An important complication of prolonged support of the left ventricle with an assist device when implanted in patients with heart failure is unloading-induced cardiac atrophy. Our recent study suggested that sex-linked differences in the development of atrophy induced by heterotopic heart transplantation (HTX) do exist, however, the role of the environmental conditions dependent on plasma concentrations of sex hormones remains elusive. We aimed to compare the course of HTX-induced cardiac atrophy in male and female rats after gonadectomy with substitution of steroid hormones of the opposite sex. In a separate series of experiments, we evaluated the course of unloading-induced cardiac atrophy in the female heart transplanted into a male recipient and vice versa. Cardiac atrophy was assessed as the ratio of the transplanted heart weight to native heart weight (HW), which was determined 14 days after HTX. In female rats, studied in both experimental variants, HTx resulted in significantly smaller decreases in whole HW when compared to those observed in male rats exposed to the same experimental conditions (-9 ± 1 and - 11 + 1 vs. -44 ± 2 and -42 ± 2 %, p?0.05 in both cases). The dynamic of changes in left and right ventricle was similar as in the whole HW. Our results show that the process of unloading-induced cardiac atrophy exhibits important sex-linked differences and that attenuation of this process in female rats cannot be simply ascribed to the protective effects of estradiol or to the absence of deleterious actions of testosterone. Keywords: Cardiac atrophy, Sex differences, Gonadectomy, Hormonal substitution, Heterotopic heart transplantation, Mechanical heart unloading.
- MeSH
- Atrophy * MeSH
- Estradiol blood MeSH
- Transplantation, Heterotopic * MeSH
- Rats MeSH
- Sex Characteristics * MeSH
- Gonadal Steroid Hormones * blood MeSH
- Rats, Wistar MeSH
- Heart MeSH
- Testosterone blood MeSH
- Heart Transplantation * adverse effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Percutaneous active mechanical circulatory support (MCS) devices are being increasingly used in the treatment of acute myocardial infarction-related cardiogenic shock (AMICS) despite conflicting evidence regarding their effect on mortality. We aimed to ascertain the effect of early routine active percutaneous MCS versus control treatment on 6-month all-cause mortality in patients with AMICS. METHODS: In this individual patient data meta-analysis, randomised controlled trials of potential interest were identified, without language restriction, by querying the electronic databases MEDLINE via PubMed, Cochrane Central Register of Controlled Trials, and Embase, as well as ClinicalTrials.gov, up to Jan 26, 2024. All randomised trials with 6-month mortality data comparing early routine active MCS (directly in the catheterisation laboratory after randomisation) versus control in patients with AMICS were included. The primary outcome was 6-month all-cause mortality in patients with AMICS treated with early routine active percutaneous MCS versus control, with a focus on device type (loading, such as venoarterial extracorporeal membrane oxygenation [VA-ECMO] vs unloading) and patient selection. Hazard ratios (HRs) of the primary outcome measure were calculated using Cox regression models. This study is registered with PROSPERO, CRD42024504295. FINDINGS: Nine reports of randomised controlled trials (n=1114 patients) were evaluated in detail. Overall, four randomised controlled trials (n=611 patients) compared VA-ECMO with a control treatment and five randomised controlled trials (n=503 patients) compared left ventricular unloading devices with a control treatment. Two randomised controlled trials also included patients who did not have AMICS, who were excluded (55 patients [44 who were treated with VA-ECMO and 11 who were treated with a left ventricular unloading device]). The median patient age was 65 years (IQR 57-73); 845 (79·9%) of 1058 patients with data were male and 213 (20·1%) were female. No significant benefit of early unselected MCS use on 6-month mortality was noted (HR 0·87 [95% CI 0·74-1·03]; p=0·10). No significant differences were observed for left ventricular unloading devices versus control (0·80 [0·62-1·02]; p=0·075), and loading devices also had no effect on mortality (0·93 [0·75-1·17]; p=0·55). Patients with ST-elevation cardiogenic shock without risk of hypoxic brain injury had a reduction in mortality with MCS use (0·77 [0·61-0·97]; p=0·024). Major bleeding (odds ratio 2·64 [95% CI 1·91-3·65]) and vascular complications (4·43 [2·37-8·26]) were more frequent with MCS use than with control. INTERPRETATION: The use of active MCS devices in patients with AMICS did not reduce 6-month mortality (regardless of the device used) and increased major bleeding and vascular complications. However, patients with ST-elevation cardiogenic shock without risk of hypoxic brain injury had a reduction in mortality after MCS use. Therefore, the use of MCS should be restricted to certain patients only. FUNDING: The Heart Center Leipzig at Leipzig University and the Foundation Institut für Herzinfarktforschung.
