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Background The contribution of atrial and ventricular function in neurocardiogenic syncope (NCS) pathophysiology is elusive. Hypothesis We assessed the influence of echocardiographic properties to the age of presentation and NCS recurrences. Methods We assigned 124 patients with symptoms suggesting NCS, to those with syncope initiation at age 35 years (group B, n = 68). Echocardiographic indices were measured before head‐up tilt test (HUTT). Results A total of 55 had positive HUTT (44%) with a trend favoring group A (p = .08). Group A exhibited lower left atrial (LA) volume index (17 ± 6 vs. 22 ± 11 ml/m2, p = .015), higher LA ejection fraction (69 ± 10 vs. 63 ± 11%, p = .008), LA peak strain (reservoir phase 41 ± 13 vs. 31 ± 14%, p = .001, contraction phase 27 ± 11 vs. 15 ± 10%, p 3 recurrences (82.0% vs. 50.1%, p more...

Hypertrophic cardiomyopathy (HCM) represents one of the primary cardiomyopathies and may lead to heart failure and sudden cardiac death. Among various histologic features of the disease examined, assessment of myocardial fibrosis may offer valuable information, since it may be considered the common nominator for all HCM connected complications. Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) has emerged as the reference noninvasive method for visualizing and quantifying myocardial fibrosis in patients with HCM. T1 mapping, a promising new CMR technique, may provide an advantage over conventional LGE-CMR, by permitting a more valid quantification of diffuse fibrosis. On the other hand, echocardiography offers a significantly more portable, affordable, and easily accessible solution for the study of fibrosis. Various echocardiographic techniques ranging from integrated backscatter and contrast-enhanced ultrasound to two- (2D) or three-dimensional (3D) deformation and shear wave imaging may offer new insights into substrate characterization in HCM. The aim of this review is to describe thoroughly all different modalities that may be used in everyday clinical practice for HCM fibrosis evaluation (with special focus on echocardiographic techniques), to concisely present available evidence and to argue in favor of multi-modality imaging application. It is essential to understand that the role of various imaging modalities is not competitive but complementary, since the information provided by each one is necessary to illuminate the complex pathophysiologic pathways of HCM, offering a personalized approach and treatment in every patient. more...

Arterial stiffness is a strong predictor of death and cardiovascular (CV) events in hemodialysis patients. Only few studies tested interventions aiming to improve arterial stiffness in this population. This study examines the effect of dry-weight reduction with a standardized lung-ultrasound-guided strategy on ambulatory aortic blood pressure (BP) and arterial stiffness parameters in hemodialysis. Seventy-one clinically euvolemic hemodialysis patients with hypertension, were included in this single-blind randomized clinical-trial. Patients were randomized in the active group (n = 35), following dry-weight reduction guided by the total number of US-B lines before a mid-week dialysis session and the control group (n = 36), following standard treatment. Patients underwent office evaluation of arterial stiffness and 48-h ABPM to capture ambulatory central systolic (cSBP) and diastolic BP (cDBP) and arterial stiffness indexes at baseline and after 8-weeks. US-B lines decreased in the active and slightly increased in the control group (p more...

Aims We aimed at directly comparing three-dimensional (3D) and two-dimensional (2D) deformation parameters in hypertrophic hearts and depict which may best reflect underlying fibrosis in hypertrophic cardiomyopathy (HCM), defined by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR). Methods and results We included 40 HCM [54.1 ± 14.3 years, 82.5% male, maximum wall thickness (MWT) 19.3 ± 4.8 mm] and 15 hypertensive (HTN) patients showing myocardial hypertrophy (58.1 ± 15.6 years, 80% male, MWT 12.8 ± 1.4 mm) who have consecutively undergone 2D-, 3D-speckle tracking echocardiography and LGE CMR. Deformation parameters (2D and 3D) presented overall poor to moderate correlations, with 3D_longitudinal strain (LS) and 3D_circumferential strain (CS) values being constantly higher compared to 2D derivatives. By regression analysis, hypertrophy substrate (HCM vs. hypertension) and hypertrophy magnitude were the parameters to influence 2D–3D LS and CS strain correlations (R2 = 0.66, P Conclusions In hypertrophic hearts, 2D and 3D deformation parameters are not interchangeable, showing modest correlations. Thickness, substrate, and tracking algorithm calculating assumptions seem to induce this variability. Nevertheless, among HCM patients 2D_peak segmental longitudinal strain remains the best strain parameter for tissue characterization and fibrosis detection. more...

