3D-Analysis of the Proximal Humeral Anatomy Before and After Stemless Shoulder Arthroplasty-A Prospective Case Series Study.

BACKGROUND: Stemless shoulder arthroplasty (SSA) is used to anatomically reconstruct proximal humerus geometry and preserve proximal humerus bone stock. The current literature lacks 3D-analysis of pre- and postoperative proximal humeral anatomy after SSA. The aim of this study was to prospectively analyze the humeral head anatomy using a computer-assisted topography mapping technique after SSA in relation to the preoperative status and the contralateral (not affected) side. METHODS: Twenty-nine patients (mean age: 63.5 ± 11.7 years) affected by primary shoulder osteoarthritis and treated with SSA were included. Preoperative and postoperative CT scans of the affected and contralateral sites were analyzed regarding joint geometry. Clinical outcome was assessed by Constant and Disabilities of the Arm, Shoulder and Hand (DASH) score shortly before and one year after surgery. RESULTS: Clinical outcome improved significantly. No correlation between clinical outcome and the evaluated anatomical parameters was found. There was a significant decrease of the humeral head height (p < 0.01) and radius (p = 0.03) in the preoperative versus the postoperative joint geometry. The comparison to the contralateral site showed also a significant decrease of the humeral head height (p < 0.01). All other parameters showed no significant differences. CONCLUSION: Proximal humeral anatomy can be almost anatomically reconstructed by SSA. Solely the humeral head height differs significantly to the preoperative as well as contralateral morphology.

Non-invasive determination of pressure recovery by cardiac MRI and echocardiography in patients with severe aortic stenosis: short and long-term outcome prediction.

OBJECTIVE: To assess the influence of pressure recovery (PR)-corrected haemodynamic parameters on outcome in patients with aortic stenosis. METHODS: Aortic stenosis severity parameters were corrected for PR (increase in static pressure due to decreasing dynamic pressure), assessed using transthoracic echocardiography (TTE) or cardiac magnetic resonance imaging (CMR), in patients with aortic stenosis. PR, indexed PR (iPR) and energy loss index (ELI) were determined. Factors that predicted all-cause mortality, and 9-month or 10-year New York Heart Association classification ≥2 were assessed using Cox proportional hazards regression. RESULTS: A total of 25 patients, aged 68 ± 10 years, were included. PR was 17 ± 6 mmHg using CMR, and CMR correlated with TTE measurements. PR correction using CMR data reduced the AS-severity classification in 12-20% of patients, and correction using TTE data reduced the AS-severity classification in 16% of patients. Age (Wald 4.774) was a statistically significant predictor of all-cause mortality; effective orifice area (Wald 3.753) and ELI (Wald 3.772) almost reached significance. CONCLUSIONS: PR determination may result in significant reclassification of aortic stenosis severity and may hold value in predicting all-cause mortality.

Association between Comorbidities and Progression of Transvalvular Pressure Gradients in Patients with Moderate and Severe Aortic Valve Stenosis.

BACKGROUND: Fast progression of the transaortic mean gradient (P mean) is relevant for clinical decision making of valve replacement in patients with moderate and severe aortic stenosis (AS) patients. However, there is currently little knowledge regarding the determinants affecting progression of transvalvular gradient in AS patients. METHODS: This monocentric retrospective study included consecutive patients presenting with at least two transthoracic echocardiography examinations covering a time interval of one year or more between April 2006 and February 2016 and diagnosed as moderate or severe aortic stenosis at the final echocardiographic examination. Laboratory parameters, medication, and prevalence of eight known cardiac comorbidities and risk factors (hypertension, diabetes, coronary heart disease, peripheral artery occlusive disease, cerebrovascular disease, renal dysfunction, body mass index ≥30 Kg/m2, and history of smoking) were analyzed. Patients were divided into slow (P mean < 5 mmHg/year) or fast (P mean ≥ 5 mmHg/year) progression groups. RESULTS: A total of 402 patients (mean age 78 ± 9.4 years, 58% males) were included in the study. Mean follow-up duration was 3.4 ± 1.9 years. The average number of cardiac comorbidities and risk factors was 3.1 ± 1.6. Average number of cardiac comorbidities and risk factors was higher in patients in slow progression group than in fast progression group (3.3 ± 1.5 vs 2.9 ± 1.7; P=0.036). Patients in slow progression group had more often coronary heart disease (49.2% vs 33.6%; P=0.003) compared to patients in fast progression group. LDL-cholesterol values were lower in the slow progression group (100 ± 32.6 mg/dl vs 110.8 ± 36.6 mg/dl; P=0.005). CONCLUSION: These findings suggest that disease progression of aortic valve stenosis is faster in patients with fewer cardiac comorbidities and risk factors, especially if they do not have coronary heart disease. Further prospective studies are warranted to investigate the outcome of patients with slow versus fast progression of transvalvular gradient with regards to comorbidities and risk factors.

