One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction

Background—Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results—Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions—These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations

Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM-HFpEF study.

BackgroundApproximately half of the patients presenting with new-onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid-range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta-blockers and angiotensin-converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy. Beneficial effects of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) have also been observed in several animal models of HFpEF, suggesting a potential role for ART in patients with this disease.MethodsThe Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Patients with Heart Failure and Preserved Ejection Fraction (ANTHEM-HFpEF) study is designed to evaluate the feasibility, tolerability, and safety of ART using right cervical VNS in patients with chronic, stable HFpEF and HFmrEF. Patients with symptomatic HF and HFpEF or HFmrEF fulfilling the enrolment criteria will receive chronic ART with a subcutaneous VNS system attached to the right cervical vagus nerve. Safety parameters will be continuously monitored, and cardiac function and HF symptoms will be assessed every 3 months during a post-titration follow-up period of at least 12 months.ConclusionsThe ANTHEM-HFpEF study is likely to provide valuable information intended to expand our understanding of the potential role of ART in patients with chronic symptomatic HFpEF and HFmrEF

Comparison between tagged MRI and standard cine MRI for evaluation of left ventricular ejection fraction

Global left ventricular function is a prognostic indicator and is used to evaluate therapeutical interventions in patients with heart failure. Regional left ventricular function can be determined with tagged MRI. Assessment of global left ventricular function using the tagging data may have additional clinical value without incurring extra scanning time, which is currently a limiting factor in cardiac imaging. Direct determination of end-diastolic volume is not possible with conventional tagged MRI. However, end-systolic volume can be directly measured because myocardium-blood contrast improves through a tagged image series. We investigated the potential of tagged MRI using frequency-domain analysis software to retrospectively track end-diastolic contour from end-systolic contour and subsequently calculate the ejection fraction. Tagged MRI was compared with the standard bright-blood cine MRI in healthy volunteers (n=20) and patients with previous myocardial infarction (n=8). Left ventricular ejection fraction derived from tagged MRI is linearly correlated to left ventricular ejection fraction obtained by standard cardiac cine MRI (y=1.0x+1.31, r>0.98, p=0.014). In addition, the inter-observer and intra-observer coefficient of variation for left ventricular ejection fraction measurements was low (CVintra=0.4%, CVinter=1.3%). With tagged MRI, only end-systolic volume needs to be manually determined, and accurate estimation of left ventricular ejection fraction is obtained because end-diastolic and end-systolic volumes are determined using identical anatomical points. Our data indicate that tagged MRI can be used to quantitatively assess both regional and global left ventricular function. Therefore, tagged MRI may be a valuable clinical tool for determining the prognosis and evaluating the effect of therapeutical intervention using a single imaging session in patients with left ventricular dysfunctio

Left ventricular systolic function evaluated by strain echocardiography and relationship with mortality in patients with severe sepsis or septic shock. a systematic review and meta-analysis

Sepsis-induced myocardial dysfunction is associated with poor outcomes, but traditional measurements of systolic function such as left ventricular ejection fraction (LVEF) do not directly correlate with prognosis. Global longitudinal strain (GLS) utilizing speckle-tracking echocardiography (STE) could be a better marker of intrinsic left ventricular (LV) function, reflecting myocardial deformation rather than displacement and volume changes. We sought to investigate the prognostic value of GLS in patients with sepsis and/or septic shock

The Value of Right Ventricular Longitudinal Strain in the Evaluation of Adult Patients With Repaired Tetralogy of Fallot: a New Tool for a Contemporary Challenge

