Mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) in severe aortic valve stenosis: association with outcome after transcatheter aortic valve implantation (TAVI).

BACKGROUND: This study aimed to assess the association of mid-regional (MR) pro-adrenomedullin (MR-proADM) and MR-pro-A-type natriuretic peptide (MR-proANP) in comparison to N-terminal pro-natriuretic peptide (NT-proBNP) with outcome in patients with aortic stenosis (AS) treated with transcatheter aortic valve implantation (TAVI). METHODS: One hundred consecutive TAVI patients were included in this prospective study. Association of preinterventional levels of MR-proADM, MR-proANP, NT-proBNP, C-reactive protein (CrP), and high-sensitive cardiac Troponin T (hsTN) with 30-day and 1-year outcome was analyzed. RESULTS: There was no association with 30-day outcome, but all markers were associated with 1-year cardiovascular events and all-cause mortality. The combined biomarker analysis further improved risk prediction. CONCLUSIONS: In TAVI patients MR-proADM, MR-proANP, and NT-proBNP are promising predictors of adverse events within 1 year. Integration of these biomarkers into decision pathways may help to identify patients at higher risk.

Epigenetic suppression of iNOS expression in human endothelial cells: A potential role of Ezh2-mediated H3K27me3.

OBJECTIVE: Cytokines strongly induce expression of the inducible nitric oxide synthase (iNOS) in rodent but not in human endothelial cells. We recently identified NOS2 as a potential target of the histone methyltransferase enhancer of zeste homolog 2 which mediates trimethylation of histone 3 at lysine 27 (H3K27me3). METHODS AND RESULTS: Compared to an unspecific IgG control, chromatin immunoprecipitation using a H3K27me3-specific antibody followed by DNA quantification by PCR showed a strong DNA enrichment - indicating that NOS2 is associated with H3K27me3 in human umbilical vein endothelial cells (HUVEC). siRNA-mediated knock down of Ezh2 diminished NOS2 DNA enrichment - suggesting that the association of NOS2 with H3K27me3 is mediated by Ezh2. Ezh2 knock down, however, was not sufficient to increase iNOS expression after stimulation of HUVEC. CONCLUSION: NOS2 is associated with Ezh2-mediated H3K27me3 in HUVEC. This might contribute to an epigenetic suppression of iNOS inducibility in human endothelial cells.

Staged Catheter-Based Valve Treatment of Severe Carcinoid Heart Disease.

PURPOSE: Carcinoid heart disease (CHD) with severe valve destruction represents the major cause of high morbidity and mortality in patients with carcinoid syndrome. In this paper, we present a novel interventional treatment approach and report the first clinical result achieved in a patient with extensive CHD. METHODS AND RESULTS: A woman with an ileal neuroendocrine tumour (G2, Ki67: 5%) presented with severe CHD (NYHA IV) affecting both the pulmonary and the tricuspid valve. First, a balloon-expandable 23-mm Edwards SAPIEN™ was successfully implanted percutaneously into the pulmonary valve. Since no catheter-based techniques were available for the replacement of the native tricuspid valve, we implanted an Edwards SAPIEN 26-mm valve into the vena cava inferior between the right atrium and the ostium of the hepatic veins to reduce abdominal congestion. The implantation was technically successful and completely prevented regurgitation into the vena cava inferior and abdominal veins. After this procedure, the patient's clinical condition improved significantly, and she achieved near-normal exercise tolerance (VO2 max: 24.4 ml O2/kg/min, NYHA II). CONCLUSION: We demonstrated that percutaneous valve implantation may offer a novel, minimally invasive option in high-risk patients with severe CHD.

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.

Comparison of effects of OSA treatment by MAD and by CPAP on cardiac autonomic function during daytime.

