Tricuspid Valve Surgery in Patients Receiving Left Ventricular Assist Devices.

BACKGROUND: Tricuspid regurgitation (TR) is common and related to poor prognosis in patients after left ventricular assist device (LVAD) implantation. The concomitant tricuspid valve surgery (TVS) at the time of LVAD implantation on short and long-term outcomes are controversial in current evidence. METHODS: This is a single-center, observational, retrospective study. We enrolled patients with moderate-to-severe TR who received LVAD implantations from 2009 to 2020. Postoperative right ventricular failure (RVF), right ventricular assist device (RVAD) use, hospital mortality, new-onset renal replacement therapy (RRT), and acute kidney injury (AKI) were evaluated retrospectively. RESULTS: Sixty-eight patients were included, 36 with and 32 without concomitant TVS. Baseline characteristics did not differ between the two groups. Patients receiving TVS had significantly increased incidences of postoperative RVF (52.8 vs. 25.0%, p = 0.019), RVAD implantation (41.7 vs. 18.8%, p = 0.041), and new-onset RRT (22.2 vs. 0%, p = 0.004). No difference in the incidence of AKI and hospital mortality was detected. Besides, these associations remained consistent in patients who underwent LVAD implantation via median sternotomy. During a median follow-up of 2.76 years, Kaplan-Meier analysis and competing-risk analysis showed that TVS was not associated with better overall survival in patients after LVAD implantation compared with the no-TVS group. CONCLUSION: Our study suggests that concomitant TVS failed to show benefits in patients receiving LVAD implantation. Even worse, concomitant TVS is associated with significantly increased incidences of RVF, RVAD use, and new-onset of RRT. Considering the small sample size and short follow-up, these findings warrant further study.

Inpatient Cardiac Rehabilitation of LVAD Patients-Updated Recommendations from the Working Group of the German Society for Prevention and Rehabilitation of Cardiovascular Diseases.

Cardiac rehabilitation physicians are faced to an increasing number of heart failure patients supported by left ventricular assist devices (LVAD). Many of these patients have complex medical issues and prolonged hospitalizations and therefore need special cardiac rehabilitation strategies including psychological, social, and educational support which are actually poorly implemented.Cardiac rehabilitation with clear guidance and more evidence should be considered as an essential component of the patient care plan especially regarding the increasing number of destination patients and their long-term follow-up.In this article the working group for postimplant treatment and rehabilitation of LVAD patients of the German Society for Prevention and Rehabilitation of Cardiovascular Diseases has summarized and updated the recommendations for the cardiac rehabilitation of LVAD patients considering the latest literature.

Improved aftercare in LVAD patients: Development and feasibility of a smartphone application as a first step for telemonitoring.

For the success of the treatment with a left ventricular assist device (LVAD), both adequate self-management by the patient and an optimum level of support from the implanting hospital are crucial. A smartphone application has recently been developed within the framework of a European research project for the close monitoring of LVAD patients in order to improve upon their current aftercare situation. Using this new tool, different relevant parameters (eg, weight, international normalized ratio [INR], medication, LVAD parameters, symptoms, and photos of the driveline exit) can be sent daily or as required to a corresponding clinical application at the hospital for evaluation. The objective of this study was to monitor the functionality, acceptance, and usability of this smartphone application in LVAD patients. Prospective single-center study: in total, 13 patients (60 ± 7 years, 92% male, 1027 ± 653 days after LVAD implantation) were requested to test the application for approx. 4 weeks. At the end of the study, all entered data were evaluated and the patients were questioned regarding the acceptance and the usability. During the study period of mean 34 ± 8 days, a total of 453 data records (mean 35 ± 7 per patient) arrived at the hospital. In addition, a total of 19 photos of the driveline exit site were also sent via smartphone. The clinical application registered a total of 160 conspicuities. These comprised 126 INR deviations (target range 2.3-2.8) and 34 symptoms (mainly nosebleeds). The smartphone application functioned reliably, was well received by the patients and was graded highly for acceptance and usability. The results show that smartphone applications can definitely be used to improve aftercare in LVAD therapy in selected patients. Long-term studies are now needed to investigate the extent to which complications can be prevented, healthcare costs reduced, and quality of life increased.

