Prosthesis-Patient Mismatch after Aortic Valve Replacement with the Mosaic Ultra Bioprosthesis.

BACKGROUND: Several studies have reported high rates of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) with the Mosaic prosthesis. This work assesses the incidence of PPM after AVR with a modified version of the Mosaic prosthesis, the Mosaic Ultra. METHODS: We performed a retrospective analysis of the data of 532 patients who underwent AVR with implantation of the Mosaic Ultra prosthesis in the period 2007-2016 in our institution. Patients were classified according to their indexed effective orifice area (EOAi) to severe (EOAi < 0.65 cm2/m2), moderate (EOAi 0.65-0.85 cm2/m2), and absent/mild PPM (EOAi > 0.85 cm2/m2). In-hospital postoperative outcomes and the impact of PPM on mean transvalvular pressure gradient after stratification by prosthesis size were assessed. RESULTS: Overall, 3 (0.6%) patients had severe, 92 (17.3%) moderate, and 437 (82.1%) absent/mild PPM. There was a significant difference in PPM proportions (moderate/severe vs absent/mild PPM) across different prosthesis sizes overall (p < 0.0001), observing gradually increasing rates of PPM with decreasing prosthesis sizes. Patients with moderate/severe PPM had higher mean transvalvular pressure gradients (19 [13-25] vs 13 [10-17] mm Hg, p < 0.0001) than patients with absent/mild PPM. There was a significant difference in mean transvalvular pressure gradient between the different aortic valve prosthesis sizes overall (p < 0.0001), observing gradually increasing gradients with decreasing prosthesis sizes. CONCLUSION: Patients undergoing AVR with the smaller sized (19, 21, and 23 mm) Mosaic Ultra aortic valve prostheses exhibit a higher risk for moderate/severe PPM and higher mean aortic transvalvular pressure gradients than patients receiving the larger sized (25, 27, and 29 mm) prostheses.

Experience with a "hotline" service for outpatients on a ventricular assist device.

OBJECTIVES: With the growing number of outpatients on ventricular assist devices (VADs), there is an increasing need for "home discharge programs." One important feature is a 24-hour telephone service. In our center, the perfusionists run a so-called "hotline" for all of our VAD patients. This study analyzes the hotline calls with regard to frequency, the reason for calling, and the type of action undertaken. PATIENTS AND METHODS: Over a period of 5 years, 16 (12 EXCOR and 4 INCOR; Berlin Heart, Berlin, Germany) of 33 VAD patients (48%) were discharged and instructed to use the "hotline" service. All the calls received by the perfusionists were reviewed. We classified the calls into three levels according to the severity of the problem: Level (L) 1 = assistance provided by the perfusionist alone; L2 = calls requiring discussion with the surgeon on duty and/or visit to the outpatient clinic ahead of time; and L3 = immediate action and/or admission to the hospital. RESULTS: Over a period of 2,890 outpatient days (7.9 years), a total of 26 calls were registered. There were 0.9 calls per 100 patient days and 1.6 calls per discharged patient. Out of the 26 calls, 14 calls (54%) were classified as L1, 8 (31%) as L2, and 4 (15%) as L3. The most frequent reasons for L1 or L2 calls were fibrin deposits in the EXCOR pump chamber (39%), followed by battery dysfunction (19%). L3 calls were related to dysfunction of the EXCOR driving units in three cases and to an EXCOR pump chamber disconnection, which the patient did not survive. CONCLUSIONS: The institution of a hotline is an essential component of a VAD outpatient program. It provides a certain level of safety for the patient, although a residual risk remains.

Less invasive replacement of aortic root, ascending aorta and hemiarch via partial upper sternotomy: a propensity-score-matched comparison with full sternotomy.