PURPOSE: The present study compared the effects of mandibular advancement therapy (MAD) with continuous positive airway pressure therapy (CPAP) on daytime cardiac autonomic modulation in a wide range of obstructive sleep apnea (OSA) patients under controlled conditions in a randomized, two-period crossover trial. METHODS: Forty OSA patients underwent treatment with MAD and with CPAP for 12 weeks each. At baseline and after each treatment period, patients were assessed by polysomnography as well as by a daytime cardiac autonomic function test that measured heart rate variability (HRV), continuous blood pressure (BP), and baroreceptor sensitivity (BRS) under conditions of spontaneous breathing, with breathing at 6, 12, and 15/min. RESULTS: Both CPAP and MAD therapy substantially eliminated apneas and hypopneas. CPAP had a greater effect. During daytime with all four conditions of controlled breathing, three-minute mean values of continuous diastolic BP were significantly reduced for both MAD and CPAP therapy. At the same time, selective increases due to therapy with MAD were found for HRV high frequency (HF) values. No changes were observed for BRS in either therapy mode. CONCLUSIONS: These findings indicate that both MAD and CPAP result in similar beneficial changes in cardiac autonomic function during daytime, especially in blood pressure. CPAP is more effective than MAD in eliminating respiratory events.

Galectin-3 and prediction of therapeutic response to renal sympathetic denervation.

The profibrotic mediator Galectin-3 (Gal-3) has been associated with aldosterone-mediated vascular inflammation, fibrosis, and stiffness. We evaluated whether the Gal-3 levels and change in Gal-3 as associated with renal denervation can serve as prediction of therapeutic response to renal denervation. A total of 42 patients with resistant hypertension undergoing renal sympathetic denervation (RDN) were included. Blood pressure was evaluated by 24-h ambulatory measurement before RDN and 1, 3 and 6 months after RDN. Treatment response was defined as a drop in systolic ambulatory blood pressure of >5 mm Hg after 6 months. Blood samples were assessed for Gal-3 levels. For the entire group, a significant drop in mean systolic ambulatory blood pressure of 5.2 ± 18.6 mm Hg was observed (p = 0.032). The responder rate was 50% (n = 21). At baseline, Gal-3 levels were significantly higher in responders (14.5 ± 6.0 vs. 10.95 ± 4.6 ng/ml, p = 0.017). There were no significant changes of Gal-3 levels during the follow-up period. The profibrotic biomarker may help to identify patients suitable for RDN.

Endothelial NO Production Is Mandatory for Epigallocatechin-3-Gallate-induced Vasodilation: Results From eNOS Knockout (eNOS-/-) Mice.

The underlying mechanisms for the vasodilating effects of the tea catechin epigallocatechin-3-gallate (EGCG) are still not fully understood. Besides nitric oxide (NO)-dependent effects, other modes of action are discussed. To elucidate whether the NO pathway is a prerequisite in mediating vasodilating effects, we investigated EGCG-induced vasorelaxation in isolated aortic rings of endothelial nitric oxide knockout (eNOS) mice. Vasodilation to acetylcholine was fully prevented in aortic rings of eNOS mice, confirming lack of vascular NO production. Vasodilation to the exogenous NO donor sodium nitroprusside was preserved in eNOS mice aortic rings. Low concentrations of EGCG (5-15 µM) resulted in strong vasorelaxation in aortic rings of wild type mice, whereas it was completely absent in eNOS mice. In corroboration, relaxation in response to green tea was significantly inhibited in aortic rings of eNOS mice. These results demonstrate that EGCG-induced vasodilation strongly relies on functional NO synthase in endothelial cells and subsequent stimulation of NO production in vessels.

Cardiac and renal function in a large cohort of amateur marathon runners.

BACKGROUND: Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. METHODS: A total of 167 participants of the Berlin-Marathon (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). RESULTS: Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. CONCLUSIONS: The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function.

Influence of sex on outcome following transcatheter aortic valve implantation (TAVI): systematic review and meta-analysis.

BACKGROUND: Sex differences exist in pathogenesis, clinical presentation, and outcome in aortic stenosis (AS). However, only limited information is available concerning sex differences in transcatheter aortic valve implantation (TAVI). The aim of the present study is a comprehensive meta-analysis of studies that investigate differences between men and women in outcome after TAVI. METHODS: We screened PUBMED, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Inclusion criteria were: AS treated with all forms of TAVI, studies specifically targeting sex/gender differences, and at least 2 of the following outcome data: 30-day all-cause death, mortality during follow-up, major vascular complications, major bleeding, pacemaker, or stroke rate (<30 days). Studies were excluded if they considered female gender merely in subgroup analysis. RESULTS: We included 14 observational studies with a total of 7,973 patients (4,242 women, 3,731 men). At 30 days (12 studies, 3,044 women, 2,784 men), female sex was associated with a significantly lower mortality rate (odds ratio [95% confidence interval] 0.78 [0.64, 0.96]). Of the 14 studies included for analysis, 12 provided data on mortality during follow-up that likewise show a survival advantage for women (OR 0.70 [0.59, 0.82]). Whereas the major vascular complication rate was greater in women (11 studies, 3,731 women, 3,342 men; OR 1.72 [1.41, 2.09]), major bleeding (8 studies, 2,124 women, 2,100 men; OR 1.13 [0.95, 1.33]) was not. Pacemaker and stroke rate were not significantly different between the groups. CONCLUSION: In treatment with TAVI, there is evidence for a significantly greater overall survival benefit in women over men.

