Remote ischaemic conditioning (RIC) and postconditioning (PostC) are both potent activators of innate protection against ischaemia-reperfusion injury and have demonstrated cardioprotection in ...experimental and clinical ST-elevation myocardial infarction (STEMI) trials. However, their combined effects have not been studied in detail. The aim of this study was to evaluate if the co-application of intrahospital RIC and PostC has a more powerful effect on myocardial salvage compared with either PostC alone or control.
This prospective, controlled, single-centre study randomized 696 STEMI patients to one of the following three groups: (i) combined intrahospital RIC + PostC in addition to primary percutaneous coronary intervention (PCI); (ii) PostC in addition to PCI; and (iii) conventional PCI (control). The primary endpoint myocardial salvage index was assessed by cardiac magnetic resonance (CMR) imaging within 3 days after infarction. Secondary endpoints included infarct size and microvascular obstruction (MVO) assessed by CMR. The combined clinical endpoint consisted of death, reinfarction, and new congestive heart failure within 6 months. The primary endpoint myocardial salvage index was significantly greater in the combined RIC + PostC group when compared with the control group (49 interquartile range 30-72 vs. 40 interquartile range 16-68, P = 0.02). Postconditioning alone failed to improve myocardial salvage when compared with conventional PCI (P = 0.39). The secondary endpoints, including infarct size and MVO, showed no significant differences between groups. Clinical follow-up at 6 months revealed no differences in the combined clinical endpoint between groups (P = 0.44).
Combined intrahospital RIC + PostC in conjunction with PCI in STEMI significantly improves myocardial salvage in comparison with control and PostC.
NCT02158468.
Abstract Objectives This study aimed to assess characteristics including endomyocardial biopsy and outcome of patients with methamphetamine (MA)-associated cardiomyopathy in a series of patients ...treated in Germany. Background MA abuse is an increasing problem worldwide. Methods The cases of 30 consecutive MA-abusing patients with a left ventricular (LV) ejection fraction of <40% and endomyocardial biopsy performed at initial diagnosis were analyzed. Baseline characteristics were collected retrospectively, whereas follow-up was prospective. The primary endpoint was a composite of death, nonfatal stroke, and rehospitalization for heart failure. Results Patients were 30.3 ± 1.9 years of age, predominantly male (93.3%), and highly symptomatic; 83.3% had New York Heart Association functional class III or IV dyspnea. Echocardiography revealed marked LV dilatation (mean LV end-diastolic diameter 67.1 ± 7.4 mm) and impaired LV ejection fraction (mean 19 ± 6%). One-third of the patients had intraventricular thrombi. Endomyocardial biopsy revealed markers of inflammation and fibrosis; the fibrosis correlated with the duration of MA abuse. At follow-up, discontinuation of MA abuse together with medical therapy partially improved cardiac function (LV ejection fraction, 19 ± 6 vs. 43 ± 13; p < 0.001) and symptoms (p = 0.056), whereas patients with continued abuse did not show any improvement. The improvement in cardiac function was independently associated with the extent of fibrosis. The primary endpoint occurred more often in patients with continued MA abuse (57.1% vs. 17.4%; p = 0.037). Conclusions MA-associated cardiomyopathy is characterized by severe heart failure and depressed cardiac function. The extent of myocardial fibrosis seems to predict the recoverability of LV function. Cessation of MA abuse is associated with improvement in cardiac function and symptoms, whereas continued MA abuse leads to ongoing heart failure and worse outcome.
Besides structural alterations in the myocardium, heart failure with preserved ejection fraction (HFpEF) is also associated with molecular and physiological alterations of the peripheral skeletal ...muscles (SKM) contributing to exercise intolerance often seen in HFpEF patients. Recently, the use of Sodium-Glucose-Transporter 2 inhibitors (SGLT2i) in clinical studies provided evidence for a significant reduction in the combined risk of cardiovascular death or hospitalization for HFpEF. The present study aimed to further elucidate the impact of Empagliflozin (Empa) on: (1) SKM function and metabolism and (2) mitochondrial function in an established HFpEF rat model. At the age of 24 weeks, obese ZSF1 rats were randomized either receiving standard care or Empa in the drinking water. ZSF1 lean animals served as healthy controls. After 8 weeks of treatment, echocardiography and SKM contractility were performed. Mitochondrial function was assessed in saponin skinned fibers and SKM tissue was snap frozen for molecular analyses. HFpEF was evident in the obese animals when compared to lean—increased E/é and preserved left ventricular ejection fraction. Empa treatment significantly improved E/é and resulted in improved SKM contractility with reduced intramuscular lipid content. Better mitochondrial function (mainly in complex IV) with only minor modulation of atrophy-related proteins was seen after Empa treatment. The results clearly documented a beneficial effect of Empa on SKM function in the present HFpEF model. These effects were accompanied by positive effects on mitochondrial function possibly modulating SKM function.