Myocardial Fibrosis Predicts 10-Year Survival in Patients Undergoing Aortic Valve Replacement.

Background Long-term data on evolution and clinical impact of myocardial fibrosis in valvular heart disease are scarce. Methods and Results In this 10 years' extension of a prospective study in patients undergoing conventional aortic valve replacement because of symptomatic severe aortic valve stenosis, the impact of myocardial replacement fibrosis (MRF) on long-term outcome was assessed. Endomyocardial biopsies were acquired during aortic valve replacement in 58 consecutive patients. MRF was graded using the calculated percentage area of fibrosis and patients categorized as severe (n=21), mild (n=15), and no fibrosis (n=22). Echocardiography including strain imaging, as well as cardiovascular magnetic resonance, to assess late gadolinium enhancement was performed at baseline, 1, and 10 years after aortic valve replacement. Death of any cause occurred in 21 patients (38.9%): 3 (14.3%) in the group without MRF, 6 (42.9%) in the mild MRF group, and 12 (63.2%) in the severe MRF group ( P=0.006), resulting in the lowest cumulative survival for patients with severe MRF (log-rank P=0.003). In the group without MRF, none died of cardiovascular cause. MRF was found to be an independent predictor of survival (hazard ratio, 1.271; 95% CI, 1.032-1.564; P=0.024). Conclusions This 10-year follow-up study underlines the profound impact of replacement fibrosis with regard to cardiac and all-cause mortality in patients undergoing aortic valve replacement for severe aortic valve stenosis. Integrating cardiovascular magnetic resonance and echocardiographic functional imaging beyond ejection fraction quantification could help in clinical decision making to stratify patient prognosis with regard to myocardial longitudinal function and prevalence of replacement fibrosis.

Reverse shoulder arthroplasty: the role of physical therapy on the clinical outcome in the mid-term to long-term follow-up.

INTRODUCTION: Reverse shoulder arthroplasty shifts the rotational center of the shoulder joint caudally and medially to restore shoulder function in a rotator cuff deficient shoulder. Despite promising results in early- and mid-term follow-up, long-term loss in shoulder function has been described in the literature. A lack of exercise in elderly patients may be one reason for this loss in function. This study examines the functional benefits of physical therapy in the mid-term to long-term follow-up regarding the subjective and objective shoulder function. MATERIALS AND METHODS: Twenty patients with a mean age of 73 years were included in this series. The study was performed as a single-center, prospective study. Initial indications for reverse shoulder arthroplasty were cuff tear arthropathy, failed anatomical shoulder arthroplasty, and fracture sequelae. The patients were clinically examined at a mean follow-up of 62 months using the Constant score (CS) and the DASH score for the operated and the non-operated shoulder. They were reevaluated using the same scores following a standardized physical therapy program of 6 weeks' duration. RESULTS: The mean CS as well as the mean age- and gender-adjusted CS of the affected shoulder improved significantly from 53.5 to 59.3 points, and 72.7-80.8%, respectively. The subcategories activities of daily living (ADL) and range of motion (ROM) of the CS improved significantly, whereas no significant improvement was observed for the subcategories pain and strength. Evaluating the contralateral shoulder, no significant change was observed for the age- and gender-adjusted CS and the CS as well as its subcategories. We found no significant difference in the CS comparing the different etiologies prior to physical therapy. DISCUSSION: Physical therapy plays an important role subsequent to reverse shoulder arthroplasty. It also has an effect in the mid-term to long-term follow-up regarding the range of motion as well as activities of daily living. However, physical therapy seems to have limited effect on the strength and the residual pain level. LEVEL OF EVIDENCE: Level III.