Effect of ivabradine-induced heart rate reduction on flow-mediated dilation measured with high-sensitivity ultrasound in patients with stable coronary heart disease.

BACKGROUND: Experimental data suggests that exclusive heart rate reduction with ivabradine is associated with the amelioration of the endothelial function. Since it is presently unknown whether this also applies to humans, the aim of this pilot study was to investigate whether heart rate reduction with ivabradine modulates the endothelial function in humans with an established coronary heart disease. METHODS: Using high-sensitivity ultrasound, we analysed the flow-mediated (FMD) and nitro-mediated dilation (NMD) of the brachial artery in 25 patients (62.9 ± 8.4 years) with a stable coronary heart disease and a resting heart rate of ≥70 beats per minute (bpm). To assess acute effects, measurements were performed before and 4 hours after the first intake of ivabradine 7.5 mg. Sustained effects of an ivabradine therapy (5 mg to 7.5 mg twice daily) were investigated after 4 weeks. RESULTS: We found a significant decrease in heart rate, both 4 hours after the intake of 7.5 mg of ivabradine (median -8 [interquartile range (IQR) -14 to -4] bpm) and after 4 weeks of twice daily intake (median -10 [IQR-17 to -5] bpm) (p < 0.05). However, the FMD did not change significantly: neither after first dose of ivabradine nor after sustained therapy (baseline FMD: median 5.0 [IQR 2.4 to 7.9]%; FMD 4 hours after 7.5 mg of ivabradine: median 4.9 [IQR 2.7 to 9.8]%; FMD after 4 weeks of ivabradine therapy: median 6.1 [IQR 4.3 to 8.2]%). No significant changes of the NMD were observed. In regression analysis, the heart rate and FMD did not correlated, irrespective of the ivabradine intake (r2 = 0.086). CONCLUSION: In conclusion, in our study heart rate reduction through ivabradine does not improve the endothelial function in patients with a stable coronary heart disease. Moreover, we found no correlation between the heart rate and the endothelial function.

Echocardiographic follow-up of patients with systemic sclerosis by 2D speckle tracking echocardiography of the left ventricle.

BACKGROUND: Subclinical myocardial involvement is common in systemic sclerosis (SSc) and associated with poor prognosis. Early detection, particularly during follow-up, is important. Two-dimensional speckle tracking echocardiography (STE) has already been shown to detect early left ventricular systolic impairment in SSc patients with advanced disease. The aim of this study was to assess the ability of STE to diagnose changes in left ventricular function in patients with SSc with preserved LV ejection fraction (LVEF) and normal pulmonary pressure over time. METHODS: This single-center pilot study included nineteen SSc patients without pulmonary hypertension and preserved LVEF (55.2 ± 10.8 years, 13 women, mean modified Rodnan Skin Score of 8.2 ± 6.5, median disease duration 6 ± 4.5 years). We performed STE at baseline and after two years (mean 756.6 ± 8.8 days). Pulmonary hypertension was ruled out in all patients by right heart catheterization (average mean PAP 17.7 ± 3.5 mmHg). RESULTS: The LVEF remained unchanged (63.3 ± 4.2% vs. 63.2 ± 5.0%, P = ns), but the global longitudinal peak systolic strain of the left ventricle was significantly lower: baseline -22.0 ± 2.3% vs. follow-up -20.8 ± 2.1% (P = 0.04). The regional analysis showed a heterogeneous distribution of segmental systolic dysfunction that did not match any particular coronary artery distribution. In contrast, the LV diastolic function remained stable during follow-up. CONCLUSION: STE might be a sensititive and valuable method to detect early LV systolic impairment in patients with SSc and preserved LVEF during two years. Prospective evaluations are needed for prognostic implications of these changes.