- MeSH
- Myocardial Infarction * mortality complications MeSH
- Shock, Cardiogenic * therapy mortality etiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Extracorporeal Membrane Oxygenation * methods MeSH
- Follow-Up Studies MeSH
- Heart-Assist Devices * MeSH
- Randomized Controlled Trials as Topic MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
BACKGROUND: The glucagon-like peptide-1 receptor agonist, semaglutide, improved health status and reduced body weight in patients with obesity-related heart failure (HF) with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) program. Whether benefits were due to mechanical unloading or effects on HF pathobiology is uncertain. OBJECTIVES: This study sought to determine if semaglutide 2.4 mg reduced N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with obesity-related HFpEF and compare treatment responses by baseline NT-proBNP. METHODS: This was a prespecified secondary analysis of pooled data from 2 double-blind, placebo-controlled, randomized trials (STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes]) testing effects of semaglutide in patients with obesity-related HFpEF. The main outcomes were change in NT-proBNP at 52 weeks and change in the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and body weight by baseline NT-proBNP. RESULTS: In total, 1,145 patients were randomized. Semaglutide compared with placebo reduced NT-proBNP at 52 weeks (estimated treatment ratio: 0.82; 95% CI: 0.74-0.91; P = 0.0002). Improvements in health status were more pronounced in those with higher vs lower baseline NT-proBNP (estimated difference: tertile 1: 4.5 points, 95% CI: 0.8-8.2; tertile 2: 6.2 points, 95% CI: 2.4-10.0; tertile 3: 11.9 points, 95% CI: 8.1-15.7; P interaction = 0.02; baseline NT-proBNP as a continuous variable: P interaction = 0.004). Reductions in body weight were consistent across baseline NT-proBNP levels (P interaction = 0.21). CONCLUSIONS: In patients with obesity-related HFpEF, semaglutide reduced NT-proBNP. Participants with higher baseline NT-proBNP had a similar degree of weight loss but experienced larger reductions in HF-related symptoms and physical limitations with semaglutide than those with lower NT-proBNP.
- MeSH
- Double-Blind Method MeSH
- Glucagon-Like Peptides * therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Natriuretic Peptide, Brain * blood MeSH
- Obesity * blood complications drug therapy MeSH
- Peptide Fragments * blood MeSH
- Aged MeSH
- Heart Failure * drug therapy blood physiopathology MeSH
- Stroke Volume * drug effects physiology MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
No information is available about sex-related differences in unloading-induced cardiac atrophy. We aimed to compare the course of unloading-induced cardiac atrophy in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to obtain insight into the influence of sex hormones on this process. Heterotopic heart transplantation (HT((x)) was used as a model for heart unloading. Cardiac atrophy was assessed as the weight ratio of heterotopically transplanted heart weight (HW) to the native HW on days 7 and 14 after HTx in intact male and female rats. In separate experimental groups, gonadectomy was performed in male and female recipient animals 28 days before HT(x) and the course of cardiac atrophy was again evaluated on days 7 and 14 after HT(x). In intact male rats, HT(x) resulted in significantly greater decreases in whole HW when compared to intact female rats. The dynamics of the left ventricle (LV) and right ventricle (RV) atrophy after HT(x) was quite similar to that of whole hearts. Gonadectomy did not have any significant effect on the decreases in whole HW, LV, and RV weights, with similar results in male and female rats. Our results show that the development of unloading-induced cardiac atrophy is substantially reduced in female rats when compared to male rats. Since gonadectomy did not alter the course of cardiac atrophy after HTx, similarly in both male and female rats, we conclude that sex-linked differences in the development of unloading-induced cardiac atrophy are not caused by the activity of sex hormones.