Background Left atrial (LA) form and function has been the focus of extensive research in heart failure with reduced ejection fraction (HFrEF). The LA coupling index (LACI, see Picture 1 for definition) and the LA function Index (LAFI) have both been proposed as potent predictors of morbidity and mortality in HFrEF. Albeit promising, both parameters have drawbacks that could limit their usefulness in clinical settings - LACI can only be measured during sinus rhythm (SR), while LAFI calculation is arguably more involved. A side-by-side comparison of the two indices has not yet been performed. Purpose Investigate and compare the feasibility and efficacy of using LACI and LAFI as prognostic factors in HFrEF. Methods HFrEF patients that visited our outpatient HF clinic were invited to participate in the study. Clinical examination, 6-minute walk testing, and a full echocardiographic study were performed, the latter enabling quantification of LACI, LAFI, as well as most traditional echocardiographic predictors of HF prognosis (Picture 1). LACI and LAFI cut-offs of 6 and 25 respectively were defined in accordance with the relevant literature. Cox regression was performed to assess each parameter's correlation with risk of HF-related hospitalization and mortality over a 6-month follow-up period. Results In the end, 63 patients were included in the study (aged 69.3±9.7 years, 84% male). LACI could not be measured in 19 patients due to atrial tachycardia. The median LACI was 6.2 (8.7) while the median LAFI of the entire sample was 24.8 (44.5). LACI and LAFI correlated strongly (r=−0.813, p Conclusions The collinearity detected between LACI and LAFI indicate that both quantify similar aspects of left atrial (dys)function. That said, neither index had significant capability to predict hospitalization or death in our sample of HFrEF patients. Although a non-significant trend for higher LACI in patients with poorer prognosis was detected in our sample, it was also incalculable in 30% of patients, who were not in SR during echocardiography. Extended follow-up of an expanded sample size will enable more refined investigation of LACI's and LAFI's prognostic capacity. Funding Acknowledgement Type of funding sources: None. Hospitalization Cox regression resultsLACI and LAFI survival curves more...

Background Diastolic function assessment in patients with hypertrophic hearts and preserved ejection fraction (EF) is a rather challenging task. Combined plotting of deformation parameters against other indices, especially left ventricular (LV) volume, may reflect diastolic function components of the hypertrophic myocardium. Purpose Aim of this study was i) to apply strain-volume loops (SVLs) in hypertrophic cardiomyopathy (HCM) patients based on simultaneous frame-by-frame strain and volume changes' recordings acquired by means of three-dimensional (3D) speckle tracking imaging and ii) to investigate potential correlations between these loops, traditional diastolic function indices and phenotypic features of HCM (thickness, obstruction and fibrosis) that may also reflect myocardial “stiffness”. Methods We included 40 HCM patients (54.1±14.3 years, 82.5% male, maximum wall thickness 19.3±4.8mm) who have consecutively undergone 3D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). Values of 3D strain were plotted vs. volume for each frame to build an SVL. Peak of radial, longitudinal and circumferential systolic strain (Rsp, Lsp, and Csp, respectively), systolic slopes of the loops (RsSl, LsSl, CsSl), strain to end-diastolic volume (EDV) ratios (Rs/V, Ls/V, Cs/V) as well as the extent of systolic-diastolic uncoupling (difference between systolic and diastolic strain for the same volume) (panel A) were computed for the analysis. Left atrial volume index (LAVI), E/E' and tricuspid regurgitation velocity (TRvel) were measured to define diastolic dysfunction (DD) stage. Burden of fibrosis was evaluated by LGE extent in CMR slices. Results All HCM patients had preserved EF (60.5±5,7%), while 16 (40%) had LV outflow tract obstruction (LVOTO>30 mm Hg at rest). Mean LV mass index was 78.9±14.5 g (evaluated by 3D echocardiography). LGE was observed in 23 patients (57.5%) occupying 5.2±4.5% of LV mass. Concerning SVLs the following values were recorded for radial (Rsp 30.8±9.8%, RsSl 0.4±0.13 and Rs/V 0.25±0.09), longitudinal (Lsp −9.4±3.7%, LsSl 0.12±0.06 and Ls/V 0.08±0.04) and circumferential deformation (Csp −14.2±3.5%, CsSl 0.18±0.05 and Cs/V 0.11±0.03). Traditional isolated diastolic indices (E/E', LAVI, TRvel and DD stage) did not present significant correlations with SVL parameters or HCM phenotypic features. However, potentially “stiffer” hearts (combination of increased LVMI and fibrosis) presented a leftward transition of longitudinal SVLs, which also became wider (greater uncoupling) (panel B). Conclusions Traditional diastolic indices show modest only correlations with SVLs or HCM phenotypic characteristics, necessitating new approaches to DD of HCM patients. SVLs seem to be a promising-innovative tool for indirect assessment of myocardial “stiffness” and diastolic function. Funding Acknowledgement Type of funding sources: None. Figure 1 more...