Increased longitudinal contractility and diastolic function at rest in well-trained amateur Marathon runners: a speckle tracking echocardiography study.

BACKGROUND: Regular physical activity reduces cardiovascular risk. There is concern that Marathon running might acutely damage the heart. It is unknown to what extent intensive physical endurance activity influences the cardiac mechanics at resting condition. METHODS: Eighty-four amateur marathon runners (43 women and 41 men) from Berlin-Brandenburg area who had completed at least one marathon previously underwent clinical examination and echocardiography at least 10 days before the Berlin Marathon at rest. Standard transthoracic echocardiography and 2D strain and strain rate analysis were performed. The 2D Strain and strain rate values were compared to previous published data of healthy untrained individuals. RESULTS: The average global longitudinal peak systolic strain of the left ventricle was -23 +/- 2% with peak systolic strain rate -1.39 +/- 0.21/s, early diastolic strain rate 2.0 +/- 0.40/s and late diastolic strain rate 1.21 +/- 0.31/s. These values are significantly higher compared to the previous published values of normal age-adjusted individuals. In addition, no age-related decline of longitudinal contractility in well-trained athletes was observed. CONCLUSIONS: There is increased overall longitudinal myocardial contractility at rest in experienced endurance athletes compared to the published normal values in the literature indicating a preserved and even supra-normal contractility in the athletes. There is no age dependent decline of the longitudinal 2D Strain values. This underlines the beneficial effects of regular physical exercise even in advanced age.

Long-term Doppler hemodynamics and effective orifice areas of Edwards SAPIEN and medtronic CoreValve prostheses after TAVI.

BACKGROUND: Although initial hemodynamics of percutaneously implanted aortic bioprostheses compare favorably to surgically implanted valves, the durability of the flow characteristics remains unknown. As biological prostheses are at potential risk for early degeneration, the aim of our study was to compare Doppler hemodynamics and effective orifice area (EOA) directly after and at least 1 year after valve implantation. METHODS: In this monocentric, prospective study, we determined peak velocity, peak and mean systolic gradients, and EOA by echocardiography in 75 patients (Edwards SAPIEN, n = 20; CoreValve, n = 55) 1 week (median 7 ± 25 days) and 1 year (median 378 ± 157 days, maximum 1034 days) after transcatheter aortic valve implantation (TAVI). RESULTS: After 12 months, Doppler performance of the aortic valve prostheses remained unchanged. The peak instantaneous velocity was 1.9 ± 0.4 m/s directly after TAVI versus 1.8 ± 0.5 m/s (P = ns) at follow-up, with a mean gradient of 8.5 ± 3.7 mmHg and 8.1 ± 4.2 (P = ns), respectively. Interestingly, the degree of mitral regurgitation (MR) decreased significantly (P = 0.007) over time, and the severity of aortic regurgitation (AR) remained unchanged during follow-up (P = ns). CONCLUSION: For at least 1 year after TAVI, the excellent Doppler hemodynamics and EOA are preserved in transcatheter aortic valve prostheses, and the severity of MR decreased significantly. In addition, we found no evidence of early valve deterioration or progression of AR.

Rapid binding of electrostatically stabilized iron oxide nanoparticles to THP-1 monocytic cells via interaction with glycosaminoglycans.

Magnetic resonance imaging (MRI) with contrast agents that target specific inflammatory components of atherosclerotic lesions has the potential to emerge as promising diagnostic modality for detecting unstable plaques. Since a high content of macrophages and alterations of the extracellular matrix are hallmarks of plaque instability, these structures represent attractive targets for new imaging modalities. In this study, we compared in vitro uptake and binding of electrostatically stabilized citrate-coated very small superparamagnetic iron oxide particles (VSOP) to THP-1 cells with sterically stabilized carboxydextran-coated Resovist(®). Uptake of VSOP in both THP-1 monocytic cells and THP-derived macrophages (THP-MΦ) was more efficient compared to Resovist(®) without inducing cytotoxicity or modifying normal cellular functions (no changes in levels of reactive oxygen species, caspase-3 activity, proliferation, cytokine production). Importantly, VSOP bound with high affinity to the cell surface and to apoptotic membrane vesicles. Inhibition of glycosaminoglycan (GAG) synthesis by glucose deprivation in THP-MΦ was associated with a significant reduction of VSOP attachment suggesting that the strong interaction of VSOP with the membranes of cells and apoptotic vesicles occurs via binding to negatively charged GAGs. These in vitro experiments show that VSOP-enhanced MRI may represent a new imaging approach for visualizing high-risk plaques on the basis of targeting pathologically increased GAGs or apoptotic membrane vesicles in atherosclerotic lesions. VSOP should be investigated further in appropriate in vivo experiments to characterize accumulation in unstable plaque.