Postoperative Complications and Long-Term Results after Primary Cardiac Sarcoma Resection.

BACKGROUND: Primary malignant cardiac tumors rarely occur in clinical care. Little is known about the impact of a parameter on postoperative survival. METHODS: From May 1991 to May 2014, a total of 24 patients underwent surgical treatment of a primary cardiac sarcoma in our center. We analyzed our clinical database retrospectively for information on patient characteristics and treatment data. The follow-up could be completed to 91.7%. RESULTS: Angiosarcoma and non-otherwise-specified sarcoma were the most common tumor entities. R0 resection was achieved in most cases. Postoperative mortality within the first 30 days was 20.8% (n = 5). In four of these five cases, postoperative low-output cardiac failure was the leading cause of death. The cumulative survival rate was 77.3% after 30 days, 68.2% after 3 months, 50.0% after 6 months, 45.0% after 12 months, and 18.0% after 24 months. The mean survival time in the whole group was 47.0 months. A low tumor differentiation was associated with low mean survival, but this was not statistically significant. Mean survival of sarcoma was higher after R0 resection. There was no significant rate of survival difference regarding the adjuvant therapy concept. CONCLUSION: Extended surgery alone or in combination with chemo- and/or radiotherapy may be successful in certain cases and may offer a satisfactory quality of life. The establishment of a multicenter heart tumor register in Germany is necessary to increase the number of cases in studies, get more remarkable study results, and standardize the diagnosis and therapy.

Metabolic volume performs better than SUVmax in the detection of left ventricular assist device driveline infection.

PURPOSE: A continuous-flow left ventricular assist device (LVAD) is a new and highly promising therapy in supporting end-stage heart failure patients, either bridging them to heart transplantation or as a destination therapy. Infection is one of the major complications associated with LVAD implants. 18F-FDG PET/CT has already been shown to be useful in the detection of LVAD infection. The goal of this study was to compare the diagnostic accuracy of different PET analysis techniques (visual grading versus SUVmax and metabolic volume). METHODS: We retrospectively analyzed 48 patients with implanted LVAD who underwent an 18F-FDG PET/CT that were either suspected to have a driveline or device infection or inflammation of unknown origin. PET/CT was analyzed qualitatively (visual grading) and quantitatively (SUVmax and metabolic volume) and matched to the final clinical diagnosis concerning driveline infection. The final diagnosis (standard of reference) was made at the end of clinically recorded follow-up or transplantation and included microbiological cultures of the driveline exit site and/or surgical samples, and clinical signs of infection despite negative cultures as well as recurrence of symptoms. RESULTS: Sensitivity, specificity, positive and negative predictive value were 87.5%, 79%, 81% and 86% for visual score, 87.5%, 87.5%, 87.5% and 87.5% for SUVmax and 96%, 87.5%, 88.5%, 95.5% for metabolic volume, respectively. ROC analysis revealed an AUC of .929 for SUVmax and .969 for metabolic volume. Both SUVmax and metabolic volume had a high detection rate of patients with driveline infection (21/24 = 91.5% true positive vs. 23/26 = 88.5% true positive, respectively). However, metabolic volume detected more patients without any infection correctly (1/22 = 4.5% false negative vs. 3/24 = 12.5% false negative). CONCLUSIONS: 18F-FDG PET/CT is a valuable tool for the diagnosis of LVAD driveline infection with high diagnostic accuracy. Particularly the use of the metabolic volume yields very high accuracy and performs slightly better than SUVmax.

[Quality of life and mental health of patients with severe heart failure with or without technical support for the left cardiac ventricle - a cross-sectional study]. / Lebensqualität und psychisches Befinden von Patienten mit schwerer Herzinsuffizienz mit und ohne apparative Unterstützung der Funktion des linken Ventrikels ­ eine Querschnittsstudie.

