Exergaming in patients with a left ventricular assist device: a feasibility study.

AIMS: Exercise games (exergames) have been recently proposed as a mode of facilitating physical activity in patients with chronic diseases. Although patients supported with left ventricular assist devices (LVADs) benefit from physical activity, specific LVAD-related issues hinder their ability to exercise properly. The objective of this study was to assess the feasibility and safety of exergaming in LVAD-supported patients. METHODS AND RESULTS: Eleven LVAD-supported patients were enrolled in a 4 week exergaming programme using Nintendo Wii console with five sport games. Patients were instructed to play for 30 min a day, 5 days a week. Data on exercise capacity and exergaming were collected by using the 6 min walk test (6MWT) and a daily self-report diary, respectively. Feasibility of using the console and its safety was assessed by a semi-structured patient interview. Quality of life was assessed by the Minnesota Living with Heart failure Questionnaire (MLHFQ) and the Cantril's Ladder of Life. Safety was assessed by patient's report in interview and diary. The study group consisted of 10 male patients and 1 female patient, mean age of 67 ± 7 years, of whom 10 were supported with the HeartMate 3 LVAD for a median of 10 (interquartile range 3, 21) months. Baseline exercise capacity assessed by the 6MWT ranged from 240 to 570 m (mean 448 ± 112). After 4 weeks of exergaming, 6MWT distance increased from a mean of 448 ± 112 (evaluated in six patients) to 472 ± 113 m (P = 0.023). Patients' Cantril's Ladder of Life score improved numerically from an average of 6.13 to 7.67, as did their MLHFQ score from 45.9 ± 27 to 38.7 ± 18, with higher and lower scores, respectively, reflecting higher quality of life. No specific LVAD-related safety issues regarding exergaming were reported. CONCLUSIONS: Exergaming was found to be a safe and feasible mode for encouraging physical activity in LVAD-supported patients and carries a potential for improving exercise capacity and quality of life in these patients. Larger scale studies are warranted to further investigate the effect of exergaming in this patient population.

Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn).

BACKGROUND: Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls. METHODS: We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique. RESULTS: Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group. CONCLUSION: Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.

Combined mechanical circulatory support for ventricular fibrillation in left ventricular assist device patient.

Ventricular fibrillation, a life-threatening ventricular arrhythmia, may result in pulselessness, loss of consciousness and sudden cardiac death. In this case report, we describe our experience in managing a 54-year-old man with HeartMate3 left ventricular assist device (LVAD) as a bridge to transplantation due to dilated non-ischemic cardiomyopathy, presenting with incessant ventricular arrhythmia for 35 days despite multiple attempts to restore normal rhythm with external direct current cardioversion and anti-arrhythmic medications. The patient remained stable in ventricular arrhythmia with no progression to asystole, but hemodynamic collapse due to right heart failure occurred in the third week. Combined use of two mechanical circulatory support devices (LVAD with VA ECMO) was needed to achieve haemodynamic and metabolic stability, eventually leading to successful heart transplantation in the index admission. The patient was discharged home 2 weeks after transplantation in good clinical condition.

Metabolomic and microbiome profiling reveals personalized risk factors for coronary artery disease.

Complex diseases, such as coronary artery disease (CAD), are often multifactorial, caused by multiple underlying pathological mechanisms. Here, to study the multifactorial nature of CAD, we performed comprehensive clinical and multi-omic profiling, including serum metabolomics and gut microbiome data, for 199 patients with acute coronary syndrome (ACS) recruited from two major Israeli hospitals, and validated these results in a geographically distinct cohort. ACS patients had distinct serum metabolome and gut microbial signatures as compared with control individuals, and were depleted in a previously unknown bacterial species of the Clostridiaceae family. This bacterial species was associated with levels of multiple circulating metabolites in control individuals, several of which have previously been linked to an increased risk of CAD. Metabolic deviations in ACS patients were found to be person specific with respect to their potential genetic or environmental origin, and to correlate with clinical parameters and cardiovascular outcomes. Moreover, metabolic aberrations in ACS patients linked to microbiome and diet were also observed to a lesser extent in control individuals with metabolic impairment, suggesting the involvement of these aberrations in earlier dysmetabolic phases preceding clinically overt CAD. Finally, a metabolomics-based model of body mass index (BMI) trained on the non-ACS cohort predicted higher-than-actual BMI when applied to ACS patients, and the excess BMI predictions independently correlated with both diabetes mellitus (DM) and CAD severity, as defined by the number of vessels involved. These results highlight the utility of the serum metabolome in understanding the basis of risk-factor heterogeneity in CAD.

Six-months immunogenicity of BNT162b2 mRNA vaccine in heart transplanted and ventricle assist device-supported patients.

