Sebastian Spethmann

Impact of gender on three-month outcome and left ventricular remodeling after transfemoral transcatheter aortic valve implantation.

Transarterial aortic valve implantation (TAVI) is a promising method for the treatment of high-risk patients with aortic stenosis. Because gender differences are known in aortic stenosis, the aim of this study was to compare procedural and short-term outcomes, left ventricular remodeling, and inflammatory status after TAVI in men and women. One hundred consecutive patients (42 men, 58 women) who underwent transfemoral TAVI (CoreValve in 83%, SAPIEN in 17%) were prospectively analyzed. Aortic stenosis severity was higher in women (mean valve area 0.7 ± 0.3 vs 0.8 ± 0.2 cm(2)). Women had better ejection fractions, smaller end-diastolic and end-systolic diameters, and more concentric hypertrophy at baseline. There were no differences in device success rate (99%), 30-day total mortality (2.4% in men, 3.4% in women), stroke (2.4% in men, 1.7% in women), or pacemaker rate (26.2% in men, 15.5% in women). Periprocedural complications and 3-month outcome were not different between the genders. After TAVI, regression of hypertrophy occurred in men and women, but improvement of the ejection fraction was significant only in women. N-terminal pro-B-type natriuretic peptide decreased to similar levels in the 2 genders. C-reactive protein and interleukin-6, elevated at baseline more in men than in women, decreased after TAVI and normalized at 3 months only in women. In conclusion, women clinically benefit from TAVI to a degree similar to that of men. However, there are gender differences involving the recovery response of the left ventricle after TAVI.

Two-dimensional speckle tracking of the left ventricle in patients with systemic sclerosis for an early detection of myocardial involvement

AIMS Myocardial involvement is associated with poor prognosis in patients with systemic sclerosis (SSc). Two-dimensional speckle-tracking echocardiography (STE) is a powerful novel modality for the assessment of subclinical cardiac left ventricular (LV) dysfunction that, so far, has not been investigated in SSc patients. The aim of this study was to evaluate deformation analyses derived from STE for early detection of LV systolic dysfunction in patients with SSc having preserved left ventricular ejection fraction (LVEF). METHODS AND RESULTS Twenty-two patients with SSc (57.1 ± 13.3 years, LVEF 64 ± 3.1%, mean time of 5.4 ± 4.6 years from diagnosis) and 22 gender- and age-matched healthy subjects (57.4 ± 14.0 years, LVEF 65 ± 2.7%) underwent echocardiography with STE to assess global and regional LV function. The global longitudinal 2D peak systolic strain (PSS) of the left ventricle was significantly lower in the SSc group compared with controls: -19.0 ± 2.4 vs. -21.1 ± 2.5% (P = 0.008). This was mainly driven by a reduced strain in the basal segments. Strain in the medial segments and in the apex did not differ significantly. In addition, there was a significant difference between both groups regarding the global longitudinal PSS rate of the left ventricle (-1.19 ± 0.18 vs. -1.43 ± 0.26 s(-1), P = 0.001). CONCLUSION LV deformation analysis by STE is a sensitive method to detect early LV systolic impairment primarily in the basal segments in patients with SSc having preserved LVEF.

Acute regional improvement of myocardial function after interventional transfemoral aortic valve replacement in aortic stenosis: A speckle tracking echocardiography study