Value of low-dose dobutamine stress echocardiography on defining true severe low gradient aortic stenosis in patients with preserved left ventricular ejection fraction.

Low-dose dobutamine stress echocardiography (DSE) is a valuable tool to distinguish true-severe (TS) from pseudo-severe (PS) low gradient aortic valve stenosis (LGAS) in patients with reduced left ventricular ejection fraction (LVEF). However, only scanty studies reported the clinical utility of DSE in differentiating TS-LGAS patients with preserved LVEF. We investigated the clinical utility of DSE in LGAS patients with preserved LVEF and the echocardiographic determinants suggestive of TS-LGAS. 130 consecutive LGAS patients [indexed aortic valve area (AVA) ≤ 0.6cm2/m2 and mean trans-aortic pressure gradient (PGmean) < 40mmHg] with preserved (≥ 50%, n = 63) and reduced (< 50%, n = 67) LVEF were included. DSE defined TS-LGAS (projected AVA ≤ 1 cm2) in 61.2% patients with reduced LVEF and in 68.3% patients with preserved LVEF. Multivariate logistic regression analysis showed that baseline AVA was an independent determinant of TS-LGAS both in LVEF ≥ 50% (OR 0.45, P = 0.004) and LVEF < 50% groups (OR 0.55, P = 0.005). Reduced septal and lateral mitral annular plane systolic excursion (MAPSE, OR 0.72 and 0.75, P = 0.013 and 0.016) and septal TDI-s´ were significantly associated with TS-LGAS in patients with LVEF ≥ 50%. Higher systolic pulmonary artery pressure (SPAP, OR 1.43, P = 0.045) was associated with TS-LGAS in patients with LVEF < 50%. DSE is useful to define TS-LGAS also in patients with preserved LVEF. Lower baseline AVA values are linked with TS-LGAS in both patients with reduced and preserved LVEF. Reduced MAPSE and septal TDI-s´ are suggestive of TS-LGAS in patients with preserved LVEF, while higher SPAP is associated with TS-LGAS in patients with reduced LVEF.

Association and diagnostic utility of diastolic dysfunction and myocardial fibrosis in patients with Fabry disease.

Objectives: Current guidelines highlight important therapy implications of cardiac fibrosis in patients with Fabry disease (FD). However, association between morphological and functional impairments with cardiac fibrosis in hereditary cardiomyopathies remains elusive. We investigated the association between echocardiography-determined cardiac dysfunction and cardiac MRI (cMRI)-detected myocardial fibrosis (late gadolinium enhancement, LE) in patients with FD with preserved left ventricular ejection fraction (≥50%). Methods: 146 patients with FD (aged 39±14 years, 57 men) were analysed, all receiving echocardiography and cMRI within a 1 week interval. Longitudinal systolic strain (LS_sys), strain rate (LSr_sys) and diastolic strain rate (LSr_E/LSr_A) were assessed using speckle-tracking imaging. Receiver operating characteristic (ROC) analysis was performed to identify the diagnostic performance of various markers for LE. Results: LE was detected in 57 (39%) patients with FD. LV wall thickness, left atrial volume, septal E/e', diastolic dysfunction grade, global LS_sys and E/LSr_E, mid-lateral LS_sys and LSr_E, as well as N-terminal pro-brain natriuretic peptide were all associated with LE independent of age, sex, body mass index, New York Heart Association functional class and kidney function. In ROC curve analysis, septal E/e' performed best (area under the curve=0.86, 95% CI=0.79 to 0.92). Septal E/e'>14.8 was strongly associated with LE (specificity=97.8% and sensitivity=49.1%). In 9% of patients, localised LE was present even though no other cardiac or kidney abnormalities were detected. Conclusions: Echocardiography-derived diastolic dysfunction is closely linked to LE in FD. Septal E/e' ratio is the best echocardiographic marker suggestive of LE. Diastolic dysfunction is not a prerequisite for LE in FD, since LE can be detected in the absence of measurable cardiac functional impairments. Trial registration number: ClinicalTrials.gov Identifier (NCT03362164).

