizations in TG cells (P<0.05). Increasing intracellular Ca stores using ISO (10(-8) M) induced a larger amount of delayed afterdepolarizations and spontaneous action potentials in TG compared with wild-type cells (P<0.05). This seems to be due to an increased sarcoplasmic reticulum (SR) Ca leak because diastolic [Ca](i) rose clearly on ISO in TG but not in wild-type cells (+20+/-5% versus +3+/-4% at 10(-6) M ISO, P<0.05). In parallel, SR Ca leak assessed by spontaneous SR Ca release events showed an increased Ca spark frequency (3.9+/-0.5 versus 2.0+/-0.4 sparks per 100 microm(-1).s(-1), P<0.05). However, CaMKII inhibition (either pharmacologically using KN-93 or genetically using an isoform-specific CaMKIIdelta-knockout mouse model) significantly reduced SR Ca spark frequency, although this rather increased SR Ca content. In parallel, ISO increased the incidence of early (54% versus 4%, P<0.05) and late (86% versus 43%, P<0.05) nonstimulated events in TG versus wild-type myocytes, but CaMKII inhibition (KN-93 and KO) reduced these proarrhythmogenic events (P<0.05). In addition, CaMKII inhibition in TG mice (KN-93) clearly reduced ISO-induced arrhythmias in vivo (P<0.05). CONCLUSIONS: We conclude that CaMKII contributes to cardiac arrhythmogenesis in TG CaMKIIdelta(C) mice having heart failure and suggest the increased SR Ca leak as an important mechanism. Moreover, CaMKII inhibition reduces cardiac arrhythmias in vitro and in vivo and may therefore indicate a potential role for future antiarrhythmic therapies warranting further studies.