Quality of life and mental health of patients with severe heart failure with or without technical support for the left cardiac ventricle - a cross-sectional study Objectives: Chronic heart failure is associated with reduced quality of life (QoL) and poor prognosis. Support via a left ventricular assist device (LVAD) is an alternative to optimised medical management for patients with advanced heart failure. This study evaluated health-related QoL with both therapy options. METHODS: In this consecutive cross-sectional study, patients with LVAD support (n = 50) and patients with optimised medical management (n = 50) were interviewed comprehensively about various domains of QoL, emotional stress, perceived self-efficacy, social support, life satisfaction, and communication. RESULTS: LVAD patients had a better overall QoL (KCCQ, clinical summary: MW: 67.4 vs. 52.9). Patients with medical management reported increased emotional stress stemming from depressed mood (HADS-D, MW: 7.1 vs.MW: 6.0). Depressed mood proved to be the most significant negative predictor for health-related QoL as well as for emotional well-being. CONCLUSIONS: Although they had a worse clinical situation preoperatively, LVAD patients had a significantly better QoL in both physical dimensions and functional competencies as well as significantly less psychological stress through depressed mood and anxiety.

Left Ventricular Assist Devices as Bridge to Cardiac Recovery in Nonischemic Heart Failure: Keeping Weaning from the Device in Mind.

A minority of patients on left ventricular assist devices (LVADs) display myocardial recovery raising the question of device explantation. We report a series of seven LVAD patients with nonischemic cardiomyopathy allowing explantation of the VAD. In case of four patients we overview follow-up periods of 4 to 10 years. Remarkably, in three cases device explantation was considered beyond 1 year of LVAD support. Explantation was finally performed after 20 months and more on the device. In light of the scarcity of donor organs we conclude that patients on LVAD support should be evaluated for possible weaning from the device on a regular basis.

Pulmonary Bleeding During Right Ventricular Support After Left Ventricular Assist Device Implantation.

OBJECTIVES: Right heart failure still occurs in up to 20% of patients after implantation of a left ventricular assist device (LVAD). One treatment option for these patients is the implantation of a temporary right ventricular assist device (RVAD). Experimental data suggest that non-pulsatile perfusion of the lungs is associated with an increased rate of pulmonary hemorrhage. The aim of this study was to determine the incidence of pulmonary bleeding complications in these patients. DESIGN: Observational study. SETTING: Single center, university hospital. PARTICIPANTS: This study included patients undergoing LVAD implantation for end-stage heart failure and subsequent implantation of a temporary right ventricular support system. INTERVENTIONS: In this study, 25 patients who underwent LVAD and additional temporary RVAD implantation were screened for pulmonary bleeding complications. MEASUREMENTS AND MAIN RESULTS: The mean Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level at the time of LVAD implantation was 2.84. All patients experienced severe right ventricular failure (tricuspid annular plane systolic excursion [TAPSE], 10.16±26.3 mm) and severe pulmonary hypertension (right atrial [RA] pressure, 56.21±15.58 mmHg). Average duration of right ventricular support was 11.12±7.20 days, with right ventricular support being administered to 14 patients for more than 7 days. Seventeen patients were weaned successfully from right ventricular support after a mean support duration of 5 days. Five patients developed pulmonary bleeding complications, diagnosed using computed tomography scan and bronchoscopy. All bleeding occurred after postoperative day 7 and was associated with RVAD flow of more than 4 L/min within 24 hours before bleeding occurred. CONCLUSIONS: The data presented in this study suggested that right ventricular support for more than 7 days and a blood flow greater than 4 L/min were associated with pulmonary bleeding complications. This should be taken into consideration when temporary right ventricular support after LVAD implantation is planned.

Can Perioperative Right Ventricular Support Prevent Postoperative Right Heart Failure in Patients With Biventricular Dysfunction Undergoing Left Ventricular Assist Device Implantation?