AIMS: To assess the 6 months immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplanted (HTx) recipients and left ventricular assist device (LVAD)-supported patients. METHODS AND RESULTS: A prospective single-centre cohort study of HTx recipients and LVAD-supported patients who received a two-dose SARSCoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech). Whole blood for anti-spike IgG (S-IgG) antibodies were drawn at 6 months after the first vaccine dose. S-IgG data at 6 weeks were available for a subgroup of HTx recipients. S-IgG ≥ 50 AU/mL were interpreted positive. The cohort included 53 HTx recipients and 18 LVAD-supported patients. The median time from HTx or LVAD implantation to the 1st vaccine dose was 90 (IQR 30, 172) months and 22 (IQR 6, 78) months, respectively. The seropositivity rates of S-IgG antibodies and their titre levels in HTx recipients and LVAD-supported patients were 45% and 83% respectively, (P = 0.006), and 35 (IQR 7, 306) AU/mL and 311 (IQR 86, 774) AU/mL, respectively, (P = 0.006). Reduced SARSCoV-2 vaccine immunogenicity in HTx recipients was associated with older age [odds ratio (OR) 0.917 confidence interval (CI 0.871, 0.966), P = 0.011] and with the use of anti-metabolites-based immunosuppressive regimens [OR 0.224 (CI 0.065, 0.777), P = 0.018]. mTOR inhibitors were associated with higher immunogenicity [OR 3.1 (CI 1.01, 9.65), P = 0.048]. Out of 13 HTx recipients who were S-IgG seropositive at 6 weeks after the first vaccine dose, 85% remained S-IgG seropositive at 6 month follow-up. CONCLUSIONS: At 6 months post-vaccination, S-IgG immunogenicity in HTx recipients is low, particularly in older HTx recipients and in those treated with anti-metabolites drugs.

Immunogenicity of the BNT162b2 mRNA vaccine in heart transplant recipients - a prospective cohort study.

AIMS: To assess the short-term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective single-centre cohort study of HTx recipients who received a two-dose SARS-CoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech). METHODS AND RESULTS: Whole blood for anti-spike IgG (S-IgG) antibodies was drawn at days 21-26 and at days 35-40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 [interquartile range (IQR) 44-69] years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6-14) years. Only 15% of HTx recipients demonstrated the presence of positive S-IgG antibody titres in response to the first vaccine dose [GMT 90 (IQR 54-229) AU/mL]. Overall, 49% of HTx recipients induced S-IgG antibodies in response to either the first or the full two-dose vaccine schedule [GMT 426 (IQR 106-884) AU/mL]. Older age [68 (IQR 59-70) years vs. 46 (IQR 34-63) years, P = 0.034] and anti-metabolite-based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non-responders to the first vaccine dose became S-IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S-IgG antibodies following SARS-CoV-2 two-dose vaccine. CONCLUSIONS: The generally achieved protection from SARS-CoV-2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.

Long-Term Outcomes of 560 Consecutive Patients Treated With Transcatheter Aortic Valve Implantation and Propensity Score-Matched Analysis of Early- Versus New-Generation Valves.

Transcatheter aortic valve implantation (TAVI) is an established treatment for severe aortic stenosis in patients at high or prohibitive surgical risk. Nevertheless, long-term clinical and echocardiographic data are still lacking. We carried out an analysis of 560 consecutive patients who underwent TAVI at our institution from 2008 to 2016 to evaluate temporal changes in TAVI characteristics, predictors of 1-year and long-term outcomes, and to compare the performance of the early- and new-generation valve systems. With time, we have adopted lower risk threshold for patient selection and have been using conscious sedation and transfemoral access preferentially (p <0.001 for all). The incidence of greater than mild PVL decreased from 16% to 7.6%, p = 0.029. Within 5 years, 47% of the patients died, the majority (78%) due to noncardiac causes. Independent predictors of 1-year death included periprocedural aspects (i.e., vascular complications, stroke, and PVL), whereas death occurring later than 1 year was solely related to baseline co-morbidities. Transvalvular gradients and residual regurgitation remained nonclinically significant for up to 5 years of follow-up. New-generation valves were associated with less PVL compared with propensity score-matched early-generation valves (p <0.001). In conclusion, TAVI utilization at our institution has progressed to include lower risk patients with transfemoral access becoming applicable in the great majority. Poor long-term survival is attributable to population factors rather than to procedural factors. Intermediate- and long-term hemodynamics are excellent. PVL has diminished significantly with the new-generation valves. Efforts to improve long- and short-term outcomes remain a therapeutic challenge.

Aortic Valve Gradient and Clinical Outcome in Patients Undergoing Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis.

OBJECTIVES: To explore the relation between the baseline aortic valve gradient (AVG) as a continuous variable and clinical outcomes following transcatheter aortic valve implantation (TAVI) in general and specifically in patients with high-gradient aortic stenosis (AS). METHODS: We reviewed 317 consecutive patients who underwent TAVI at our institution. We investigated the relation between AVG as a continuous/categorical variable and outcome among all patients and in patients without low-flow low-gradient AS, using the Cox proportional hazard model adjusting for multiple prognostic variables. RESULTS: Patients had a peak AVG of 79.9 ± 22.8 mm Hg (mean 50.5 ±15.7). During a mean follow-up of 2.7 years, AVG was inversely associated with mortality and mortality or cardiac hospitalization. Every 10-mm-Hg increase in peak AVG was associated with 18% reduction in mortality (p = 0.003) and 19% reduction in mortality/cardiac hospitalization (p < 0.001). Every 10-mm-Hg increase in mean AVG was associated with a 24% reduction in both outcomes (p = 0.005 and p < 0.001). Subgroup analysis of patients with left-ventricular ejection fraction >40% or peak AVG >64 mm Hg yielded similar results. CONCLUSIONS: Mean and peak baseline AVGs are directly associated with improved outcomes after TAVI; AVG can be used to select the patients most likely to benefit from TAVI.