In a multivariate binary logistic regression analysis, chronic hemodialysis (hazard ratio HR: 8.37; 95% confidence interval CI: 2.54 to 27.63; p < 0.001) and peripheral artery disease (HR: 3.77; 95% ...CI: 1.88 to 7.58; p < 0.001) remained the only independent predictors for developing IE. Negative imaging 15/47 (31.9) Total patients with affected prosthetic valve 22/47 (46.8) Vegetation only on prosthetic valve 12/47 (25.5) Vegetation on prosthetic valve and other valve 7/47 (14.9) Vegetation on prosthetic valve and PM/ICD lead 1/47 (2.1) Vegetation on prosthetic valve, PM/ICD lead and other valve 2/47 (4.3) Paravalvular abscess 9/47 (19.1) Vegetation on other valve than prosthetic valve 4/47 (8.5) Vegetation on PM/ICD lead 3/47 (6.4) Vegetation on PM/ICD lead and other valve 3/47 (6.4) Table 1 Characteristics of Patients Without and With Development of Infective Endocarditis Values are mean ± SD, median (interquartile range), or n (%).AR = aortic regurgitation; CKD = chronic kidney disease stage; COPD = chronic obstructive lung disease; ICD = implantable cardioverter-defibrillator; IE = infective endocarditis; PAD = peripheral artery disease; PM = pacemaker; STS = Society of Thoracic Surgeons; TOE = transesophageal echocardiography; ViV = valve-in-valve.
A reduction in number and function of endothelial progenitor cells (EPCs) occurs in both physiologic aging and chronic heart failure (CHF). We assessed whether disease and aging have additive effects ...on EPCs or whether beneficial effects of exercise training are diminished in old age.
We randomized 60 patients with stable CHF and 60 referent controls to a training or a control group. To detect possible aging effects we included subjects below 55 (young) and above 65 years (older). Subjects in the training group exercised four times daily at 60% to 70% of VO2max for four weeks under supervision. At baseline and after the intervention the number and function of EPCs were assessed.
As compared with young referent controls, older referent controls showed at baseline a reduced EPC number (young: 190 ± 37 CD34/KDR positive cells/ml blood; older: 131 ± 26 CD34/KDR positive cells/ml blood; p < 0.05) and function (young: 230 ± 41 migrated cells/1000 plated cells; older: 185 ± 28 cells/1000 plated cells; p < 0.05). In young and older CHF patients EPC-number (young: 85 ± 21 CD34/KDR positive cells/ml blood; older: 78 ± 20 CD34/KDR positive cells/ml blood) and EPC-function (young: 113 ± 26 cells/1000 plated cells; older: 120 ± 27 cells/1000 plated cells) were impaired. As a result of exercise training, EPC function improved by 24% in older referent controls (p < 0.05), while it remained unchanged in young training referent controls and controls respectively. In young and older patients with CHF four weeks of exercise training resulted in a significant improvement in EPC numbers and EPC function (young: number +66% function +43%; p < 0.05; older: number +69% function +36%; p < 0.05). These results were accompanied by a significant increase in flow mediated dilatation in the training groups of young/older CHF patients and in older referent controls.
Four weeks of exercise training are effective in improving EPC number and EPC function in CHF patients. These training effects were not impaired among older patients, emphasizing the potentials of rehabilitation interventions in a patient group where CHF has a high prevalence.
Heart failure with preserved ejection fraction (HFpEF) is characterized by biomechanically dysfunctional cardiomyocytes. Underlying cellular changes include perturbed myocardial titin expression and ...titin hypophosphorylation leading to titin filament stiffening. Beside these well-studied alterations at the cardiomyocyte level, exercise intolerance is another hallmark of HFpEF caused by molecular alterations in skeletal muscle (SKM). Currently, there is a lack of data regarding titin modulation in the SKM of HFpEF. Therefore, the aim of the present study was to analyze molecular alterations in limb SKM (tibialis anterior (TA)) and in the diaphragm (Dia), as a more central SKM, with a focus on titin, titin phosphorylation, and contraction-regulating proteins. This study was performed with muscle tissue, obtained from 32-week old female ZSF-1 rats, an established a HFpEF rat model. Our results showed a hyperphosphorylation of titin in limb SKM, based on enhanced phosphorylation at the PEVK region, which is known to lead to titin filament stiffening. This hyperphosphorylation could be reversed by high-intensity interval training (HIIT). Additionally, a negative correlation occurring between the phosphorylation state of titin and the muscle force in the limb SKM was evident. For the Dia, no alterations in the phosphorylation state of titin could be detected. Supported by data of previous studies, this suggests an exercise effect of the Dia in HFpEF. Regarding the expression of contraction regulating proteins, significant differences between Dia and limb SKM could be detected, supporting muscle atrophy and dysfunction in limb SKM, but not in the Dia. Altogether, these data suggest a correlation between titin stiffening and the appearance of exercise intolerance in HFpEF, as well as a differential regulation between different SKM groups.