OBJECTIVES: Depending on the pre-existing condition of the right ventricle (RV), left ventricular assist device (LVAD) implantation may have a detrimental effect on RV function, subsequently leading to right heart failure. This study details the authors' experience with perioperative mechanical RV support in patients with biventricular impairment but primarily scheduled for isolated LVAD implantation. DESIGN: Retrospective study. SETTING: Two center study, university hospital. PARTICIPANTS: This study included LVAD recipients with preoperative biventricular impairment who received an additional right ventricular assist device (RVAD) after a failed weaning attempt from cardiopulmonary bypass due to acute RV failure. INTERVENTIONS: Outcomes of 25 patients who underwent LVAD and unplanned temporary RVAD implantation were analyzed. MEASUREMENTS AND MAIN RESULTS: All patients experienced significant preoperative RV impairment (tricuspid annular plane systolic excursion: 10.2±26.3 mm; right atrium pressure: 17.9±10.4 mmHg) and pulmonary hypertension (pulmonary artery pressure: 54.8±25.7 mmHg). In 15 patients, additional tricuspid valve annuloplasty was performed. Mean duration of temporary RVAD support was 11.1±7.2 days. In 23 patients (92%), the RVAD was removed successfully. None of the patients developed RV failure after RVAD removal. Hospital survival and the 1-year survival rate of the study group were 68% and 56%, respectively. CONCLUSIONS: The results of perioperative RVAD support in LVAD recipients with biventricular dysfunction are encouraging. Temporary RVAD support allows an already compromised RV to become attuned to the hemodynamic conditions after LVAD implantation. This strategy provides patients with preoperative impaired RV function a high likelihood to permanently undergo LVAD support only.

Is Implantation of a Left Ventricular Assist Device in Patients With Critical or Impending Cardiogenic Shock an Absolute Contraindication? Looking Back at Our Past Experience Trying to Identify Contraindicative Risk Factors.

Poor survival has been demonstrated after ventricular assist device (VAD) implantation for Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 and 2 patients compared with more stable levels. However, risk factors within this high-risk cohort have not been determined so far. The aim of the present study was to identify risk factors associated with this very high mortality rate. Between February 1993 and January 2013, 298 patients underwent VAD implantation in our institution. One hundred nine patients were in INTERMACS level 1 and 49 patients were in INTERMACS level 2 and were therefore defined as hemodynamically critical (overall 158 patients). Assist devices implanted were: HVAD HeartWare n = 18; Incor n = 11; VentrAssist n = 2; DeBakey n = 22; and pulsatile systems n = 105. After cumulative support duration of 815.35 months, Kaplan-Meier analysis revealed a survival of 63.9, 48.8, and 40.3% at 1, 6, and 12 months, respectively. Cox regression analyses identified age > 50 (P = 0.001, odds ratio [OR] 2.48), white blood cell count > 13.000/µL (P = 0.01, OR 2.06), preoperative renal replacement therapy (P = 0.001, OR 2.63), and postcardiotomy failure (P < 0.001, OR 2.79) as independent predictors of mortality. Of note, last generation VADs were not associated with significantly better 6-month survival (P = 0.59). Patients without the aforementioned risk factors could yield a survival of 79.2% at 6 months. This single-center experience shows that VAD implantation in hemodynamically unstable patients generally results in poor early outcome, even in third-generation pumps. However, avoiding the aforementioned risk factors could result in improved outcome.

Survival results after implantation of intrapericardial third-generation centrifugal assist device: an INTERMACS-matched comparison analysis.

Reports on third-generation centrifugal intrapericardial pumps (HeartWare International, Inc., Framingham, MA, USA) have shown better survival results than the previous-generation devices. However, outcomes depending on the preoperative level of stability can substantially differ, resulting in a limited analysis of potentialities and drawbacks of a given device. In the present study we sought to compare in our single-center experience the survival results of this third-generation device with previous left ventricular systems taking into account the different preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels. Between February 1993 and March 2012, 287 patients underwent assist device implantation in our university hospital (INTERMACS Level 1-2 = 158 patients; INTERMACS Level 3-4-5 = 129 patients). Assist devices implanted were: Group A (HVAD HeartWare, n = 52), group B (previous continuous-flow ventricular assist device [VAD], InCor [Berlin Heart, Berlin, Germany], n = 37; VentrAssist [VentraCor, Inc., Chatswood, NSW, Australia], n = 7; DeBakey [MicroMed Cardiovascular, Inc., Houston, TX, USA], n = 32), and group C (pulsatile systems, n = 159). After cumulative support duration of 54 436 days and a mean follow-up of 6.21 ± 7.46 months (range 0-45.21 months), log-rank analysis revealed a survival for group A of 82.0%, 70.4%, and 70.4%; for group B of 84.0%, 48.2%, 33.7%; and for group C of 71.6%, 46.1%, 33.8%, at 1, 12, and 24 months respectively, with a significantly (P = 0.013) better outcome for group A. When stratifying the survival on the basis of INTERMACS level, no significant survival improvement was observed among all patients who underwent VAD implantation in INTERMACS 1-2 (P = 0.47). However, among patients who underwent elective VAD implantation (INTERMACS 3-4-5), group A had a significantly better outcome (P = 0.005) compared with the other INTERMACS-matched groups (B,C) with a survival rate of 88.8% in group A versus 34.2% in group B and 45.6% in group C at 24 months, respectively. Elective HVAD system implantation shows improved survival benefit over the other INTERMACS-matched devices. Moreover, preoperative unstable hemodynamics resulted in a poor prognosis independently from the pump generation.