Reverse shoulder arthroplasty: the role of physical therapy on the clinical outcome in the mid-term to long-term follow-up.

INTRODUCTION: Reverse shoulder arthroplasty shifts the rotational center of the shoulder joint caudally and medially to restore shoulder function in a rotator cuff deficient shoulder. Despite promising results in early- and mid-term follow-up, long-term loss in shoulder function has been described in the literature. A lack of exercise in elderly patients may be one reason for this loss in function. This study examines the functional benefits of physical therapy in the mid-term to long-term follow-up regarding the subjective and objective shoulder function. MATERIALS AND METHODS: Twenty patients with a mean age of 73 years were included in this series. The study was performed as a single-center, prospective study. Initial indications for reverse shoulder arthroplasty were cuff tear arthropathy, failed anatomical shoulder arthroplasty, and fracture sequelae. The patients were clinically examined at a mean follow-up of 62 months using the Constant score (CS) and the DASH score for the operated and the non-operated shoulder. They were reevaluated using the same scores following a standardized physical therapy program of 6 weeks' duration. RESULTS: The mean CS as well as the mean age- and gender-adjusted CS of the affected shoulder improved significantly from 53.5 points to 59.3 points, and 72.7-80.8%, respectively. The subcategories activities of daily living and range of motion of the CS improved significantly, whereas no significant improvement was observed for the subcategories pain and strength. Evaluating the contralateral shoulder, no significant change was observed for the age- and gender-adjusted CS and the CS as well as its subcategories. We found no significant difference in the CS comparing the different etiologies prior to physical therapy. DISCUSSION: Physical therapy plays an important role subsequent to reverse shoulder arthroplasty. It also has an effect in the mid-term to long-term follow-up regarding the range of motion as well as activities of daily living. However, physical therapy seems to have limited effect on the strength and the residual pain level. LEVEL OF EVIDENCE: Level III.

Extent of size, shape and systolic variability of the left ventricular outflow tract in aortic stenosis determined by phase-contrast MRI.

PURPOSE: Left ventricular outflow tract (LVOT) dimensions are important for calculation of aortic valve areas and planning of valve repair. Mostly, LVOT areas are calculated from echocardiographic longitudinal measurements with the assumption of a round shape. Here, orthogonal phase contrast (PC) MRI with dynamic assessment of LVOT was compared to standard longitudinal cine MRI and 2D echocardiography. METHODS: In 19 patients with aortic stenosis (5 female; 69±10years), LVOT areas were determined on orthogonal PC images, either by planimetry (Aplan) or by two-diameter measurement (Aellip). Data were analyzed in early, middle and late systole (t1/t2/t3). Additionally, standard diameter-based calculation (A3CV) of LVOT on longitudinal three-chamber view (3CV) MRI images and 2D echocardiography was performed. RESULTS: Calculated PC LVOT areas strongly correlated to planimetry (r=0.95; p<0.001) with almost identical areas (Aplan 5.1±1.1cm2 vs. Aellip 5.3±1.0cm2). In PC changes of LVOT-eccentricity during systole were most pronounced in late systole (t1 vs. t3plan -7.4±18%). Cine 3CV calculation resulted in lower LVOT areas compared to Aplan (A3CV 3.7±0.9cm2; p<0.001), yet correlating to Aplan (r=0.66; p=0.002). 3CV LVOT areas correlated to echocardiography (r=0.56; p=0.014). CONCLUSIONS: Calculated LVOT areas seem to be sufficient for daily routine. Compared to the orthogonal view, standard long-axis 3CV underestimates the LVOT size and overestimates the systolic reduction of LVOT-size. Systolic changes are most pronounced in late systole.