The term 'mechanosensation' describes the capacity of cells to translate mechanical stimuli into the coordinated regulation of intracellular signals, cellular function, gene expression and epigenetic programming. This capacity is related not only to the sensitivity of the cells to tissue motion, but also to the decryption of tissue geometric arrangement and mechanical properties. The cardiac stroma, composed of fibroblasts, has been historically considered a mechanically passive component of the heart. However, the latest research suggests that the mechanical functions of these cells are an active and necessary component of the developmental biology programme of the heart that is involved in myocardial growth and homeostasis, and a crucial determinant of cardiac repair and disease. In this Review, we discuss the general concept of cell mechanosensation and force generation as potent regulators in heart development and pathology, and describe the integration of mechanical and biohumoral pathways predisposing the heart to fibrosis and failure. Next, we address the use of 3D culture systems to integrate tissue mechanics to mimic cardiac remodelling. Finally, we highlight the potential of mechanotherapeutic strategies, including pharmacological treatment and device-mediated left ventricular unloading, to reverse remodelling in the failing heart.
- MeSH
- Fibroblasts pathology MeSH
- Humans MeSH
- Myocardium pathology MeSH
- Ventricular Remodeling MeSH
- Heart Ventricles pathology MeSH
- Heart Failure * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
PURPOSE OF REVIEW: Cardiogenic shock (CS) therapy involving catecholamines, inotropes, fluids and revascularization is often insufficient, and short-term mortality remains 50%. Different treatment algorithms and mechanical circulatory support devices (MCS) have been increasingly used in the treatment of CS. Coronavirus disease 2019 (COVID-19) pandemic is a major challenge faced by intensive care medicine providers inevitably influencing also CS management. RECENT FINDINGS: There is a lack of prospective data as well as international consensus regarding CS classification, patient risk stratification, and MCS use. Veno-arterial extracorporeal membrane oxygenation is considered the first line MCS in refractory CS and Impella the MCS of choice for the left ventricle unloading. Several ongoing randomized trials will provide much-needed evidence for MCS use in the coming years. COVID-19 infection is associated with several cardiovascular disorders complicated by CS and more data regarding the prevalence and mortality of CS during COVID-19 infection are needed. SUMMARY: This review summarizes current trends in the use of MCS in CS and discusses differences in CS management during the COVID-19 pandemic. Careful patient selection, early MCS initiation, and comprehensive intensive care by experienced team is key to successful outcome in patients with refractory CS.
- MeSH
- COVID-19 * MeSH
- Shock, Cardiogenic therapy MeSH
- Humans MeSH
- Pandemics MeSH
- Heart-Assist Devices * MeSH
- Prospective Studies MeSH
- SARS-CoV-2 MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
The main reason for the emergency implantation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is the restoration of adequate systemic perfusion, while protecting the failing heart and promoting myocardial recovery are equally important goals. Following initial haemodynamic stabilization and often the urgent revascularization of the culprit lesion, the clinical focus is then directed towards the most efficient strategy for cardioprotection. Frequent echocardiography measurements may help to estimate the degree of unwanted left ventricular (LV) overloading during VA-ECMO. Additionally, the estimation of high LV filling pressures by Doppler echocardiography or their (in-)direct measurement using a dedicated surgical left atrial pressure line and conventional pulmonary artery catheter in a wedge position or a pigtail catheter in the left ventricle can be performed. Mechanical overload of the left ventricle is the major adverse effect and an obvious mechanistic and prognostic challenge of contemporary ECMO care. Many efforts are under way to overcome this phenomenon by LV unloading, which was effectively achieved by the current combined approach using an axial decompression device, while novel technical developments and approaches are tested and urgently anticipated. The aim of this report is to introduce in depth pathophysiological background, current concepts, and future perspectives in LV unloading strategies.