Attenuation of early atherogenesis in low-density lipoprotein receptor-deficient mice by proteasome inhibition.

OBJECTIVE: Low and nontoxic proteasome inhibition has anti-inflammatory, antiproliferative, and antioxidative effects on vascular cells in vitro and in vivo. We hypothesized that low-dose inhibition of the proteasome could provide antiatherogenic protection. The present study investigated the effect of low-dose proteasome inhibition on early lesion formation in low-density lipoprotein receptor-deficient mice fed a Western-type diet. METHODS AND RESULTS: Male low-density lipoprotein receptor-deficient mice, 10 weeks old, were fed a Western-type diet for 6 weeks with intraperitoneal injections of bortezomib or solvent. Bortezomib was injected at a dose of 50 µg/kg body weight. Cholesterol plasma levels were not affected by bortezomib treatment. En face Oil Red O staining of aortae and aortic root cryosections demonstrated significant reduction of atherosclerotic lesion coverage in bortezomib-treated animals. Bortezomib significantly reduced vascular cellular adhesion molecule-1 expression and macrophage infiltration as shown by histological analysis. Bortezomib treatment resulted in a significant reduction of superoxide content, lipid peroxidation and protein oxidation products, serum levels of monocyte chemoattractant protein-1, and interleukin-6. Gene expression microarray analysis showed that expressional changes induced by Western-type diet were attenuated by treatment with low-dose bortezomib. CONCLUSIONS: Low-dose proteasome inhibition exerts antioxidative and anti-inflammatory effects and attenuates development of atherosclerotic lesions in low-density lipoprotein receptor-deficient mice.

Workload and usefulness of daily, centralized home monitoring for patients treated with CIEDs: results of the MoniC (Model Project Monitor Centre) prospective multicentre study.

AIM: Automated, daily Home Monitoring (HM) of pacemaker and implantable cardioverter-defibrillator (ICD) patients can improve patient care. Yet, HM introduction to routine clinical practice is challenged by resource allocation for regular HM data review. We tested the feasibility, safety, workload, and clinical usefulness of a centralized HM model consisting of one monitor centre and nine satellite clinics. METHODS AND RESULTS: Having no knowledge about patients' clinical data, a telemonitoring nurse (TN) and a supporting physician at the monitor centre screened and filtered HM data in 62 pacemaker and 59 ICD patients from nine satellite clinics for over 1 year. Basic screening of arrhythmic and technical events required 25.7 min (TN) and 0.7 min (physician) per working day, normalized for 100 patients monitored. Communication of relevant events to satellite clinics per email or phone required additional 4.3 min (TN) and 0.4 min (physician). Telemonitoring nurse also screened for abnormal developments in longitudinal data trends weekly for 3 months after implantation, and then monthly; one patient session lasted 4.0 ± 2.9 min. To handle transmission-gap notifications, TN needed additional 2.8 min daily. Satellite clinics received 231.3 observations from the monitor centre per 100 patients/year, which prompted 86.3 patient contacts or intensive HM screening periods by the satellite clinic itself (37.3% response rate), 51.7 extra follow-up controls (22.3%), and 30.1 clinical interventions (13.0%). CONCLUSION: Centralized HM was feasible, reliable, safe, and clinically useful. Basic screening and communication of relevant arrhythmic and technical events required a total of 30 min (TN) and 1.1 min (physician) daily per 100 patients monitored.

Left ventricular asynchrony in patients with right bundle branch block and normal ejection fraction.