Role of Global Longitudinal Strain in the Prediction of Outcome in Patients With Severe Aortic Valve Stenosis.

In the present study, we assessed the role of Global Longitudinal Strain (GLS) as a predictor of all-cause mortality in patients with severe aortic valve stenosis (AS), irrespective of their type of treatment. Data of 807 patients with AS receiving complete echocardiographic and clinical examination were retrospectively analyzed. Valve area <1 cm2 and sufficient image quality were inclusion criteria; patients with severe concomitant valvulopathy were excluded. Patients were grouped into treatment (aortic valve replacement [AVR]) and conservative (non-AVR) groups. Multivariable Cox analysis was used to assess predictors of all-cause mortality. Five hundred fourteen patients were included and 53.3% were of male gender. Mean age at inclusion was 76.4 ± 9.8 years; 326 received AVR. Death from any cause occurred in 72.9% of non-AVR group and 17.8% of AVR group (p <0.001). GLS (expressed as |%|) was found to be an independent predictor of all-cause mortality in non-AVR group (hazard ratio [HR] 0.933, 95% CI 0.854 to 0.987, p = 0.038). In patients receiving AVR, GLS and history of coronary artery bypass graft were found to be independent predictors of all-cause mortality (HR for GLS 0.912, 95% CI 0.730 to 0.999, p = 0.048; HR for coronary artery bypass graft 2.977, 95% CI 1.014 to 6.273, p = 0.013). In non-AVR patients, GLS <9.7% showed a higher 1- and 5-year mortality (log rank p values of 0.002 and 0.010, respectively). In conclusion, GLS is an independent predictor of all-cause mortality in severe AS, irrespective of their type of treatment. GLS <9.7% indicates a significantly higher 1- and 5-year mortality in non-AVR patients. Therefore, GLS should be regularly assessed for enhanced risk stratification and clinical decision-making.

Value of tissue Doppler-derived Tei index and two-dimensional speckle tracking imaging derived longitudinal strain on predicting outcome of patients with light-chain cardiac amyloidosis.

Prognosis of patients with light-chain cardiac amyloidosis (AL-CA) is poor. Speckle tracking imaging (STI) derived longitudinal deformation parameters and Doppler-derived left ventricular (LV) Tei index are valuable predictors of outcome in patients with AL-CA. We estimated the prognostic utility of Tei index and deformation parameters in 58 comprehensively phenotyped patients with AL-CA after a median follow-up of 365 days (quartiles 121, 365 days). The primary end point was all-cause mortality. 19 (33%) patients died during follow-up. Tei index (0.89 ± 0.29 vs. 0.61 ± 0.16, p < 0.001) and E to global early diastolic strain rate ratio (E/GLSRdias) were higher while global longitudinal systolic strain (GLSsys) was lower in non-survivors than in survivors (all p < 0.05). Tei index, NYHA functional class, GLSsys and E/GLSRdias were independent predictors of all-cause mortality risk, and Tei index ≥0.9 (HR 7.01, 95% CI 2.43-20.21, p < 0.001) was the best predictor of poor outcome. Combining Tei index and GLSsys yielded the best results on predicting death within 1 year (100% with Tei index ≥0.9 and GLSsys ≤13%) or survival (95% with Tei index ≤0.9 and GLSsys ≥13%). We conclude that 1-year mortality risk in AL-CA patients can be reliably predicted using Tei index or deformation parameters, with combined analysis offering best performance.

Impact of centrality on cooperative processes.