- Publication type
- Journal Article MeSH
A 19-year-old woman with no previous cardiac history was admitted to the hospital with third-degree atrioventricular block and left ventricular dysfunction. Her condition quickly deteriorated to severe biventricular failure and cardiogenic shock requiring mechanical circulatory support. An endomyocardial biopsy revealed lymphocytic myocarditis with no PCR-detectable viral genomes, with CD8 T-cell predominance and pro-inflammatory macrophage expansion shown by myocardial flow cytometry. The therapy consisted of immunosuppression (high-dose methylprednisolone) and temporary mechanical circulatory support with enhanced ability to achieve left ventricular unloading by combination of extracorporeal membrane oxygenation with Impella (ECMELLA). After 2 weeks of support, complete and sustained recovery from myocarditis was observed.
- MeSH
- CD8-Positive T-Lymphocytes MeSH
- Adult MeSH
- Immunosuppression Therapy MeSH
- Humans MeSH
- Young Adult MeSH
- Myocarditis * diagnosis etiology therapy MeSH
- Heart-Assist Devices * MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Research Support, Non-U.S. Gov't MeSH
For patients with myocardial infarct-related cardiogenic shock (CS), urgent percutaneous coronary intervention is the recommended treatment strategy to limit cardiac and systemic ischemia. However, a specific therapeutic intervention is often missing in non-ischemic CS cases. Though drug treatment with inotropes and/or vasopressors may be required to stabilize the patient initially, their ongoing use is associated with excess mortality. Coronary intervention in unstable patients often leads to further hemodynamic compromise either during or shortly after revascularization. Support devices like the intra-aortic balloon pump failed to improve clinical outcomes in infarct-related CS. Currently, more powerful and active hemodynamic support devices unloading the left ventricle such as transvalvular microaxial pumps are available and are being increasingly used. However, as for other devices large randomized trials are not yet available, and device use is based on registry data and expert consensus. In this article, a multidisciplinary group of experienced users of transvalvular microaxial pumps outlines the pathophysiological background on hemodynamic changes in CS, the available mechanical support devices, and current guideline recommendations. Furthermore, different hemodynamic situations in several case-based scenarios are used to illustrate candidate settings and to provide the theoretic and scientific rationale for left-ventricular unloading in these scenarios. Finally, organization of shock networks, monitoring, weaning, and typical complications and their prevention are discussed.
- MeSH
- Hemodynamics physiology MeSH
- Intra-Aortic Balloon Pumping methods trends MeSH
- Shock, Cardiogenic diagnosis epidemiology therapy MeSH
- Humans MeSH
- Extracorporeal Membrane Oxygenation methods trends MeSH
- Heart-Assist Devices trends MeSH
- Heart Failure diagnosis epidemiology therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Geographicals
- Europe MeSH
Slow breathing training reduces resting blood pressure, probably by modifying central autonomic control, but evidence for this is lacking. The pressor response to static handgrip exercise is a measure of autonomic control and the aim of this study was to determine whether slow breathing training modulates the pressor responses to exercise of untrained muscles. Twenty hypertensive patients trained for 8 weeks, 10 with unloaded slow breathing (Unloaded) and 10 breathing against an inspiratory load of 20 cm H(2)O (Loaded). Ten subjects were untrained controls. Subjects performed a 2 min handgrip pressor test (30 % MVC) pre- and post-training, and blood pressure and heart rate (HR) were measured before the contraction, at the end and following 2 min recovery. Resting systolic (sBP) and HR were reduced as a result of training, as reported previously. After training there was both a smaller pressor response to hand grip exercise and a more rapid recovery of sBP and HR compared to pre-training. There were no changes in the Controls and no differences between the Unloaded and Loaded groups. Combining the two training groups, the sBP response to handgrip exercise after training was reduced by 10 mm Hg (95 % CI: -7, -13) and HR by 5 bpm (95 % CI: -4, -6), all p<0.05. These results are consistent with slow breathing training modifying central mechanisms regulating cardiovascular function.
- MeSH
- Exercise physiology MeSH
- Breathing Exercises methods MeSH
- Adult MeSH
- Blood Pressure physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Blood Pressure Determination methods MeSH
- Aged MeSH
- Hand Strength physiology MeSH
- Heart Rate physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