OBJECTIVE: The role of right ventricular longitudinal strain for assessing patients with repaired tetralogy of Fallot is not fully understood. In this study, we aimed to evaluate its relation with other structural and functional parameters in these patients. METHODS: Patients followed-up in a grown-up CHD unit, assessed by transthoracic echocardiography, cardiac MRI, and treadmill exercise testing, were retrospectively evaluated. Right ventricular size and function and pulmonary regurgitation severity were assessed by echocardiography and MRI. Right ventricular longitudinal strain was evaluated in the four-chamber view using the standard semiautomatic method. RESULTS: In total, 42 patients were included (61% male, 32±8 years). The mean right ventricular longitudinal strain was -16.2±3.7%, and the right ventricular ejection fraction, measured by MRI, was 42.9±7.2%. Longitudinal strain showed linear correlation with tricuspid annular systolic excursion (r=-0.40) and right ventricular ejection fraction (r=-0.45) (all p<0.05), which in turn showed linear correlation with right ventricular fractional area change (r=0.50), pulmonary regurgitation colour length (r=0.35), right ventricular end-systolic volume (r=-0.60), and left ventricular ejection fraction (r=0.36) (all p<0.05). Longitudinal strain (β=-0.72, 95% confidence interval -1.41, -0.15) and left ventricular ejection fraction (β=0.39, 95% confidence interval 0.11, 0.67) were independently associated with right ventricular ejection fraction. The best threshold of longitudinal strain for predicting a right ventricular ejection fraction of <40% was -17.0%. CONCLUSIONS: Right ventricular longitudinal strain is a powerful method for evaluating patients with tetralogy of Fallot. It correlated with echocardiographic right ventricular function parameters and was independently associated with right ventricular ejection fraction derived by MRI.info:eu-repo/semantics/publishedVersio

Relation of atrial natriuretic peptides to left ventricular systolic and diastolic function in heart failure

Background: Plasma concentrations of atrial natriuretic peptides are correlated with atrial pressures, as are left ventricular ejection fraction and left ventricular filling abnormalities. Aims: This study investigated the relation of atrial natriuretic peptides to both left ventricular systolic and diastolic function in heart failure. Methods: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were measured in 63 patients with chronic heart failure and left ventricular systolic dysfunction. According to Doppler transmitral flow measurements, 19 patients had a restrictive and 44 patients had a non-restrictive left ventricular filling pattern. Results: Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide were higher in patients with a restrictive filling pattern than in patients with a non-restrictive filling pattern (197 vs. 75 pmol/l, P < 0.0001 and 1.14 vs. 0.45 nmol/l, P < 0.0001). In univariate analysis, atrial natriuretic peptide and N-terminal pro-atrial natriuretic peptide correlated with deceleration time, E/A ratio and left ventricular ejection fraction. In multivariate analysis, both peptides appeared independently related to left ventricular ejection fraction and left ventricular filling pattern. Conclusion: In patients with chronic heart failure, atrial natriuretic peptides provide information on left ventricular systolic as well as diastolic function

Assessment of poststress left ventricular ejection fraction by gated SPECT: comparison with equilibrium radionuclide angiocardiography

PURPOSE: We compared left ventricular (LV) ejection fraction obtained by gated SPECT with that obtained by equilibrium radionuclide angiocardiography in a large cohort of patients. METHODS: Within 1 week, 514 subjects with suspected or known coronary artery disease underwent same-day stress-rest (99m)Tc-sestamibi gated SPECT and radionuclide angiocardiography. For both studies, data were acquired 30 min after completion of exercise and after 3 h rest. RESULTS: In the overall study population, a good correlation between ejection fraction measured by gated SPECT and by radionuclide angiocardiography was observed at rest (r=0.82, p<0.0001) and after stress (r=0.83, p<0.0001). In Bland-Altman analysis, the mean differences in ejection fraction (radionuclide angiocardiography minus gated SPECT) were -0.6% at rest and 1.7% after stress. In subjects with normal perfusion (n=362), a good correlation between ejection fraction measured by gated SPECT and by radionuclide angiocardiography was observed at rest (r=0.72, p<0.0001) and after stress (r=0.70, p<0.0001) and the mean differences in ejection fraction were -0.9% at rest and 1.4% after stress. Also in patients with abnormal perfusion (n=152), a good correlation between the two techniques was observed both at rest (r=0.89, p<0.0001) and after stress (r=0.90, p<0.0001) and the mean differences in ejection fraction were 0.1% at rest and 2.5% after stress. CONCLUSION: In a large study population, a good agreement was observed in the evaluation of LV ejection fraction between gated SPECT and radionuclide angiocardiography. However, in patients with perfusion abnormalities, a slight underestimation in poststress LV ejection fraction was observed using gated SPECT as compared to equilibrium radionuclide angiocardiography

Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure

[Abstract] Epicardial adipose tissue has been proposed to participate in the pathogenesis of heart failure. The aim of our study was to assess the expression of thermogenic genes (Uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and PR-domain-missing 16 (PRDM16) in epicardial adipose tissue in patients with heart failure, stablishing the difference according to left ventricular ejection fraction (reduced or preserved). Among the 75 patients in our study, 42.7% (n=32) had reduced left ventricular ejection fraction. UCP1, PGC1α and PRDM16 mRNA in EAT were significantly lower in patients with reduced left ventricular ejection fraction. Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1α and PRDM16 mRNA. Thermogenic genes expressions in epicardial adipose tissue (UCP1: OR 0.617, 95%CI 0.103-0.989, p=0.042; PGC1α: OR 0.416, 95%CI 0.171-0.912, p=0.031; PRDM16: OR 0.643, 95%CI 0.116-0.997, p=0.044) were showed as protective factors against the presence of heart failure with reduced left ventricular ejection fraction, and age (OR 1.643, 95%CI 1.001-3.143, p=0.026), presence of coronary artery disease (OR 6.743, 95%CI 1.932-15.301, p<0.001) and type-2-diabetes mellitus (OR 4.031, 95%CI 1.099-7.231, p<0.001) were associated as risk factors. The adequate expression of thermogenic genes has been shown as possible protective factors against heart failure with reduced ejection fraction, suggesting that a loss of functional epicardial adipose tissue brown-like features would participate in a deleterious manner on heart metabolism. Thermogenic genes could represent a future novel therapeutic target in heart failure.Ministerio de Salud, Servicios Sociales e Igualdad; PI13/02542Ministerio de Salud, Servicios Sociales e Igualdad; PI11/01661Red de Investigación Cardiovascular (España), RD12/0042/003

Interleukin-18 mediates cardiac dysfunction induced by western diet independent of obesity and hyperglycemia in the mouse

Obesity and diabetes are independent risk factors for heart failure and are associated with the consumption of diet rich in saturated fat and sugar, Western diet (WD), known to induce cardiac dysfunction in the mouse through incompletely characterized inflammatory mechanisms. We hypothesized that the detrimental cardiac effects of WD are mediated by interleukin-18 (IL-18), pro-inflammatory cytokine linked to cardiac dysfunction. C57BL/6J wild-type male mice and IL-18 knockout male mice were fed high-saturated fat and high-sugar diet for 8 weeks. We measured food intake, body weight and fasting glycemia. We assessed left ventricular (LV) systolic and diastolic function by Doppler echocardiography and cardiac catheterization. In wild-type mice, WD induced a significant increase in isovolumetric relaxation time, myocardial performance index and left ventricular end-diastolic pressure, reflecting an impairment in diastolic function, paired with a mild reduction in LV ejection fraction. IL-18 KO mice had higher food intake and greater increase in body weight without significant differences in hyperglycemia. Despite displaying greater obesity, IL-18 knockout mice fed with WD for 8 weeks had preserved cardiac diastolic function and higher left ventricular ejection fraction. IL-18 mediates diet-induced cardiac dysfunction, independent of food intake and obesity, thus highlighting a disconnect between the metabolic and cardiac effects of IL-18

Non-invasive quantification of exercise-induced changes in regional left ventricular function in normals and patients with one vessel coronary artery disease using radionuclide ventriculography

To quantitate changes in regional left ventricular function induced by ischemia or scar, rest and exercise equilibrium radionuclide studies of 26 patients with one vessel coronary artery disease and 12 normal individuals were analysed with a new method for regional ejection fraction determination. A computer algorithm provided observer-independent segmental analysis from a centre of gravity of the left ventricular activity at end-diastole (left anterior oblique projection). Special segments were assigned for anteroseptal, inferoapical and posterolateral areas corresponding to the three main coronary arteries. Reproducibility using an unchanged camera positioning was excellent even for 2 min acquisition studies (r=0.93) and still good after repositioning (r=0.80 to 0.87). In normal areas, regional ejection fraction increased or showed no change during exercise. In contrast, it decreased significantly in regions supplied by stenosed coronary arteries (ischemia) and remained depressed in scar zones. The method proved to be valid for regional changes induced by left anterior descending and left circumflex coronary obstructions, but less for right coronary artery lesions. Global ejection fraction reflected a sum of all regional changes implying that regional analysis should be more sensitive in detecting coronary artery diseas