The solution of today's complex problems requires the grouping of task forces whose members are usually connected remotely over long physical distances and different time zones. Hence, understanding the effects of imposed communication patterns (i.e., who can communicate with whom) on group performance is important. Here we use an agent-based model to explore the influence of the betweenness centrality of the nodes on the time the group requires to find the global maxima of NK-fitness landscapes. The agents cooperate by broadcasting messages, informing on their fitness to their neighbors, and use this information to copy the more successful agents in their neighborhood. We find that for easy tasks (smooth landscapes), the topology of the communication network has no effect on the performance of the group, and that the more central nodes are the most likely to find the global maximum first. For difficult tasks (rugged landscapes), however, we find a positive correlation between the variance of the betweenness among the network nodes and the group performance. For these tasks, the performances of individual nodes are strongly influenced by the agents' dispositions to cooperate and by the particular realizations of the rugged landscapes.

Cardiac amyloidosis mimicking severe aortic valve stenosis - a case report demonstrating diagnostic pitfalls and role of dobutamine stress echocardiography.

BACKGROUND: Aortic valve stenosis is a common finding diagnosed with high sensitivity in transthoracic echocardiography, but the examiner often finds himself confronted with uncertain results in patients with moderate pressure gradients and concomitant systolic heart failure. While patients with true-severe low-gradient aortic valve stenosis with either reduced or preserved left ventricular systolic function are primarily candidates for valve replacement, there is a relevant proportion of patients with pseudo-severe aortic valve stenosis anticipated not to benefit but actually rather deteriorate by interventional therapy or surgery. CASE PRESENTATION: In this article we present a case report of a male patient with pseudo-severe aortic valve stenosis due to cardiac amyloidosis highlighting the diagnostic schedule. The patient underwent stress echocardiography because of discrepant findings in transthoracic echocardiography and cardiac catheterization regarding the severity of aortic valve stenosis. After evaluation of the results, it became clear that he had a need for optimum heart failure medication and implantation of a cardiac resynchronization therapy defibrillator. CONCLUSION: Due to the pitfalls in conventional as well as invasive diagnostics at rest, Stress echocardiography should be considered part of the standard optimum diagnostic spectrum in all unclear or borderline cases in order to confirm the correct diagnosis and constitute optimal therapy.

Echocardiographic Determinants of One-Year All-Cause Mortality in Patients With Chronic Heart Failure Complicated by Significant Functional Tricuspid Regurgitation.

BACKGROUND: Right ventricular (RV) dysfunction plays an important role in chronic heart failure (CHF). We evaluated the echocardiographic determinants of 1-year all-cause mortality in CHF patients with clinically relevant functional tricuspid regurgitation (TR). METHODS AND RESULTS: A total of 101 consecutive CHF patients (mean age 74 ± 10 years, 53% male) with moderate or severe functional TR were enrolled. Each patient underwent at least 2 echocardiography examinations in an interval of >6 months. Clinical follow-up was made after a median of 305 (interquartile range 164-365) days after the last echocardiography. The primary end point was all-cause mortality. Forty-two patients (42%) died during follow-up. Baseline right atrial (RA) area, TR volume increase and RV enlargement over time were significantly higher in nonsurvivors than survivors (all P < .05). Compared to baseline levels, systolic pulmonary artery pressure (sPAP) was significantly reduced in nonsurvivors during follow-up echocardiography (54 ± 19 vs 49 ± 21 mm Hg; P = .010), but significantly increased in survivors (48 ± 17 vs 54 ± 17 mm Hg; P = .001). Multivariable survival analysis suggested that baseline RA area ≥27 cm2 (hazard ratio [HR] 2.41, 95% confidence interval [CI] 1.21-4.80; P = .013), follow-up TR proximal isovelocity surface area regurgitant volume increase ≥15 mL (HR 2.27, 95% CI 1.20-4.31; P = .012), RV middle diameter increase ≥10 mm (HR 2.38, 95% CI 1.10-5.11; P = .027), and sPAP reduction ≥10 mm Hg (HR 3.04, 95% CI 1.51-6.13; P = .002) were determinants of 1-year all-cause mortality after the last echocardiography. Patients with 2 or 3 of these determinants were faced with significantly increased 1-year mortality (88% or 100%). CONCLUSIONS: Dynamic RV morphologic and functional changes during serial echocardiography are associated with significantly increased mortality risk in CHF patients with moderate or severe functional TR.