BackgroundTranscatheter aortic valve implantation (TAVI) is a promising therapy for patients with severe aortic stenosis (AS) and high perioperative risk. New echocardiographic methods, including 2D Strain analysis, allow the more accurate measurement of left ventricular (LV) systolic function. The goal of this study was to describe the course of LV reverse remodelling immediately after TAVI in a broad spectrum of patients with symptomatic severe aortic valve stenosis.MethodsThirty consecutive patients with symptomatic aortic valve stenosis and preserved LVEF underwent transfemoral aortic valve implantation. We performed echocardiography at baseline and one week after TAVI. Echocardiography included standard 2D and Doppler analysis of global systolic and diastolic function as well as 2D Strain measurements of longitudinal, radial and circumferential LV motion and Tissue Doppler echocardiography.ResultsThe baseline biplane LVEF was 57 ± 8.2%, the mean pressure gradient was 46.8 ± 17.2 mmHg and the mean valve area was 0.73 ± 0.27 cm2. The average global longitudinal 2D strain of the left ventricle improved significantly from -15.1 (± 3.0) to -17.5 (± 2.4) % (p < .001). This was reflected mainly in improvement in the basal and medial segments while strain in the apex did not change significantly [-11.6 (± 5.2) % to -15.1 (± 5.5) % (p < .001), -13.9 (± 5.1) % to -16.8 (± 5.6) % (p < .001) and -19.2 (± 7.0) % to -20.0 (± 7.2) % (p = .481) respectively]. While circumferential strain [-18.1 (± 5.1) % vs. -18.9 (± 4.2) %, p = .607], radial strain [36.5 (± 13.7) % vs. 39.7 (± 17.2) %, p = .458] and the LVEF remained unchanged after one week [57.0 (± 8.2) % vs. 59.1 (± 8.1) %, p = .116].ConclusionThere is an acute improvement of myocardial longitudinal systolic function of the basal and medial segments measured by 2D Strain analysis immediately after TAVI. The radial, circumferential strain and LVEF does not change significantly in all patients acutely after TAVI. These data suggest that sensitive new echo methods can reliably detect early regional changes of myocardial function after TAVI before benefits in LVEF are detectable.

Doppler haemodynamics and effective orifice areas of Edwards SAPIEN and CoreValve transcatheter aortic valves

AIMS Transcatheter aortic valve implantation (TAVI) is a new therapy for severe aortic stenosis in high-risk patients. So far, no reference values for the echocardiographic assessment of this new class of heart valves have been established. The aim of our study was to determine Doppler haemodynamics and the effective orifice area (EOA). METHODS AND RESULTS We retrospectively analysed the earliest transthoracic echocardiographic examinations of 146 stable patients after successful TAVI (median 8±20 days). Doppler examinations were analysed for peak instantaneous velocity, peak, and the mean systolic gradient. EOA was determined using the continuity equation. Patients with severe paravalvular aortic or mitral valve regurgitation were excluded. The overall peak instantaneous velocity (n=146) was 2.0±0.4 m/s with a peak systolic gradient of 17.1±7.4 mmHg and a mean gradient of 9.3±4.5 mmHg. The mean EOA was 1.82±0.43 cm2 with an indexed EOA of 1.0±0.27 cm2/m2. In general, all prostheses showed similar values-with the exception of the Edwards Sapien 23 mm which was associated with higher velocities and peak pressure gradients. CONCLUSION Our study establishes the normal range for Doppler haemodynamics of four transcatheter aortic valve prostheses. Compared with previously published data of surgically implanted bioprostheses percutaneous valves tend to have similar EOA values but lower mean peak velocities and pressure gradients. In comparison with physiological haemodynamics; however, this new class of heart valves is still associated with a mild obstruction.

Galectin-3 predicts short- and long-term outcome in patients undergoing transcatheter aortic valve implantation (TAVI)

Until now, no reliable biomarker has become available for short- or long-term outcome prediction in patients undergoing transcatheter aortic valve implantation (TAVI). Our goal was to investigate whether galectin-3 is also suited for risk assessment in TAVI patients. Galectin-3, a novel marker indicative for myocardial fibrosis, has prognostic value in heart failure. We included 101 patients undergoing TAVI in this prospective, single-center, observational study. Baseline galectin-3 levels were correlated to the VARC 30-day safety and one-year efficacy endpoint as well as to total mortality and cardiovascular events at one year. At baseline, mean galectin-3 level for the entire group was 18.1 (± 11.1) ng/ml. Of the 101 patients, 36 had a galectin-3 value above the cut off value of 17.8 ng/ml. These patients had significantly higher systolic pulmonary artery and capillary wedge pressures. The hazard ratio in patients with galectin-3 > 17.8 ng/ml was 3.36 (95% confidence interval, CI: 1.47-7.69; p=0.004) for the VARC 30-day safety endpoint, 5.12 (95% CI: 2.10-12.47; p<0.001) for one-year cardiovascular events, and 4.48 (95% CI: 1.56-12.91; p=0.005) for all-cause mortality. This prediction remained stable even after adjusting for possible confounders including age, sex, glomerular filtration rate, and NT-proBNP. Furthermore, the prediction was even more valuable when combining galectin-3 with NTproBNP. In summary elevated galectin-3 levels are associated with adverse outcome after TAVI. Combining galectin-3 with NT-proBNP provides additive predictive value of risk stratification.

