58 research outputs found
Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction
AbstractObjectivesThe objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF.BackgroundIncreased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Baroreflex activation therapy (BAT) results in centrally mediated reduction of sympathetic outflow and increased parasympathetic activity.MethodsPatients with New York Heart Association (NYHA) functional class III HF and ejection fractions â¤35% on chronic stable guideline-directed medical therapy (GDMT) were enrolled at 45 centers in the United States, Canada, and Europe. They were randomly assigned to receive ongoing GDMT alone (control group) or ongoing GDMT plus BAT (treatment group) for 6 months. The primary safety end point was system- and procedure-related major adverse neurological and cardiovascular events. The primary efficacy end points were changes in NYHA functional class, quality-of-life score, and 6-minute hall walk distance.ResultsOne hundred forty-six patients were randomized, 70 to control and 76 to treatment. The major adverse neurological and cardiovascular eventâfree rate was 97.2% (lower 95% confidence bound 91.4%). Patients assigned to BAT, compared with control group patients, experienced improvements in the distance walked in 6 min (59.6 Âą 14 m vs. 1.5 ¹ 13.2 m; p = 0.004), quality-of-life score (â17.4 Âą 2.8 points vs. 2.1 Âą 3.1 points; p < 0.001), and NYHA functional class ranking (p = 0.002 for change in distribution). BAT significantly reduced N-terminal proâbrain natriuretic peptide (p = 0.02) and was associated with a trend toward fewer days hospitalized for HF (p = 0.08).ConclusionsBAT is safe and improves functional status, quality of life, exercise capacity, N-terminal proâbrain natriuretic peptide, and possibly the burden of heart failure hospitalizations in patients with GDMT-treated NYHA functional class III HF. (Barostim Neo System in the Treatment of Heart Failure; NCT01471860; Barostim HOPE4HF [Hope for Heart Failure] Study; NCT01720160
Transforming Growth Factor β1 Oppositely Regulates the Hypertrophic and Contractile Response to β-Adrenergic Stimulation in the Heart
BACKGROUND: Neuroendocrine activation and local mediators such as transforming growth factor-βâ (TGF-βâ) contribute to the pathobiology of cardiac hypertrophy and failure, but the underlying mechanisms are incompletely understood. We aimed to characterize the functional network involving TGF-βâ, the renin-angiotensin system, and the β-adrenergic system in the heart. METHODS: Transgenic mice overexpressing TGF-βâ (TGF-βâ-Tg) were treated with a β-blocker, an ATâ-receptor antagonist, or a TGF-β-antagonist (sTGFβR-Fc), were morphologically characterized. Contractile function was assessed by dobutamine stress echocardiography in vivo and isolated myocytes in vitro. Functional alterations were related to regulators of cardiac energy metabolism. RESULTS: Compared to wild-type controls, TGF-βâ-Tg mice displayed an increased heart-to-body-weight ratio involving both fibrosis and myocyte hypertrophy. TGF-βâ overexpression increased the hypertrophic responsiveness to β-adrenergic stimulation. In contrast, the inotropic response to β-adrenergic stimulation was diminished in TGF-βâ-Tg mice, albeit unchanged basal contractility. Treatment with sTGF-βR-Fc completely prevented the cardiac phenotype in transgenic mice. Chronic β-blocker treatment also prevented hypertrophy and ANF induction by isoprenaline, and restored the inotropic response to β-adrenergic stimulation without affecting TGF-βâ levels, whereas ATâ-receptor blockade had no effect. The impaired contractile reserve in TGF-βâ-Tg mice was accompanied by an upregulation of mitochondrial uncoupling proteins (UCPs) which was reversed by β-adrenoceptor blockade. UCP-inhibition restored the contractile response to β-adrenoceptor stimulation in vitro and in vivo. Finally, cardiac TGF-βâ and UCP expression were elevated in heart failure in humans, and UCP--but not TGF-βâ--was downregulated by β-blocker treatment. CONCLUSIONS: Our data support the concept that TGF-βâ acts downstream of angiotensin II in cardiomyocytes, and furthermore, highlight the critical role of the β-adrenergic system in TGF-βâ-induced cardiac phenotype. Our data indicate for the first time, that TGF-βâ directly influences mitochondrial energy metabolism by regulating UCP3 expression. β-blockers may act beneficially by normalizing regulatory mechanisms of cellular hypertrophy and energy metabolism
An early analysis of cost-utility of baroreflex activation therapy in advanced chronic heart failure in Germany
Abstract Background This study aimed to evaluate cost-utility of baroreflex activation therapy (BAT) using the Barostim neo⢠device (CVRx Inc., Minneapolis, MN, USA) compared with optimized medical management in patients with advanced chronic heart failure (NYHA class III) who were not eligible for treatment with cardiac resynchronization therapy, from a statutory health insurance perspective in Germany over a lifetime horizon. Methods A decision analytic model was developed using the combination of a decision tree and the Markov process. The model included transitions between New York Heart Association (NYHA) health states, each of which is associated with a risk of mortality, hospitalization, cost, and quality of life. The effectiveness of BAT was projected through relative risks for mortality (obtained by application of patient-level data to the Meta-analysis Global Group in Chronic Heart Failure risk prediction model) and hospitalization owing to worsening of heart failure (obtained from BAT Randomized Clinical Trial). All patients were in NYHA class III at baseline. Results BAT led to an incremental cost of âŹ33,185 (95% credible interval [CI] âŹ24,561â38,637) and incremental benefits of 1.78 [95% CI 0.45â2.71] life-years and 1.19 [95% CI 0.30â1.81] quality-adjusted life-years (QALYs). This resulted in an incremental cost-effectiveness ratio of âŹ27,951/QALY (95% CI âŹ21,357â82,970). BAT had a 59% probability of being cost-effective at a willingness-to-pay threshold of âŹ35,000/QALY (but 84% at a threshold of âŹ52,000/QALY). Conclusions BAT can be cost-effective in European settings in those not eligible for cardiac resynchronization therapy among patients with advanced heart failure
Akute Aortendissektion: Ein lebensbedrohlicher Notfall auch in der neurologischen Notfallmedizin
Acute aortic dissection is rare but life-threatening. The symptoms depend on the localization and reduced perfusion of the downstream organs or limbs and are therefore variable. Neurological symptoms may occur that do not immediately lead to a diagnosis and thus delay the necessary therapy. Knowing the early symptoms and warning signs of aortic dissection is therefore also crucial in neurological emergency care for quickly identifying the affected patients and for providing acute therapy. A misdiagnosis with delayed initiation of therapy can significantly worsen the patient's outcome. This study aims to establish a standardized diagnostic and therapeutic algorithm for suspected acute aortic dissection in neurological emergency care. Close interdisciplinary cooperation is mandatory
Postinterventional iatrogenic atrial septal defect with hemodynamically relevant left-to-right and right-to-left shunt as a complication of successful percutaneous mitral valve repair with the MitraClip
Optimierung, Standardisierung und Validierung der Methodik der Präparation neonataler muriner myokardialer Gewebeschnitte zur Durchfßhrung elektrophysiologischer Untersuchungen
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