Mitral valve replacement versus repair for severe mitral regurgitation in patients with reduced left ventricular ejection fraction

Objective: This study compares early and long-term outcomes following mitral valve (MV) repair and replacement in patients with mitral regurgitation (MR) and reduced left ventricular ejection fraction (LVEF).

Methods: Patients with primary or secondary MR and LVEF <50% who underwent MV replacement or repair (with/without atrial septal defect closure and/or atrial fibrillation ablation) between 2005 and 2017 at our center were retrospectively analyzed using unadjusted and propensity score matching techniques (42 pairs).

Results: A total of 356 patients with either primary (n = 162 [45.5%]) or secondary MR (n = 194 [54.5%]) and LVEF <50% underwent MV repair (n = 293 [82.3%]) or replacement (n = 63 [17.7%]) during the study period. In-hospital mortality was 0.3% (repair) and 1.6% (replacement) in the unmatched cohort (P = .32); there were no in-hospital deaths after matching. Estimated survival was 72.8% (repair) versus 50.1% (replacement) at 8 years in the unmatched (P < .001), and 64.3% (repair) versus 50.7% (replacement) in the matched groups (P = .028). Eight-year cumulative incidence of reoperation was 7.0% and 11.6% in unmatched (P = .28), and 9.9% and 12.7% in matched (P = .69) repair and replacement groups, respectively. Markedly reduced LVEF (<40%) was among the independent predictors of long-term mortality (hazard ratio, 1.7; 95% CI, 1.2-2.4; P = .002). In secondary MR, MV repair showed an 8-year survival benefit over replacement (65.1% vs 44.6%; P = .002), with no difference in reoperation rate (11.6% [repair] vs 17.0% [replacement]; P = .11).

Conclusions: MV repair performed in primary or secondary MR and reduced LVEF provides superior long-term results compared with replacement. Severe LV dysfunction is a significant predictor of reduced survival following MV surgery.

Keywords: heart failure; mitral regurgitation; mitral valve repair; mitral valve replacement.

Cutibacterium acnes infective endocarditis-an emerging pathogen

Objectives: The study aimed to review a multicentre experience of patients undergoing surgical intervention for infective endocarditis caused by Cutibacterium acnes and to analyse the diagnostic challenges and operative results.

Methods: We retrospectively reviewed 8812 patients undergoing cardiac surgery for endocarditis at 12 cardiac surgical departments across Germany. The overall population was divided based on the type of endocarditis (i.e. native and prosthetic valve endocarditis). Primary outcomes were in-hospital mortality, 1- and 5-year survival.

Results: Cutibacterium acnes caused endocarditis in 269 patients (3.1%). Median age was 65 years (54-72 years) and 237 (88.1%) were male. We observed significantly higher rates of native valve endocarditis in patients aged 21-40, whereas prosthetic valve endocarditis was more frequent in all other age groups (P < 0.001). The median EuroSCORE II of the cohort was 10.7 (5.0-29.6), with it being significantly higher in the prosthetic valve endocarditis group (P < 0.001). Blood culture-negative infective endocarditis was initially reported in 54.3% of the patients. The in-hospital mortality was comparable between the groups (P = 0.340). Survival at 1 and 5 years was significantly higher in the native valve endocarditis group (P < 0.001).

Conclusions: Cutibacterium acnes causes native valve endocarditis, especially in younger patients. The incidence of endocarditis caused by C.acnes is alarming and is at par with well-known endocarditis pathogens such as the HACEK group. The pathogen has a low virulence and presents with a rather indolent course. The diagnosis of C.acnes endocarditis is challenging and requires a multimodal specialized approach. Surgical treatment is associated with acceptable outcomes.

Keywords: Cutibacterium acnes; Infective endocarditis; Valvular heart disease.

Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies

The left and right ventricles of the human heart are functionally and developmentally distinct such that genetic or acquired insults can cause dysfunction in one or both ventricles resulting in heart failure. To better understand ventricle-specific molecular changes influencing heart failure development, we first performed unbiased quantitative mass spectrometry on pre-mortem non-diseased human myocardium to compare the metabolome and proteome between the normal left and right ventricles. Constituents of gluconeogenesis, glycolysis, lipogenesis, lipolysis, fatty acid catabolism, the citrate cycle and oxidative phosphorylation were down-regulated in the left ventricle, while glycogenesis, pyruvate and ketone metabolism were up-regulated. Inter-ventricular significance of these metabolic pathways was then found to be diminished within end-stage dilated cardiomyopathy and ischaemic cardiomyopathy, while heart failure-associated pathways were increased in the left ventricle relative to the right within ischaemic cardiomyopathy, such as fluid sheer-stress, increased glutamine-glutamate ratio, and down-regulation of contractile proteins, indicating a left ventricular pathological bias.