Remote proctoring by advanced digital technologies may help to overcome pandemic, geographic, and resource-related constraints for mentoring and educating interventional cardiology skills. We present ...a case series of patients undergoing high-risk percutaneous coronary intervention (HR-PCI) with mechanical circulatory support (MCS) guided by remote proctoring to gain insights into a streaming technology platform with regard to video/audio quality, visibility of all structural and imaging details, and delay in transmission. According to our experience, remote proctoring appears to be a reliable, quick, and resource-conserving way to disseminate, educate and improve MCS-supported HR-PCI with implications far beyond the COVID-19 pandemic.
Background
About half of heart failure (HF) patients, while having preserved left ventricular function, suffer from diastolic dysfunction (so‐called HFpEF). No specific therapeutics are available for ...HFpEF in contrast to HF where reduced ejection fractions (HFrEF) can be treated pharmacologically. Myocardial titin filament stiffening, endothelial dysfunction, and skeletal muscle (SKM) myopathy are suspected to contribute to HFpEF genesis. We previously described small molecules interfering with MuRF1 target recognition thereby attenuating SKM myopathy and dysfunction in HFrEF animal models. The aim of the present study was to test the efficacy of one small molecule (MyoMed‐205) in HFpEF and to describe molecular changes elicited by MyoMed‐205.
Methods
Twenty‐week‐old female obese ZSF1 rats received the MuRF1 inhibitor MyoMed‐205 for 12 weeks; a comparison was made to age‐matched untreated ZSF1‐lean (healthy) and obese rats as controls. LV (left ventricle) function was assessed by echocardiography and by invasive haemodynamic measurements until week 32. At week 32, SKM and endothelial functions were measured and tissues collected for molecular analyses. Proteome‐wide analysis followed by WBs and RT‐PCR was applied to identify specific genes and affected molecular pathways. MuRF1 knockout mice (MuRF1‐KO) SKM tissues were included to validate MuRF1‐specificity.
Results
By week 32, untreated obese rats had normal LV ejection fraction but augmented E/e′ ratios and increased end diastolic pressure and myocardial fibrosis, all typical features of HFpEF. Furthermore, SKM myopathy (both atrophy and force loss) and endothelial dysfunction were detected. In contrast, MyoMed‐205 treated rats had markedly improved diastolic function, less myocardial fibrosis, reduced SKM myopathy, and increased SKM function. SKM extracts from MyoMed‐205 treated rats had reduced MuRF1 content and lowered total muscle protein ubiquitination. In addition, proteomic profiling identified eight proteins to respond specifically to MyoMed‐205 treatment. Five out of these eight proteins are involved in mitochondrial metabolism, dynamics, or autophagy. Consistent with the mitochondria being a MyoMed‐205 target, the synthesis of mitochondrial respiratory chain complexes I + II was increased in treated rats. MuRF1‐KO SKM controls also had elevated mitochondrial complex I and II activities, also suggesting mitochondrial activity regulation by MuRF1.
Conclusions
MyoMed‐205 improved myocardial diastolic function and prevented SKM atrophy/function in the ZSF1 animal model of HFpEF. Mechanistically, SKM benefited from an attenuated ubiquitin proteasome system and augmented synthesis/activity of proteins of the mitochondrial respiratory chain while the myocardium seemed to benefit from reduced titin modifications and fibrosis.
Background: Transcatheter left atrial appendage (LAA) closure is an alternative therapy for stroke prevention in atrial fibrillation (AF) patients. However; real-world efficacy, safety and ...complications have yet to be investigated. We sought to determine the procedural outcomes and potential complications of LAA closure in routine clinical practice at a high-volume center. Methods and Results: The study group comprised 179 patients (105 males; 72.7±9.0 years) with AF undergoing LAA closure at a single center in Germany. The rate of successful implantation was 98.9% (2 patients did not undergo implantation) and the overall procedure-related complication rate was 11.2% (major: 3.3%: tamponade 2; possibility of transient ischemic attack (TIA) 1; device dislocation 3; minor: 7.8%: pericardial effusion 2; air embolization with transient ST segment elevation 3; thrombus on device/sheath 3; puncture complications 5). At 45 days; 99.4% showed successful sealing of the LAA and 94.5% discontinued oral anticoagulation (OAC). TIA occurred in 2 patients during 6-month follow-up; but no cases of stroke were reported. There were no hemorrhagic stroke or device-related deaths. Only 1 patient was hospitalized with traumatic subdural hematoma. Minor bleeding was reported in 5 patients. Conclusions: Transcatheter LAA closure in a high-volume center is safe and feasible. Life-threatening complications are rare. Discontinuation of OAC 45 days after implantation was also safe. (Circ J 2014; 78: 619–624)
PDF