OBJECTIVES: Less invasive surgery has emerged as an option for aortic pathologies. The current study compared our experience on early postoperative results of patients with aortic surgery between partial upper sternotomy (PUS) and full sternotomy (FS). METHODS: We performed a retrospective analysis of the data of patients undergoing aortic root surgery with concomitant ascending aorta and hemiarch replacement. Exclusion criteria were type A aortic dissection and other concomitant major cardiac surgery. After propensity score matching, we compared the perioperative outcomes of patients undergoing surgery with PUS versus FS. RESULTS: A total of 161 patients operated on between January 2013 and September 2022 met the inclusion criteria (PUS: n = 22, FS: n = 139). Propensity score matching yielded 22 pairs with a balanced distribution of propensity scores and covariates between the compared groups. There was no evidence that PUS affects cardiopulmonary bypass [108 (67-119) vs 113 (87-148) min, P = 0.154; PUS vs FS] and circulatory arrest duration [9 (7-10) vs 9 (8-13) min, P = 0.264; PUS vs FS]. There was a reduced cross-clamp duration in the PUS group [88 (58-96) vs 92 (71-122) min, P = 0.032]. Cumulative sum charts have shown consistently low cross-clamp and circulatory arrest duration for 2 experienced surgeons who performed 20 of the procedures in the PUS group (10 each). Perioperative mortality and morbidity were low, with no in-hospital mortality in the PUS group [0 vs 1(4.5%), P > 0.999] and absence of strokes in both groups. CONCLUSIONS: In summary, our initial experience suggests that less invasive aortic root, ascending aorta and hemiarch replacement via PUS could be performed in our patient cohort as safely as via full sternotomy. Advantages for the patient are reduced surgical trauma, improved cosmetic results and-presumably-less pain.

Navigating the challenges of minimally invasive mitral valve surgery: a risk analysis and learning curve evaluation.

BACKGROUND: This study aimed to report the risk and learning curve analysis of a minimally invasive mitral valve surgery program performed through a right mini-thoracotomy at a single institution. METHODS: From January 2013 through December 2019, 266 consecutive patients underwent minimally invasive mitral valve surgery in our department and were included in the current study. Multiple logistic regression analysis was used for the adverse event outcome. Distribution over time of perioperative complications, defined as clinical endpoints in the Valve Academic Research Consortium-2 (VARC-2) consensus document, as well as CUSUM charts for assessment of cardiopulmonary bypass and aortic cross-clamping duration over time, has been performed for learning curve assessment. RESULTS: Overall incidences of postoperative stroke (1.1%), myocardial infarction (1.1%), and thirty-day mortality (1.5%) were low. The mitral valve reconstruction rate in our series was 95%. Multivariable analysis revealed that concomitant tricuspid valve surgery (OR 4.44; 95%CI 1.61-11.80; p = 0.003) was significantly associated with adverse event outcomes. Despite a trend towards adverse event outcomes in patients with preexisting active mitral valve endocarditis (OR 2.69; 95%CI 0.81-7.87; p = 0.082), mitral valve pathology did not significantly impact postoperative morbidity and mortality. Distribution over time of perioperative complications, defined as clinical endpoints in the VARC-2 consensus document, showed a trend towards an improved complication rate after the initial 65-100 procedures. CONCLUSIONS: Mitral valve surgery via right-sided mini-thoracotomy can be implemented safely with low perioperative morbidity and mortality rates. Careful patient selection regarding isolated mitral valve surgery in the presence of degenerative mitral valve disease may represent a significant safety issue during the learning curve. TRIAL REGISTRATION: The cantonal ethics commission of Zurich approved the study (registration ID 2020-00752, date of approval 24 April 2020).

Generator pocket adhesions of cardiac leads: classification and correlation with transvenous lead extraction results.

OBJECTIVES: Pacemaker (PM) and implantable cardioverter defibrillator (ICD) leads become encapsulated intravascularly and in the generator pocket by fibrotic adhesions that accumulate over time. These adhesions are responsible for the difficulty and risk of lead extraction procedures. We developed a classification scheme for pocket adhesions, classified all of the patients in the cohort, and examined the relationship between pocket adhesions and the outcome of the procedure. METHODS: The classification of adhesions with respect to the intraoperative adhesion coverage was as followed: class 0 = adhesion free; class 1 ≤ 30% of adhesion coverage; class 2 = 30-60% of adhesion coverage; and class 3 ≥ 60% coverage. Patient data between December 2010 and March 2012 were collected. A total of 100 leads were extracted from 58 patients (1.7 ± 0.8 leads/patient); the mean lead implant duration was 78.5 ± 66.7 months, and the percentage of PM/ICD leads was 68% (n = 68)/32% (n = 32). RESULTS: Distribution of the leads among classes: 0 = 10; 1 = 17; 2 = 25; and 3 = 48. Average implant times (months) according to the adhesion classes: 0 = 1.2 ± 0.4; 1 = 19.8 ± 19.2; 2 = 79.3 ± 46.6; and 3 = 115.1 ± 106.0 (correlation-coefficient 0.71; P ≤ 0.05). Average numbers of extraction tools used according to the adhesions: 0 = none; 1 = 0.4 ± 0.7; 2 = 1.6 ± 1.0; and 3 = 2.3 ± 1.2 (correlation coefficient = 0.67; P ≤ 0.05). Complete removal was achieved in 100% of the patients in classes 0 and 1; 96% in class 2 (n = 24); and 75% in class 3 (n = 36) (P ≤ 0.05). Mortality = 0. CONCLUSIONS: Extensive adhesions in the generator pocket predict the need for a higher number of extraction tools. High-grade pocket adhesions predict lower success rates with regard to complete lead extraction. Both findings suggest that the degree of pocket adhesions predicts the degree of intravascular adhesions.