Economic aspects of long-term left ventricular assist device treatment for chronic heart failure.

AIMS: Technological advances and the current shortage of donor organs have contributed to an increase in the number of left ventricular assist device (LVAD) implantations in patients with end-stage heart failure. Demographic change and medical progress might raise the number of these patients, resulting in a further increase in the number of LVAD implantations. The aim of this study was to evaluate the long-term costs of LVAD therapy and identify diagnoses resulting in expensive stays. METHODS AND RESULTS: In this retrospective analysis of prospectively collected data, all patients after implantation of a second- or third-generation LVAD by 31 March 2022 were included. In addition to demographic and survival data, revenues and case mix points were determined for each patient. Of the 163 patients included, 75.5% were male. The mean age at LVAD implantation was 52 ± 14 years. The mean survival was 1458 ± 127 days. During follow-up, the total inpatient treatment time per patient was 70 ± 87 days. The average duration of outpatient treatment was 55.1%, based on the total duration of support. The average revenue per patient for the implant stay was $193 192.35 ± $111 801.29, for inpatient readmissions $52 068.96 ± $116 630.00, and for outpatient care $53 195.94 ± $62 363.53. CONCLUSIONS: LVAD implantation in patients with end-stage heart failure leads to improved survival but a significant increase in treatment costs. Further multi-centre studies are necessary in order to be able to assess the effects of long-term LVAD treatment on the healthcare system.

BMI-Stratified Exploration of the 'Obesity Paradox': Heart Failure Perspectives from a Large German Insurance Database.

Background: The global rise of obesity and its association with cardiovascular risk factors (CVRF) have highlighted its connection to chronic heart failure (CHF). Paradoxically, obese CHF patients often experience better outcomes, a phenomenon known as the 'obesity paradox'. This study evaluated the 'obesity paradox' within a large cohort in Germany and explored how varying degrees of obesity affect HF outcome. Methods: Anonymized health claims data from the largest German insurer (AOK) for the years 2014-2015 were utilized to analyze 88,247 patients hospitalized for myocardial infarction. This analysis encompassed baseline characteristics, comorbidities, interventions, complications, and long-term outcomes, including overall survival, freedom from CHF, and CHF-related rehospitalization. Patients were categorized based on body mass index. Results: Obese patients encompassed 21.3% of our cohort (median age 68.69 years); they exhibited a higher prevalence of CVRF (p < 0.001) and comorbidities than non-obese patients (median age 70.69 years). Short-term outcomes revealed lower complication rates and mortality (p < 0.001) in obese compared to non-obese patients. Kaplan-Meier estimations for long-term analysis illustrated increased incidences of CHF and rehospitalization rates among the obese, yet with lower overall mortality. Multivariable Cox regression analysis indicated that obese individuals faced a higher risk of developing CHF and being rehospitalized due to CHF but demonstrated better overall survival for those classified as having low-level obesity (p < 0.001). Conclusions: This study underscores favorable short-term outcomes among obese individuals. The 'obesity paradox' was confirmed, with more frequent CHF cases and rehospitalizations in the long term, alongside better overall survival for certain degrees of obesity.

Calcium channel blockers and clinical outcomes in patients with continuous-flow left ventricular assist devices.