Systematic Echocardiographic Evaluation of Mitral Valve Regurgitation for Transcatheter Edge-to-Edge Repair.

In patients with relevant mitral regurgitation (MR), transcatheter edge-to-edge repair (also called MitraClip) provides an alternative treatment option especially for inoperable or high-risk patients. In preparation for the procedure, echocardiography is the method of choice for assessment of mitral valve (MV) morphology and function and thus provides important information if successful treatment of MR can be accomplished by MitraClip. This review article provides structured and detailed guidance how to systematically assess functional and degenerative MR and MV pathology by echocardiography in order to select eligible patients for this procedure. Furthermore, it highlights state-of-the-art echocardiographic methods and potential pitfalls in patient selection.

Prevalence of severe mitral regurgitation eligible for edge-to-edge mitral valve repair (MitraClip).

OBJECTIVES: We assessed the prevalence of moderately severe or severe mitral regurgitation (MR) justifying edge-to-edge mitral valve (MV) repair (MitraClip(®)) in patients attending the University Hospital Wuerzburg, a tertiary care centre located in Wuerzburg, Germany. BACKGROUND: Transcatheter edge-to-edge MV repair of advanced MR is a non-surgical treatment option in inoperable and high-risk patients. It is unknown how many patients are potentially eligible for MitraClip(®) since several anatomical prerequisites of the MV apparatus have to be met for optimal treatment results. METHODS: Using a novel clinical data warehouse we searched for all patients attached to our Department of Internal Medicine from 01/2008 to 01/2012 with moderately severe or severe MR and aged ≥18 years. The current status of their treatment regime and eligibility for MitraClip(®) was assessed and re-evaluated according to current guidelines and echocardiographic criteria. RESULTS: The search of electronic medical records amongst 43,690 patients employed an innovative validated text extraction method and identified 331 patients with moderately severe or severe MR who had undergone echocardiographic assessment at our institution. Of these, 125 (38 %) received MV surgery and 206 (62 %) medical therapy only. Most patients not undergoing surgery had secondary MR (70 %). After evaluation of medical and echocardiographic data of medically treated patients (n = 206), 81 (39 %) were potential candidates for MitraClip(®) therapy, and 90 (44 %) died during the median follow-up time of 23 months. CONCLUSION: A large fraction of patients with moderately severe or severe MR but not operated was detected. Medically treated patients had a bad prognosis and about 40 % of them were potential candidates for MitraClip(®) therapy.

The septal bulge--an early echocardiographic sign in hypertensive heart disease.

Patients in the early stage of hypertensive heart disease tend to have normal echocardiographic findings. The aim of this study was to investigate whether pathology-specific echocardiographic morphologic and functional parameters can help to detect subclinical hypertensive heart disease. One hundred ten consecutive patients without a history and medication for arterial hypertension (AH) or other cardiac diseases were enrolled. Standard echocardiography and two-dimensional speckle-tracking-imaging analysis were performed. Resting blood pressure (BP) measurement, cycle ergometer test (CET), and 24-hour ambulatory BP monitoring (ABPM) were conducted. Patients were referred to "septal bulge (SB)" group (basal-septal wall thickness ≥ 2 mm thicker than mid-septal wall thickness) or "no-SB" group. Echocardiographic SB was found in 48 (43.6%) of 110 patients. In this SB group, 38 (79.2%) patients showed AH either by CET or ABPM. In contrast, in the no-SB group (n = 62), 59 (95.2%) patients had no positive test for AH by CET or ABPM. When AH was solely defined by resting BP, SB was a reasonable predictive sign for AH (sensitivity 73%, specificity 76%). However, when AH was confirmed by CET or ABPM the echocardiographic SB strongly predicted clinical AH (sensitivity 93%, specificity 86%). In addition, regional myocardial deformation of the basal-septum in SB group was significantly lower than in no-SB group (14 ± 4% vs. 17 ± 4%; P < .001). In conclusion, SB is a morphologic echocardiographic sign for early hypertensive heart disease. Sophisticated BP evaluation including resting BP, ABPM, and CET should be performed in all patients with an accidental finding of a SB in echocardiography.