AIMS: The role of right bundle branch block (RBBB) for the induction of left ventricular (LV) asynchrony is discussed controversially. The objective of this study was to assess presence and degree of LV asynchrony in patients with RBBB, left bundle branch block (LBBB), or left anterior hemiblock (LAH) and normal LV function. METHODS: We included 15 patients with RBBB, 13 patients with RBBB and concomitant LAH, 10 patients with pure LBBB, and 100 healthy controls into this study. All patients had normal LV function. Interventricular asynchrony was assessed as the difference of the right and LV ejection delay. Intraventricular delay was obtained by tissue synchronicity imaging-guided tissue Doppler imaging measurement. RESULTS: Interventricular and left intraventricular asynchrony were linked to the presence of an LBBB. No left intraventricular asynchrony was noted during pure RBBB; interventricular delays were negative (aortic flow preceding pulmonary flow) in the presence of RBBB. CONCLUSION: In patients with normal LV function, intraventricular asynchrony depends on the presence of an LBBB and interventricular asynchrony is inversed in the presence of RBBB.

Impact of remote telemedical management on mortality and hospitalizations in ambulatory patients with chronic heart failure: the telemedical interventional monitoring in heart failure study.

BACKGROUND: This study was designed to determine whether physician-led remote telemedical management (RTM) compared with usual care would result in reduced mortality in ambulatory patients with chronic heart failure (HF). METHODS AND RESULTS: We enrolled 710 stable chronic HF patients in New York Heart Association functional class II or III with a left ventricular ejection fraction ≤35% and a history of HF decompensation within the previous 2 years or with a left ventricular ejection fraction ≤25%. Patients were randomly assigned (1:1) to RTM or usual care. Remote telemedical management used portable devices for ECG, blood pressure, and body weight measurements connected to a personal digital assistant that sent automated encrypted transmission via cell phones to the telemedical centers. The primary end point was death from any cause. The first secondary end point was a composite of cardiovascular death and hospitalization for HF. Baseline characteristics were similar between the RTM (n=354) and control (n=356) groups. Of the patients assigned to RTM, 287 (81%) were at least 70% compliant with daily data transfers and no break for >30 days (except during hospitalizations). The median follow-up was 26 months (minimum 12), and was 99.9% complete. Compared with usual care, RTM had no significant effect on all-cause mortality (hazard ratio, 0.97; 95% confidence interval, 0.67 to 1.41; P=0.87) or on cardiovascular death or HF hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.67 to 1.19; P=0.44). CONCLUSIONS: In ambulatory patients with chronic HF, RTM compared with usual care was not associated with a reduction in all-cause mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00543881.

Pacing-induced cardiomyopathy in patients with right ventricular stimulation for >15 years.

AIMS: The prevalence of pacing-induced cardiomyopathy (PiCMP) has been reported to be 9% 1 year after implantation. As long-term data are sparse, the aim of our study was to evaluate the prevalence of PiCMP in a cohort of patients with at least 15 years of right ventricular (RV) pacing. METHODS AND RESULTS: Inclusion criteria were RV stimulation for at least 15 years due to atrioventricular block III° and absence of structural heart disease at the time of initial implantation. All patients were examined by echocardiography and spiroergometry. Pacing-induced cardiomyopathy was pre-defined as left ventricular (LV) ejection fraction (LVEF) ≤45%, dyskinesia during RV pacing and absence of other known causes of cardiomyopathy. Twenty-six patients from our outpatient department met the inclusion criteria. Pacing-induced cardiomyopathy was diagnosed in four patients (15.4%). Echocardiography showed significant LV remodelling in PiCMP patients [LVEF 41.0 ± 4.5%, LV end-diastolic diameter (LVEDD) 54.0 ± 2.7 mm] compared with patients with preserved LVEF (LVEF 61.2 ± 5.8%, P = 0.002, LVEDD 45.6 ± 4.0 mm, P= 0.004). There were no significant differences regarding age, gender, duration of RV pacing, heart rate, interventricular mechanical delay, QRS duration or prevalence of sinus rhythm, and arterial hypertension between both groups. The longest intraventricular delay was significantly shorter in patients with preserved LVEF (65.5 ± 43.0 ms) compared with PiCMP patients (112.5 ± 15.0 ms, P= 0.043). Exercise capacity and quality of life did not differ significantly between both groups. CONCLUSION: Considering the very long duration of RV stimulation in our study population (24.6 ± 6.6 years), the prevalence of PiCMP was remarkably low. Pacing-induced cardiomyopathy was associated with more pronounced intraventricular dyssynchrony.

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.