AIMS: Current guidelines suggest calcium channel blockers (CCBs) as the second or third option for blood pressure management in patients with left ventricular assist device (LVAD). However, the clinical outcomes of patients with LVAD who receive CCBs remain unclear. Our study aims to analyse the association of CCBs with clinical outcomes in patients after LVAD implantation. METHODS AND RESULTS: This is a retrospective analysis based on the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017, and adult patients who were alive with LVAD and CCB treatment information at 6 months after implantation were included. Among 10 717 patients, 1369 received CCBs 6 months after implantation, and there was an increasing trend of CCB use after LVAD. Patients receiving CCB therapy at 6 months had a similar 5 year survival rate to those not receiving CCB [49.6%, 95% confidence interval (CI): 47.5-51.7% vs. 51.1%, 95% CI: 45.3-56.7%]. In both Cox and competing risk regressions after adjusting for confounding factors, CCB treatment at 6 months after implantation was not associated with long-term mortality [hazard ratio (HR): 1.03, 95% CI: 0.91-1.17, P = 0.624 and subdistribution HR (SHR): 1.07, 95% CI: 0.95-1.22, P = 0.260]. Consistently, in time-varying models, CCB treatment was not linked to long-term mortality (HR: 0.97, 95% CI: 0.87-1.09, P = 0.682 and SHR: 1.05, 95% CI: 0.94-1.18, P = 0.359). This null association remained in subgroup analysis according to device strategy and propensity-matching analyses. Neurological dysfunction, stroke, bleeding, rehospitalization, and renal dysfunction were more likely to occur among those with CCB when compared with those without CCB treatment. CONCLUSIONS: In patients with LVAD, CCB therapy fails to show benefits in long-term survival and is associated with increased incidences of neurological dysfunction, bleeding, renal dysfunction, and rehospitalization.

Impact of enzyme replacement therapy and migalastat on left atrial strain and cardiomyopathy in patients with Fabry disease.

Aims: Cardiomyopathy in Fabry disease (FD) is a major determinant of morbidity and mortality. This study investigates the effects of FD-specific treatment using enzyme replacement therapy (ERT) and chaperone therapy on left atrial (LA) function using two-dimensional speckle tracking echocardiography (2DSTE). Methods and results: In this prospective observational single-center study, 20 FD patients [10 (50%) females] treated with migalastat, 48 FD patients [24 (50%) females] treated with ERT (agalsidase-alfa and agalsidase-beta), and 30 untreated FD patients (all females) as controls were analyzed. The mean follow-up time ranged from 26 to 81 months. 2DSTE was performed for left ventricle strain, right ventricle strain, and LA strain (LAS). FD-specific treated patients presented with increased left ventricular mass index (LVMi) and higher frequency of left ventricular hypertrophy at baseline, whereas untreated control patients showed normal baseline values. FD-specific treated (including migalastat and ERT) patients showed stabilization of LAS over time (p > 0.05). LVMi was also stable in treated FD patients during observation (p > 0.05). Conclusion: In patients with FD, treated with either ERT or chaperone therapy, LAS values measured by echocardiographic speckle tracking were stable over time, pointing toward disease stabilization.

Hemodynamic markers of pulmonary vasculopathy for prediction of early right heart failure and mortality after heart transplantation.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) is broadly accepted as an imminent risk factor for mortality after heart transplantation (HTx). However, no current HTx recipient risk score includes PVR or other hemodynamic parameters. This study examined the utility of various hemodynamic parameters for risk stratification in a contemporary HTx population. METHODS: Patients from seven German HTx centers undergoing HTx between 2011 and 2015 were included retrospectively. Established risk factors and complete hemodynamic datasets before HTx were analyzed. Outcome measures were overall all-cause mortality, 12-month mortality, and right heart failure (RHF) after HTx. RESULTS: The final analysis included 333 patients (28% female) with a median age of 54 (IQR 46-60) years. The median mean pulmonary artery pressure was 30 (IQR 23-38) mm Hg, transpulmonary gradient 8 (IQR 5-10) mm Hg, and PVR 2.1 (IQR 1.5-2.9) Wood units. Overall mortality was 35.7%, 12-month mortality was 23.7%, and the incidence of early RHF was 22.8%, which was significantly associated with overall mortality (log-rank HR 4.11, 95% CI 2.47-6.84; log-rank p < .0001). Pulmonary arterial elastance (Ea) was associated with overall mortality (HR 1.74, 95% CI 1.25-2.30; p < .001) independent of other non-hemodynamic risk factors. Ea values below a calculated cutoff represented a significantly reduced mortality risk (HR 0.38, 95% CI 0.19-0.76; p < .0001). PVR with the established cutoff of 3.0 WU was not significant. Ea was also significantly associated with 12-month mortality and RHF. CONCLUSIONS: Ea showed a strong impact on post-transplant mortality and RHF and should become part of the routine hemodynamic evaluation in HTx candidates.