Myocardial Posttranscriptional Landscape in Peripartum Cardiomyopathy

Background: Pregnancy imposes significant cardiovascular adaptations, including progressive increases in plasma volume and cardiac output. For most women, this physiological adaptation resolves at the end of pregnancy, but some women develop pathological dilatation and ultimately heart failure late in pregnancy or in the postpartum period, manifesting as peripartum cardiomyopathy (PPCM). Despite the mortality risk of this form of heart failure, the molecular mechanisms underlying PPCM have not been extensively examined in human hearts.

Methods: Protein and metabolite profiles from left ventricular tissue of end-stage PPCM patients (N=6-7) were compared with dilated cardiomyopathy (DCM; N=5-6) and nonfailing donors (N=7-18) using unbiased quantitative mass spectrometry. All samples were derived from the Sydney Heart Bank. Data are available via ProteomeXchange with identifier PXD055986. Differential protein expression and metabolite abundance and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed.

Results: Proteomic analysis identified 2 proteins, SBSPON (somatomedin B and thrombospondin type 1 domain-containing protein precursor) and TNS3 (tensin 3), that were uniquely downregulated in PPCM. SBSPON, an extracellular matrix protein, and TNS3, involved in actin remodeling and cell signaling, may contribute to impaired tissue remodeling and fibrosis in PPCM. Metabolomic analysis revealed elevated levels of homogentisate and deoxycholate and reduced levels of lactate and alanine in PPCM, indicating disrupted metabolic pathways and glucose utilization. Both PPCM and DCM shared pathways related to inflammation, immune responses, and signal transduction. However, thyroid hormone signaling was notably reduced in PPCM, affecting contractility and calcium handling through altered expression of PLN (phospholamban) and Sarcoendoplasmic Reticulum Calcium ATPase (SERCA). Enhanced endoplasmic reticulum stress and altered endocytosis pathways in PPCM suggested additional mechanisms of energy metabolism disruption.

Conclusions: The present study reveals unique posttranslational molecular features of the PPCM myocardium, which mediates cellular and metabolic remodeling, and holds promise as potential targets for therapeutic intervention.

Aortic and Mitral Valve Endocarditis-Simply Left-Sided Endocarditis or Different Entities Requiring Individual Consideration?-Insights from the CAMPAIGN Database

Background: Aortic valve infective endocarditis (AV-IE) and mitral valve infective endocarditis (MV-IE) are often grouped together as one entity: left-sided endocarditis. However, there are significant differences between the valves in terms of anatomy, physiology, pressure, and calcification tendency. This study aimed to compare AV-IE and MV-IE in terms of patient characteristics, pathogen profiles, postoperative outcomes, and predictors of mortality.

Methods: We retrospectively analyzed data from 3899 patients operated on for isolated AV-IE or MV-IE in six German cardiac surgery centers between 1994 and 2018. Univariable and multivariable analyses were performed to analyze the risk factors for 30 day and 1 year mortality. A Log-rank test was used to test for differences in long-term mortality.

Results: Patients with MV-IE were more likely to be female (41.1% vs. 20.3%.; p < 0.001). Vegetation was detected more frequently in the MV-IE group (66.6% vs. 57.1%; p < 0.001). Accordingly, the rates of cerebral embolic events (25.4% vs. 17.7%; p < 0.001) and stroke (28.2% vs. 19.3%; p < 0.001) were higher in the MV-IE group. Staphylococci had a higher prevalence in the MV-IE group (50.2% vs. 36.4%; p < 0.001). Patients with MV-IE had comparable 30 day mortality (16.7% vs. 14.6%; p = 0.095) but significantly higher 1 year mortality (35.3% vs. 29.0%; p < 0.001) than those with AV-IE. Kaplan-Meier survival analysis showed significantly lower long-term survival in patients with MV-IE (log-rank p < 0.001).

Conclusions: Due to the relevant differences between MV-IE and AV-IE, it might be useful to provide individualized, valve-specific guideline recommendations rather than general recommendations for left-sided IE.