Recovery of left ventricular and left atrial mechanics in various entities of aortic stenosis 12 months after TAVI

BACKGROUND Transcatheter aortic valve implantation (TAVI) has been shown to improve prognosis of high-risk patients. Data, however, concerning the impact of TAVI on regional and global left atrial (LA) and left ventricular (LV) mechanics in varying entities of severe aortic stenosis (AS) are sparse, particularly in patients with paradoxical low-flow (PLF) AS or with reduced LV ejection fraction (LVEF). This study evaluated the effects of TAVI on LA and LV mechanics in varying entities of AS 12 months after implantation. METHODS AND RESULTS A total of 54 consecutive patients with severe AS (24 with a normal LVEF and normal flow, 16 with PLF, and 14 with a reduced LVEF) were included. Speckle tracking echocardiography was performed before and 12 months after TAVI to determine LV global and regional longitudinal deformation as well as LA function (reservoir function, conduit phase, and active contraction). In all the three entities of AS, there was a significant improvement in global and regional LV longitudinal function (average global longitudinal strain: -14.1 ± 3.9% at baseline vs. -16.5 ± 4.0% after TAVI, P < 0.001). Interestingly, the beneficial effects were most pronounced in patients with PLF (-14.0 ± 2.9 vs. -17.0 ± 4.4%, P < 0.031). Moreover, the atrial reservoir and conduit function recovered significantly after TAVI in all patients. CONCLUSION In conclusion, regardless of the underlying AS entity, TAVI improves global and regional LV and LA mechanics within 12 months.

Exercise-induced changes of left ventricular diastolic function in postmenopausal amateur marathon runners: assessment by echocardiography and cardiac biomarkers

Purpose Diastolic dysfunction is common among elderly women. Recently, concerns regarding marathon-induced myocardial damage were raised among young male runners. The goal of our study was to assess the impact of marathon running on systolic and diastolic ventricular function before and immediately after completing a marathon among postmenopausal well-trained amateur women. Methods A total of 89 female runners of the Berlin Marathon were included (35 postmenopausal and 54 premenopausal female controls) and examined before, immediately, and 2 weeks after the race by echocardiography (including tissue Doppler- and 2D strain speckle tracking) and underwent blood tests. Results After the marathon, there was a significant increase in E/E′ (postmenopausal 8.5 ± 2.3 vs. 10.9 ± 3.2 post race; control: 8.1 ± 1.8 vs. 9.9 ± 2.9 post race, p < 0.001) and a decrease in E/A in both groups (postmenopausal 1.3 ± 0.36 vs. 0.9 ± 0.21 post race; control 1.7 ± 0.6 vs. 1.1 ± 0.3; p < 0.001). In contrast, regardless of the hormonal status the atrial contraction increased significantly. Left and right ventricular systolic contractility, as assessed by speckle tracking and pulsed-wave tissue Doppler velocities, showed a significant increase in both groups. Of all runners, 55 (61.8%) experienced increases in troponin T and/or N-terminal-B-type natriuretic peptide after the race. All echocardiographic and laboratory parameters returned to normal within 2 weeks. Conclusions 2D strain analysis of the left and right ventricles showed an acute improvement of the systolic function after marathon running in pre- and postmenopausal well-trained women. There were no long lasting detrimental effects on the diastolic function.

Improved Left Ventricular Structure and Function After Successful Kidney Transplantation