Efficacy and safety of sacubitril/valsartan in an outpatient setting: A single-center real-world retrospective study in HFrEF patients with focus on possible predictors of clinical outcome.

BACKGROUND: Currently, data on sacubitril/valsartan therapy from the real-world settings are scarce and the predictors of a good clinical responsiveness to this drug are unknown. OBJECTIVES: To assess efficacy and safety profile of sacubitril/valsartan and to identify predictors for a better clinical outcome. MATERIAL AND METHODS: Clinical, laboratory and echocardiographic data of 95 chronic heart failure (CHF) patients with reduced ejection fraction (HFrEF) were retrospectively analyzed. A good efficacy of sacubitril/valsartan was defined as the fulfilment of at least 2 of the following criteria: improvement of left ventricular ejection fraction (LVEF) or functional status, and reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels or hospitalization rates. RESULTS: Under sacubitril/valsartan, major improvements were observed in LVEF, the New York Heart Association (NYHA) class, NT-proBNP levels, and hospitalization rates. Patients with a good efficacy of sacubitril/valsartan were characterized by initially worse LVEF (median (interquartile range (IQR)): 29.0% (23.0-33.0%) compared to 32.0% (28.5-38.0%) with more frequent nonischemic etiology (65.4% compared to 41.9%) and hospitalizations for CHF/month (0.016 (0.004-0.057) compared to 0.000 (0.000-0.012)), lower cholesterol (42.3% compared to 65.1%), higher C-reactive protein (CRP) levels at baseline (0.5 mg/L (0.5-1.0 mg/L) compared to 0.5 mg/L (0.5-0.5 mg/L)), and a shorter timespan between CHF diagnosis and the start of sacubitril/valsartan treatment (66.0 (11.0-127.0) compared to 111 (73.0-211.0) months) (p < 0.05 each). In a multivariate Cox analysis, only the last 2 parameters were shown to be independent predictors of good clinical responsiveness to sacubitril/valsartan (hazard ratio (HR) = 1.263, 95% confidence interval (95% CI) = [1.048; 1.521]; HR = 0.992, 95% CI = [0.987; 0.997], p < 0.05, respectively). CONCLUSIONS: Sacubitril/valsartan improved LVEF, NYHA class, NT-proBNP levels, and hospitalization rates, mostly without relevant side effects. The independent predictors of a good clinical efficacy were higher CRP levels at baseline and a shorter delay between CHF diagnosis and the initialization of sacubitril/valsartan therapy.

An external validation study of the Utah Bleeding Risk Score.

OBJECTIVES: Gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices (CF-LVAD) impairs quality of life and increases hospitalization rate. The Utah Bleeding Risk Score (UBRS) has been created to predict gastrointestinal bleeding (GIB) in patients on left ventricular assist device. We here aimed to externally validate UBRS on our cohort of CF-LVAD patients. METHODS: Utah Bleeding Risk Score was calculated, GIB events summarized on follow-up and patients stratified into 3 risk groups. Predictive ability of UBRS was examined at 3 years and during whole support time and person time incidence rates correlated to UBRS. In a sub-analysis, single effects of UBRS variables on freedom from GIB were assessed. RESULTS: A total of 111 CF-LVAD patients were included. The median UBRS was 2 (3-1). Receiver operating characteristic curve analysis showed an area under the curve of 0.519 (P = 0.758, 95% confidence interval = 0.422-0.615) at 3 years and an area under the curve of 0.515 (P = 0.797, 95% confidence interval = 0.418-0.611) during whole support time. No significant difference was observed in UBRS between bleeders and non-bleeders (P = 0.80). No significant difference in freedom from GIB was observed (P3 years = 0.7; Psupport-time = 0.816) and no independent significance regarding the freedom from bleeding at 3 years for any variable was observed. Coronary artery disease was associated with higher risk of GIB beyond the 3rd year (P = 0.048). CONCLUSIONS: UBRS was not able to predict GIB and therefore not applicable in our cohort of patients. Coronary artery disease could lead to a higher risk for GIB during support time. An additional validation in a larger cohort is advisable.