Dynamic changes in left ventricular function after a percutaneous coronary intervention: prevalence, predictors, and prognosis.

OBJECTIVES: To estimate the prevalence, identify predictors, and assess the prognostic implications of left ventricular ejection fraction (LVEF) changes after an elective percutaneous coronary intervention (PCI). METHODS: We included all consecutive patients who underwent elective PCI in our institution and were evaluated with echocardiography before and within 1 year of the procedure. Patients were grouped in terms of baseline LVEF. Hazard ratios (HRs) for all-cause mortality and acute myocardial infarction were calculated for baseline LVEF groups and in terms of LVEF normalization or decline. RESULTS: A total of 974 patients were included. Patients with moderately impaired (HR 1.41, P=0.01) and poor LVEF (HR 2.44, P<0.001) had significantly worse survival in comparison with patients with good LVEF. Decline from preserved to impaired LVEF following PCI was associated with an increased 1-year risk (HR 3.48, P<0.001) and 5-year risk (HR 2.79, P<0.001) for the composite outcome of all-cause mortality and acute myocardial infarction. LVEF recovery from impaired to preserved was associated with a decreased 5-year risk for the composite outcome (HR 0.5, P<0.001). CONCLUSION: Changes in LVEF after elective PCI occur often. Both higher baseline LVEF and post-PCI LVEF normalization are associated with improved outcomes.

Type of Atrial Fibrillation and Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: There are limited data available regarding the relationship between atrial fibrillation (AF) clinical type, oral anticoagulation (OAC) treatment, and clinical outcome after transcatheter aortic valve replacement (TAVR). The study was designed to evaluate this relationship. METHODS: We analyzed data from the Rabin Medical Center TAVR registry, including 319 consecutive patients who underwent TAVR from 2008 to 2014. Patients were divided into three groups based on their history of AF: sinus rhythm (SR), paroxysmal AF (PAF), or nonparoxysmal AF (NPAF). RESULTS: There were 211 (66%), 56 (18%), and 52 (16%) patients in the SR, PAF, and NPAF groups, respectively. The cumulative risk for stroke or death at 2 years was highest among patients with NPAF (38%), but similarly low in PAF (15%) and SR patients (16%, P < 0.001). By multivariate analysis, patients with NPAF demonstrated a significantly higher risk of stroke or death (HR = 2.76, 95% CI 1.63-4.66, P < 0.001), as compared with SR. In contrast, patients with PAF had a similar risk of stroke or death compared with SR (HR = 0.80, P = 0.508). Patients with NPAF not treated with OAC demonstrated an 8.3-fold (P < 0.001) increased risk of stroke or death, whereas patients with PAF not treated with OAC had a similar risk of stroke or death compared with the SR group (HR = 1.25, P = 0.569). CONCLUSION: History of NPAF, but not PAF, is associated with a significant increased risk of stroke or death compared with sinus rhythm in patients undergoing TAVR.

Young patients with both type 1 diabetes mellitus and asthma have a unique IL-12 and IL-18 secretory pattern.

BACKGROUND: The expression of the regulatory cytokines interleukin (IL)-12 and IL-18 in patients with both Th1- and Th2-mediated diseases, type 1 diabetes mellitus (T1DM) and asthma, is unknown. OBJECTIVE: To investigate the in vivo and in vitro IL-12 and IL-18 secretion patterns in patients with both T1DM and asthma. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 44 patients. Mean age 19.4 ± 4.7 yr (10.5-28 yr), divided into four paired groups: T1DM and asthma, asthma only, T1DM only, and healthy controls. T-cell proliferative response was assessed. IL-12 and IL-18 serum levels and expression by PBMC following in vitro stimulation by lipopolysaccharide (LPS) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with T1DM and asthma had higher serum levels of both IL-12 and IL-18 compared to controls: 146.2 ± 69.2 and 109.7 ± 34.6 pg/mL, p = 0.038 and 436.1 ± 117.9, 320.2 ± 99.1 pg/mL, p = 0.028, respectively. Stimulated IL-12 secretion was significantly lower in these patients compared to those with one disease only: 809 ± 426.4, 2111.6 ± 2214.3, 3188.1 ± 2692.9 pg/mL and after 48 h: 956.3 ± 489.3, 2429.8 ± 2394.6, 3874.5 ± 2820.3 pg/mL, respectively, p < 0.03 for all. The IL-18/IL-12 serum ratio was also significantly higher in patients with both diseases compared to those with asthma only, p = 0.017. CONCLUSION: Patients with both T1DM and asthma display a different pattern of IL-12 and IL-18 expression compared to patients with one disease only and controls.