Transcatheter and surgical aortic valve replacement in patients with bicuspid aortic valve

Objectives: To compare the outcomes after surgical (SAVR) and transcatheter aortic valve replacement (TAVR) for severe stenosis of bicuspid aortic valve (BAV).Methods: We evaluated the early and mid-term outcome of patients with stenotic BAV who underwent SAVR or TAVR for aortic stenosis from the nationwide FinnValve registry.Results: The FinnValve registry included 6463 AS patients and 1023 (15.8%) of them had BAV. SAVR was performed in 920 patients and TAVR in 103 patients with BAV. In the overall series, device success after TAVR was comparable to SAVR (94.2% vs. 97.1%, p = 0.115). TAVR was associated with increased rate of mild-to-severe paravalvular regurgitation (PVR) (19.4% vs. 7.9%, p < 0.0001) and of moderate-to-severe PVR (2.9% vs. 0.7%, p = 0.053). When newer-generation TAVR devices were evaluated, mild-to-severe PVR (11.9% vs. 7.9%, p = 0.223) and moderate-to-severe PVR (0% vs. 0.7%, p = 1.000) were comparable to SAVR. Type 1 N-L and type 2 L-R/R-N were the BAV morphologies with higher incidence of mild-to-severe PVR (37.5% and 100%, adjusted for new-generation prostheses p = 0.025) compared to other types of BAVs. Among 75 propensity score-matched cohorts, 30-day mortality was 1.3% after TAVR and 5.3% after SAVR (p = 0.375), and 2-year mortality was 9.7% after TAVR and 18.7% after SAVR (p = 0.268) CONCLUSIONS: In patients with stenotic BAV, TAVR seems to achieve early and mid-term results comparable to SAVR. Type 1 N-L and type 2 L-R/R-N BAV morphologies had higher incidence of PVR. Larger studies evaluating different phenotypes of BAV are needed to confirm these findings.</p

Comparison of Outcomes After Transcatheter Aortic Valve Replacement vs Surgical Aortic Valve Replacement Among Patients With Aortic Stenosis at Low Operative Risk

Importance:  Transcatheter aortic valve replacement (TAVR) has been shown to be a valid alternative to surgical aortic valve replacement (SAVR) in patients at high operative risk with severe aortic stenosis (AS). However, the evidence of the benefits and harms of TAVR in patients at low operative risk is still scarce.Objective:  To compare the short-term and midterm outcomes after TAVR and SAVR in low-risk patients with AS.Design, Setting, and Participants:  This retrospective comparative effectiveness cohort study used data from the Nationwide Finnish Registry of Transcatheter and Surgical Aortic Valve Replacement for Aortic Valve Stenosis of patients at low operative risk who underwent TAVR or SAVR with a bioprosthesis for severe AS from January 1, 2008, to November 30, 2017. Low operative risk was defined as a Society of Thoracic Surgeons Predicted Risk of Mortality score less than 3% without other comorbidities of clinical relevance. One-to-one propensity score matching was performed to adjust for baseline covariates between the TAVR and SAVR cohorts.Exposures:  Primary TAVR or SAVR with a bioprosthesis for AS with or without associated coronary revascularization.Main Outcomes and Measures:  The primary outcomes were 30-day and 3-year survival.Results:  Overall, 2841 patients (mean [SD] age, 74.0 [6.2] years; 1560 [54.9%] men) fulfilled the inclusion criteria and were included in the analysis; TAVR was performed in 325 patients and SAVR in 2516 patients. Propensity score matching produced 304 pairs with similar baseline characteristics. Third-generation devices were used in 263 patients (86.5%) who underwent TAVR. Among these matched pairs, 30-day mortality was 1.3% after TAVR and 3.6% after SAVR (P = .12). Three-year survival was similar in the study cohorts (TAVR, 85.7%; SAVR, 87.7%; P = .45). Interaction tests found no differences in terms of 3-year survival between the study cohorts in patients younger than vs older than 80 years or in patients who received recent aortic valve prostheses vs those who did not.Conclusions and Relevance:  Transcatheter aortic valve replacement using mostly third-generation devices achieved similar short- and mid-term survival compared with SAVR in low-risk patients. Further studies are needed to assess the long-term durability of TAVR prostheses before extending their use to low-risk patients.</p

Cardiac Function, Perfusion, Metabolism, and Innervation following Autologous Stem Cell Therapy for Acute ST-Elevation Myocardial Infarction. A FINCELL-INSIGHT Sub-Study with PET and MRI