C-reactive protein predicts early clinical outcomes and long-term mortality after left ventricular assisted device.

OBJECTIVES: Left ventricular assist device (LVAD) implantation has become a reliable therapeutic strategy in patients with advanced heart failure. C-reactive protein (CRP) is a well-established biomarker of inflammation. This study aims to determine the prognostic effect of CRP level on clinical outcomes of patients who undergo LVAD implantation. METHODS: This is a single-center, observational, retrospective study. One hundred fifty-three patients who received continuous-flow LVAD implantation were included and were divided into two groups of high (>3.9 mg/dL) versus low CRP (⩽3.9 mg/dL). RESULTS: Patients with high pre-implant CRP levels were prone to severe preoperative clinical conditions and complicated intraoperative procedures. Compared with patients in the low CRP group, elevated pre-implant CRP was associated with increased hospital mortality (31.4% vs 8.4%, p < 0.001), postoperative right ventricular failure (47.1% vs 30.1%, p = 0.031), right ventricular assist device use (34.3% vs 16.9%, p = 0.013), AKI (70% vs 51.8%, p = 0.022) and significantly prolonged duration of postoperative mechanical ventilation and intensive care unit length of stay. Univariate Cox regression showed that high pre-implant CRP was significantly associated with increased risk of long-term mortality (Hazard ratio (HR) 2.632 95%; CI: 1.657-4.183, p < 0.001), and multivariable Cox regression also revealed the higher risk of long-term mortality in patients with elevated pre-implant CRP (HR, 2.848 95%CI: 1.659-4.888, p < 0.001). These results remained stable when treating pre-implant CRP as a continuous variable. Besides, the prognostic effect of post-implant CRP was also observed. CONCLUSIONS: CRP is a reliable risk-stratification biomarker in patients receiving continuous-flow -LVAD and can be used as a predictor for short- and long-term outcomes.

Protein phosphatase 2A affects myofilament contractility in non-failing but not in failing human myocardium.

Protein phosphatase (PP) type 2A is a multifunctional serine/threonine phosphatase that is involved in cardiac excitation-contraction coupling. The PP2A core enzyme is a dimer, consisting of a catalytic C and a scaffolding A subunit, which is targeted to several cardiac proteins by a regulatory B subunit. At present, it is controversial whether PP2A and its subunits play a critical role in end-stage human heart failure. Here we report that the application of purified PP2AC significantly increased the Ca2+-sensitivity (ΔpCa50=0.05±0.01) of the contractile apparatus in isolated skinned myocytes of non-failing (NF) hearts. A higher phosphorylation of troponin I (cTnI) was found at protein kinase A sites (Ser23/24) in NF compared to failing myocardium. The basal Ca2+-responsiveness of myofilaments was enhanced in myocytes of ischemic (ICM, ΔpCa50=0.10±0.03) and dilated (DCM, ΔpCa50=0.06±0.04) cardiomyopathy compared to NF. However, in contrast to NF myocytes the treatment with PP2AC did not shift force-pCa relationships in failing myocytes. The higher basal Ca2+-sensitivity in failing myocytes coincided with a reduced protein expression of PP2AC in left ventricular tissue from patients suffering from ICM and DCM (by 50 and 56% compared to NF, respectively). However, PP2A activity was unchanged in failing hearts despite an increase of both total PP and PP1 activity. The expression of PP2AB56α was also decreased by 51 and 62% in ICM and DCM compared to NF, respectively. The phosphorylation of cTnI at Ser23/24 was reduced by 66 and 49% in ICM and DCM compared to NF hearts, respectively. Our results demonstrate that PP2A increases myofilament Ca2+-sensitivity in NF human hearts, most likely via cTnI dephosphorylation. This effect is not present in failing hearts, probably due to the lower baseline cTnI phosphorylation in failing compared to non-failing hearts.