MicroRNA Mediated Cardioprotection - Is There a Path to Clinical Translation?

In the past 20 years, there have been several approaches to achieve cardioprotection or cardiac regeneration using a vast variety of cell therapies and remote ischemic pre-conditioning (RIPC). To date, substantial proof that either cell therapy or RIPC has the potential for clinically relevant cardiac repair or regeneration of cardiac tissue is still pending. Preclinical trials indicate that the secretome of cells in situ (during RIPC) as well as of transplanted cells may exhibit cardioprotective properties in the acute setting of cardiac injury. The secretome generally consists of cell-specific cytokines and extracellular vesicles (EVs) containing microRNAs (miRNAs). It is currently hypothesized that a subset of known miRNAs play a crucial part in the facilitation of cardioprotective effects. miRNAs are small non-coding RNA molecules that inhibit post-transcriptional translation of messenger RNAs (mRNAs) and play an important role in gene translation regulation. It is also known that one miRNAs usually targets multiple mRNAs. This makes predictability of pharmacokinetics and mechanism of action very difficult and could in part explain the inferior performance of various progenitor cells in clinical studies. Identification of miRNAs involved in cardioprotection and remodeling, the composition of miRNA profiles, and the exact mechanism of action are important to the design of future cell-based but also cell-free cardioprotective therapeutics. This review will give a description of miRNA with cardioprotective properties and a current overview on known mechanism of action and potential missing links. Additionally, we will give an outlook on the potential for clinical translation of miRNAs in the setting of myocardial infarction and heart failure.

Corrigendum to: Management of Tricuspid Regurgitation: The Role of Transcatheter Therapies.

[This corrects the article DOI: 10.15420/icr.2017:3:2.].

Management of Tricuspid Regurgitation: The Role of Transcatheter Therapies.

Surgical treatment is the gold standard treatment of functional tricuspid regurgitation (FTR) but this carries high risks of morbidity and mortality. Percutaneous procedures are an attractive alternative to surgery for selected patients deemed to be high-risk surgical candidates. A number of tricuspid transcatheter devices have been developed to treat FTR, but at present, evidence of their efficacy and safety is scarce. Preliminary data have shown promising results, but ongoing and future studies will provide a clearer picture of the benefits of these new techniques.

NAD+ protects against EAE by regulating CD4+ T-cell differentiation.

CD4(+) T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD(+)) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing immune homeostasis through CD4(+)IFNγ(+)IL-10(+) T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. We show that NAD(+) regulates CD4(+) T-cell differentiation through tryptophan hydroxylase-1 (Tph1), independently of well-established transcription factors. In the presence of NAD(+), the frequency of T-bet(-/-) CD4(+)IFNγ(+) T cells was twofold higher than wild-type CD4(+) T cells cultured in conventional T helper 1 polarizing conditions. Our findings unravel a new pathway orchestrating CD4(+) T-cell differentiation and demonstrate that NAD(+) may serve as a powerful therapeutic agent for the treatment of autoimmune and other diseases.

The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death.

The antibacterial amino-acid derivative taurolidine (TAU) has been recently shown to exhibit anti-neoplastic activity based on a mechanism, which is still unknown in detail. Cytotoxicity and clonogenic assays were performed and the impact of apoptosis modulators, a radical scavenger, autophagy inhibitors, silencing of apoptosis inducing actor (AIF) and cytochrome-c (Cyt-C) by siRNA, and knockdown of autophagy related genes were evaluated in vitro. The intracellular ATP-content, release of AIF and Cyt-C, and DNA-laddering were investigated. This study could demonstrate cell killing, inhibition of proliferation, and inhibition or prevention of colony formation in human glioma cell lines and ex vivo glioblastoma cells after incubation with TAU. This effect is based on the induction of a mixed type of programmed cell death with the main preference of autophagy, and involvement of senescence, necroptosis and necrosis. This mechanism of action may open a new approach for therapeutic intervention.