Purpose: Beneficial mechanisms of bone marrow cell (BMC) therapy for acute ST-segment elevation myocardial infarct (STEMI) are largely unknown in humans. Therefore, we evaluated the feasibility of serial positron emission tomography (PET) and MRI studies to provide insight into the effects of BMCs on the healing process of ischemic myocardial damage. Methods: Nineteen patients with successful primary reteplase thrombolysis (mean 2.4 h after symptoms) for STEMI were randomized for BMC therapy (2.9 × 106 CD34+ cells) or placebo after bone marrow aspiration in a double-blind, multi-center study. Three days post-MI, coronary angioplasty, and paclitaxel eluting stent implantation preceded either BMC or placebo therapy. Cardiac PET and MRI studies were performed 7–12 days after therapies and repeated after 6 months, and images were analyzed at a central core laboratory. Results: In BMC-treated patients, there was a decrease in [11C]-HED defect size (−4.9 ± 4.0 vs. −1.6 ± 2.2%, p = 0.08) and an increase in [18F]-FDG uptake in the infarct area at risk (0.06 ± 0.09 vs. −0.05 ± 0.16, p = 0.07) compared to controls, as well as less left ventricular dilatation (−4.4 ± 13.3 vs. 8.0 ± 16.7 mL/m2, p = 0.12) at 6 months follow-up. However, BMC treatment was inferior to placebo in terms of changes in rest perfusion in the area at risk (−0.09 ± 0.17 vs. 0.10 ± 0.17, p = 0.03) and infarct size (0.4 ± 4.2 vs. −5.1 ± 5.9 g, p = 0.047), and no effect was observed on ejection fraction (p = 0.37). Conclusion: After the acute phase of STEMI, BMC therapy showed only minor trends of long-term benefit in patients with rapid successful thrombolysis. There was a trend of more decrease in innervation defect size and enhanced glucose metabolism in the infarct-related myocardium and also a trend of less ventricular dilatation in the BMC-treated group compared to placebo. However, no consistently better outcome was observed in the BMC-treated group compared to placebo

Blood Transfusion and Outcome After Transfemoral Transcatheter Aortic Valve Replacement

Objective: To investigate the prognostic impact of red blood cell (RBC) transfusion on the outcome after transfemoral transcatheter aortic valve replacement (TAVR).Design: Nationwide, retrospective multicenter study.Setting: Five University Hospitals.Participants: The nationwide FinnValve registry included data from 2,130 patients who underwent TAVR for aortic stenosis from 2008 to 2017. After excluding patients who underwent TAVR through nontransfemoral accesses, 1,818 patients were selected for this analysis.Intervention: TAVR with or without coronary revascularization.Measurements and Main Results: RBCs were transfused in 293 patients (16.1%). Time-trend analysis showed that the rates of RBC transfusion decreased significantly from 27.5% in 2012 to 10.0% in 2017 (p Conclusions: Patients who received blood transfusion after TAVR had an increased risk of early and late adverse events. These adverse effects were particularly evident with increasing amount of RBC transfusion and operations for excessive bleeding.</p

The effect of bone marrow microenvironment on the functional properties of the therapeutic bone marrow-derived cells in patients with acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Treatment of acute myocardial infarction with stem cell transplantation has achieved beneficial effects in many clinical trials. The bone marrow microenvironment of ST-elevation myocardial infarction (STEMI) patients has never been studied even though myocardial infarction is known to cause an imbalance in the acid-base status of these patients. The aim of this study was to assess if the blood gas levels in the bone marrow of STEMI patients affect the characteristics of the bone marrow cells (BMCs) and, furthermore, do they influence the change in cardiac function after autologous BMC transplantation. The arterial, venous and bone marrow blood gas concentrations were also compared.</p> <p>Methods</p> <p>Blood gas analysis of the bone marrow aspirate and peripheral blood was performed for 27 STEMI patients receiving autologous stem cell therapy after percutaneous coronary intervention. Cells from the bone marrow aspirate were further cultured and the bone marrow mesenchymal stem cell (MSC) proliferation rate was determined by MTT assay and the MSC osteogenic differentiation capacity by alkaline phosphatase (ALP) activity assay. All the patients underwent a 2D-echocardiography at baseline and 4 months after STEMI.</p> <p>Results</p> <p>As expected, the levels of pO₂, pCO₂, base excess and HCO₃were similar in venous blood and bone marrow. Surprisingly, bone marrow showed significantly lower pH and Na⁺and elevated K⁺levels compared to arterial and venous blood. There was a positive correlation between the bone marrow pCO₂and HCO₃levels and MSC osteogenic differentiation capacity. In contrast, bone marrow pCO₂and HCO₃levels displayed a negative correlation with the proliferation rate of MSCs. Patients with the HCO₃level below the median value exhibited a more marked change in LVEF after BMC treatment than patients with HCO₃level above the median (11.13 ± 8.07% vs. 2.67 ± 11.89%, P = 0.014).</p> <p>Conclusions</p> <p>Low bone marrow pCO₂and HCO₃levels may represent the optimal environment for BMCs in terms of their efficacy in autologous stem cell therapy in STEMI patients.</p

Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control

The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson?s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity

Analysis of heart rate dynamics by methods derived from nonlinear mathematics:clinical applicability and prognostic significance

Abstract The traditional methods of analysing heart rate variability based on means and variance are unable to detect subtle but potentially important changes in interbeat heart rate behaviour. This research was designed to evaluate the clinical applicability and prognostic significance of new dynamical methods of analysing heart rate behaviour derived from nonlinear mathematics. The study covered four different patient populations, their controls and one general population of elderly people. The first patient group consisted of 38 patients with coronary artery disease without previous myocardial infarction, the second of 40 coronary artery disease patients with a prior Q-wave myocardial infarction, and the third of 45 patients with a history of ventricular tachyarrhythmia. The fourth group comprised 10 patients with a previous myocardial infarction who had experienced ventricular fibrillation during electrocardiographic recordings. The fifth group comprised a random sample of 347 community-living elderly people invited for a follow-up of 10 years after electrocardiographic recordings. Heart rate variability was analysed by traditional time and frequency domain methods. The new dynamical measures derived from nonlinear dynamics were: 1) approximate entropy, which reflects the complexity of the data, 2) detrended fluctuation analysis, which describes the presence or absence of fractal correlation properties of time series data, and 3) power-law relationship analysis, which demonstrates the distribution of spectral characteristics of RR intervals, but does not reflect the magnitude of spectral power in different spectral bands. Approximate entropy was higher in postinfarction patients (1.17 ± 0.22), but lower in coronary artery disease patients without myocardial infarction (0.93 ± 0.17) than in healthy controls (1.03 ± 014, p &lt; 0.01, p &lt; 0.05 respectively). It did not differ between patients with and without ventricular arrhythmia. The short term fractal-like scaling exponent of the detrended fluctuation analysis was higher in coronary artery disease patients without myocardial infarction (1.34 ± 0.15, p &lt; 0.001), but not in postinfarction patients without arrhythmia (1.06 ± 0.13) compared with healthy controls (1.09 ± 0.13). The short term exponent was markedly reduced in patients with life-threatening arrhythmia (0.85 ± 0.25 ventricular tachycardia patients, 0.68 ± 0.18 ventricular fibrillation patients, p &lt; 0.001 for both). The long term power-law slope of the power-law scaling analysis was lower in the ventricular fibrillation group than in postinfarction controls without arrhythmia risk (-1.63 ± 0.24 vs. -1.33 ± 0.23, p &lt; 0.01) and predicted mortality in a general elderly population with an adjusted relative risk of 1.74 (95% CI 1.42–2.13). The present observations demonstrate that dynamic analysis of heart rate behaviour gives new insight into analysis of heart rate dynamics in various cardiovascular disorders. The breakdown of the normal fractal-like organising principle of heart rate variability is associated with an increased risk of mortality and vulnerability to life-threatening arrhythmias

Antenatal hemodynamic findings and heart rate variability in early school-age children born with fetal growth restriction

Abstract Background: According to epidemiological studies, impaired intrauterine growth increases the risk for cardiovascular morbidity and mortality in adulthood. Heart rate variability (HRV), which reflects the autonomic nervous system function, has been used for risk assessment in adults while its dysfunction has been linked to poor cardiovascular outcome. Objective: We hypothesized that children who were born with fetal growth restriction (FGR) and antenatal blood flow redistribution have decreased HRV at early school age compared to their gestational age matched peers with normal intrauterine growth. Study design: A prospectively collected cohort of children born with FGR (birth weight &lt;10th percentile and/or abnormal umbilical artery flow, n = 28) underwent a 24-hour Holter monitoring at the mean age of 9 years and gestational age matched children with birth weight appropriate for gestational age (AGA, n = 19) served as controls. Time- and frequency domain HRV indices were measured and their associations with antenatal hemodynamic changes were analyzed. Results: Time- and frequency domain HRV parameters (standard deviation of R–R intervals, SDNN; low frequency, LF; high frequency, HF; LF/HF; very low frequency, VLF) did not differ significantly between FGR and AGA groups born between 24 and 40 weeks. Neither did they differ between children born with FGR and normal umbilical artery pulsatility or increased umbilical artery pulsatility. In total, 56% of the FGR children demonstrated blood flow redistribution (cerebroplacental ratio, CPR &lt; −2 SD) during fetal life and their SDNN (p = .01), HF (p = .03) and VLF (p = .03) values were significantly lower than in FGR children with CPR ≥ −2SD. Conclusions: Early school age children born with FGR and intrauterine blood flow redistribution demonstrated altered heart rate variability. These prenatal and postnatal findings may be helpful in targeting preventive cardiovascular measures in FGR