Background/Aims: Cardiac changes observed in chronic kidney disease patients are of multifactorial origin including chronic uremia, hemodynamics or inflammation. Restoration of renal function by kidney transplantation (KTX) may reverse cardiac changes. Novel echocardiographic methods such as speckle tracking echocardiography (STE) allow early and sensitive detection of subtle changes of cardiac parameters. We evaluated changes of cardiac structure and function after KTX by advanced echocardiographic modalities. Methods: Thirty-one KTX recipients (female n=11) were evaluated by medical examination, laboratory testing and echocardiography before and after KTX (median follow-up 19 months). Left ventricular (LV) and right ventricular (RV) diameters and function were assessed by echocardiographic standard parameters. Longitudinal 2D strain of the LV (GLPS) and left atrium (LA) was determined by 2D STE. Results: After KTX, median serum creatinine level was 1.3 mg/dl (IQR, 1.2-1.5). Systolic blood pressure decreased significantly after KTX. Echocardiography showed a significant reduction in LV end-diastolic septal and posterior wall thickness and LV mass index after KTX, which was accompanied by an improvement of GLPS. There were no relevant changes in parameters of LA (reservoir, conduit or contractile) function, LV diastolic or RV function after KTX. Conclusion: LV hypertrophy reversed after successful KTX and was accompanied by an improvement in longitudinal LV function as assessed by STE. Diastolic function and STE-derived LA function parameters did not change significantly after KTX.

Galectin-3 increase in endurance athletes

Background Galectin-3 is a new and promising biomarker for heart failure and myocardial fibrosis. Although endurance exercise is a crucial element in cardiovascular disease prevention, the relationship between exercise and plasma levels of galectin-3 is still unknown. To date, the relationship between regular exercise and myocardial fibrosis is not fully understood. This study investigates the relationship between endurance exercise and plasma levels of galectin-3. Methods Twenty-one male, healthy non-elite marathon runners were examined before and within 1 hour after a strenuous run of 30 km after 4-day training abstinence. Examination included blood samples for galectin-3, echocardiography, and cardiac magnetic resonance imaging (CMR). In addition, to distinguish between cardiac or skeletal muscular origin of galectin-3, 27 C57Bl/6 J mice performing voluntary wheel running and 25 sedentary mice were analysed. Results Plasma galectin-3 in endurance athletes increased from baseline to post exercise (12.8 ± 3.4 ng/ml to 19.9 ± 3.9 ng/ml, p < 0.001) while the systolic left and right ventricular function remained unchanged. Interestingly, baseline plasma levels of galectin-3 were in normal range but higher than in healthy sedentary controls. However, in CMR there was no correlation between baseline galectin-3 levels and the detection of myocardial fibrosis. In animal studies, the relative level of mRNA for galectin-3 in active mice was significantly higher compared to sedentary mice. This increase was most pronounced in skeletal muscle (98.0% higher, p < 0.001) and not in the myocardium of the left ventricle (19.9% higher, p = 0.043). Conclusions Plasma galectin-3 is substantially elevated in endurance athletes after running but does not correlate with cardiac function, other biomarkers, or myocardial fibrosis. In mice, we demonstrate that galectin-3 increase during endurance exercise originates primarily from skeletal muscle.

Dyssynchrony parameter-guided interventricular delay programming

AIMS Interventricular (VV) delay optimization for cardiac resynchronization therapy (CRT) is recommended by current guidelines and several algorithms have been proposed. So far, however, no gold standard has been established in the clinical routine. We hypothesized that dyssynchrony parameter assessment might guide VV delay optimization and investigated whether dyssynchrony parameter changes induced by sequential biventricular pacing follow a predictable pattern. METHODS AND RESULTS We determined intra- and interventricular dyssynchrony in 80 CRT patients by echocardiographic quantification of the interventricular mechanical delay and the septal-lateral time to peak systolic velocity delay. Dyssynchrony parameters were assessed during simultaneous biventricular pacing as well as during sequential biventricular pacing with a right ventricular (RV) or left ventricular (LV) preactivation of 40 ms. Simultaneous biventricular pacing significantly improved inter- and intraventricular dyssynchrony parameters compared with preoperative baseline measurements. In general, dyssynchrony parameter changes induced by sequential biventricular pacing showed high interindividual variance and did not follow a predictable pattern. Intra- or interventricular dyssynchrony persisted during simultaneous biventricular pacing in 39 and 19% of our patients, respectively. Neither RV nor LV preactivation significantly decreased the number of patients with persistent intraventricular dyssynchrony. In contrast, LV preactivation significantly reduced the prevalence of interventricular dyssynchrony by 80%. CONCLUSIONS Left ventricular preactivation effectively ameliorates interventricular dyssynchrony, which persists in almost one in five CRT patients. Assessment of interventricular dyssynchrony and consecutive programming of LV preactivation in patients with persistent interventricular dyssynchrony may represent a pragmatic and time-effective approach to improve CRT in patients with inferior response.