A comparison of fixation and immunofluorescence protocols for successful reproducibility and improved signal in human left ventricle cardiac tissue

Immunohistochemistry (IHC) and immunofluorescence (IF) are crucial techniques for studying cardiac physiology and disease. The accuracy of these techniques is dependent on various aspects of sample preparation and processing. However, standardised protocols for sample preparation of tissues, particularly for fresh-frozen human left ventricle (LV) tissue, have yet to be established and could potentially lead to differences in staining and interpretation. Thus, this study aimed to optimise the reproducibility and quality of IF staining in fresh-frozen human LV tissue by systematically investigating crucial aspects of the sample preparation process. To achieve this, we subjected fresh-frozen human LV tissue to different fixation protocols, primary antibody incubation temperatures, antibody penetration reagents, and fluorescent probes. We found that neutral buffered formalin fixation reduced image artefacts and improved antibody specificity compared to both methanol and acetone fixation. Additionally, incubating primary antibodies at 37°C for 3 h improved fluorescence intensity compared to the commonly practised 4°C overnight incubation. Furthermore, we found that DeepLabel, an antibody penetration reagent, and smaller probes, such as fragmented antibodies and Affimers, improved the visualisation depth of cardiac structures. DeepLabel also improved antibody penetration in CUBIC cleared thick LV tissue fragments. Thus, our data underscores the importance of standardised protocols in IF staining and provides various means of improving staining quality. In addition to contributing to cardiac research by providing methodologies for IF, the findings and processes presented herein also establish a framework by which staining of other tissues may be optimised.

Impact of Complex Anatomy and Patient Risk Profile in Minimally Invasive Mitral Valve Surgery

Background: We aimed to assess the impact of complex mitral valve disease and patient risk profile on operative outcomes in the large cohort of the Mini-Mitral International Registry.

Methods: Patients were assigned to categories of complex degenerative mitral valve regurgitation (DMR; bileaflet or anterior mitral leaflet prolapse/flail) and simple DMR (posterior mitral leaflet prolapse/flail). Subgroup analyses was performed in low-risk (EuroSCORE II <8%) and high-risk (EuroSCORE II >8%) cohorts. A logistic regression model was applied to investigate the impact of valve anatomy and patient risk factors on valve repair rate and operative risk.

Results: The study cohort consisted of 4524 patients with DMR (complex DMR, 1296; simple DMR, 3228). Valve repair rate was 87.3% and 91% in complex DMR and simple DMR, respectively. Predictors of valve replacement were anterior leaflet prolapse/flail, bileaflet flail, female sex, age, and reoperation, whereas Barlow disease was protective. Clinical results were comparable between complex DMR and simple DMR. On subgroup analyses, high-risk patients showed less satisfactory outcomes with respect to both the valve repair and operative mortality rates.

Conclusions: Our findings suggest that complex DMR can be satisfactorily addressed by minimally invasive techniques. However, whereas complex disease was associated with low operative risk, anterior leaflet lesions and bileaflet flail remain negative predictors of successful valve repair. Conversely, valve repair rate was less satisfactory in high-risk patients, regardless of DMR complexity.

Indocyanine Green (ICG): A Versatile Tool in Enhancing Precision in Minimally Invasive Thoracic Surgery

Intraoperative fluorescence imaging using indocyanine green (ICG) is an innovative and safe tool in minimally invasive thoracic surgery. It provides real-time imaging capabilities that can enhance surgical precision. We describe several clinical uses of ICG including intersegmental plane identification, thoracic duct injury localisation, anomalous systemic artery identification in pulmonary sequestration, phrenic nerve identification, and sentinel lymph node mapping. Successful visualisation of ICG was achieved to identify intra-thoracic anatomical structures and boundaries, allowing for safe and precise dissection.

Pearls and Pitfalls of Epicardial Echocardiography for Implantation of Impella CP Devices in Ovine Models

The Impella CP is a percutaneously inserted temporary left ventricular assist device used in clinical practice and in translational research into cardiogenic shock, perioperative cardiac surgery, acute cardiac failure and mechanical circulatory support. Fluoroscopic guidance is usually used for insertion of an Impella, thus limiting insertion to within catheterization laboratories. Transthoracic, transoesophageal and intracardiac echocardiography have been reported to guide Impella CP implantation with identified specific limitations stemming from the surgical, anatomical and equipment factors. We conducted translational prospective descriptive feasibility investigation as a part of two other hemodynamic Impella studies. It showed the successful application of epicardial echocardiographic scanning for implantation of Impella CP devices in ovine models, from which details of the technique and identified pitfalls are described with practical solutions for future investigators and clinicians. Many described findings are relevant to any other echocardiographic techniques when adequate imaging of the Impella and relevant anatomical structures is achievable.

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