Cardiac RKIP induces a beneficial ß-adrenoceptor-dependent positive inotropy.

In heart failure therapy, it is generally assumed that attempts to produce a long-term increase in cardiac contractile force are almost always accompanied by structural and functional damage. Here we show that modest overexpression of the Raf kinase inhibitor protein (RKIP), encoded by Pebp1 in mice, produces a well-tolerated, persistent increase in cardiac contractility that is mediated by the ß1-adrenoceptor (ß1AR). This result is unexpected, as ß1AR activation, a major driver of cardiac contractility, usually has long-term adverse effects. RKIP overexpression achieves this tolerance via simultaneous activation of the ß2AR subtype. Analogously, RKIP deficiency exaggerates pressure overload-induced cardiac failure. We find that RKIP expression is upregulated in mouse and human heart failure, indicative of an adaptive role for RKIP. Pebp1 gene transfer in a mouse model of heart failure has beneficial effects, suggesting a new therapeutic strategy for heart failure therapy.

Differences in natural history of low- and high-gradient aortic stenosis from nonsevere to severe stage of the disease.

BACKGROUND: The aim of the present study was to assess and compare the disease progression of aortic stenosis (AS) subtypes from nonsevere to severe disease on the basis of measures of gradient and flow. METHODS: Seventy-seven patients with AS (mean aortic valve area, 1.3 ± 0.3 cm(2) at baseline) underwent echocardiographic examination, including two-dimensional speckle-tracking strain measurements. Patients were retrospectively grouped according to mean transvalvular pressure gradient (40 mm Hg) into low-gradient (LG/AS) and high-gradient (HG/AS) groups. The LG/AS group was further subdivided into low-flow (LF/LG; i.e., stroke volume index < 35 mL/m(2)) and normal-flow (NF/LG) groups. For subanalysis, the LF/LG group was split into two groups: "paradoxical" (P-LF/LG; ejection fraction > 50%) and "classical" LF/LG (C-LF/LG; ejection fraction < 50%). Follow-up echocardiography was performed in patients with severe AS after 3.3 ± 1.7 years. Survival status was ascertained after 5.0 ± 2.0 years. RESULTS: Coronary artery disease was more frequent in LG/AS than HG/AS patients. Already at baseline, LF/LG patients showed reduced left ventricular global systolic strain and reduced systemic arterial compliance compared with HG/AS patients (HG/AS, 1.0 ± 0.4 mL · mm Hg-(1) · m(-2); NF/LG, 0.9 ± 0.2 mL · mm Hg-(1) · m(-2); LF/LG, 0.6 ± 0.2 mL · mm Hg(-1) · m(-2); P < .001). The initially elevated valvuloarterial impedance increased significantly more in LG/AS than in the other groups (HG/AS, 2.2 ± 0.9 mm Hg · mL-(1) · m(-2); NF/LG, 2.2 ± 0.5 mm Hg · mL-(1) · m(-2); LF/LG, 3.2 ± 0.8 mm Hg · mL(-1) · m-(2); P < .001), while aortic valve area decreased by 42% in HG/AS versus 34% in NF/LG and 32% in LF/LG (P < .001). At follow-up, global systolic strain was significantly reduced in C-LF/LG (7.7 ± 2.5 vs 13.5 ± 2.9 in P-LF/LG, P < .001). In P-LF/LG, mitral E/E' ratio increased significantly from 8.9 ± 4.0 to 26.4 ± 9.2 (P < .05). CONCLUSIONS: In patients with AS with high-gradient physiology, the valve constitutes the primary problem. By contrast, low-gradient AS is a systemic disease with valvular, vascular, and myocardial components, resulting in a slower progression of transvalvular gradient, but worse clinical outcome. In C-LF/LG, impaired systolic function leads to an LG flow pattern, whereas the pathophysiology in P-LF/LG is predominantly a diastolic dysfunction.