Background: Pacing the right heart has been shown to induce reversible conduction delay and subse­quent asymmetric remodeling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore the aim of this study was to develop a more feasible and easy-to-use animal model in sheep. Methods: Dual-chamber (DDD) pacemakers with epicardial leads on the right atrium and right ven­tricular free wall were implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm. Results: DDD pacing acutely induced a left bundle branch block (LBBB) — like pattern with almost doubling in QRS width and the appearance of a septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodeling (confirmed with histology) with septal wall thinning (–30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (–31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD pacing decreased immediately work in the septum and increased it in the lateral wall (–69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (–27% and -25%, respectively, p < 0.05). Conclusions: This study presents the development a new sheep model with an asymmetrically remod­eled LV. Simple pacemaker programing allows direct modulation of regional myocardial function and work. This animal model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodeling. more...

AimWe aimed to investigate the main anthropometric, cardiorespiratory and haematological factors that can determine marathon race performance in marathon runners.MethodsForty-five marathon runners (36 males, age: 42 ± 10 years) were examined during the training period for a marathon race. Assessment of training characteristics, anthropometric measurements, including height, body weight (n = 45) and body fat percentage (BF%) (n = 33), echocardiographic study (n = 45), cardiopulmonary exercise testing using treadmill ergometer (n = 33) and blood test (n = 24) were performed. We evaluated the relationships of these measurements with the personal best marathon race time (MRT) within a time frame of one year before or after the evaluation of each athlete.ResultsThe training age regarding long-distance running was 9 ± 7 years. Training volume was 70 (50–175) km/week. MRT was 4:02:53 ± 00:50:20 h. The MRT was positively associated with BF% (r = 0.587, p = 0.001). Among echocardiographic parameters, MRT correlated negatively with right ventricular end-diastolic area (RVEDA) (r = −0.716, p < 0.001). RVEDA was the only independent echocardiographic predictor of MRT. With regard to respiratory parameters, MRT correlated negatively with maximum minute ventilation indexed to body surface area (VEmax/BSA) (r = −0.509, p = 0.003). Among parameters of blood test, MRT correlated negatively with haemoglobin concentration (r = −0.471, p = 0.027) and estimated haemoglobin mass (Hbmass) (r = −0.680, p = 0.002). After performing multivariate linear regression analysis with MRT as dependent variable and BF% (standardised β = 0.501, p = 0.021), RVEDA (standardised β = −0.633, p = 0.003), VEmax/BSA (standardised β = 0.266, p = 0.303) and Hbmass (standardised β = −0.308, p = 0.066) as independent variables, only BF% and RVEDA were significant independent predictors of MRT (adjusted R2 = 0.796, p < 0.001 for the model).ConclusionsThe main physiological determinants of better marathon performance appear to be low BF% and RV enlargement. Upregulation of both maximum minute ventilation during exercise and haemoglobin mass may have a weaker effect to enhance marathon performance.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT04738877. more...

Although previous studies suggest that prolonged intense exercise such as marathon running transitorily alters cardiac function, there is little information regarding ultramarathon races. Aim of this study was to investigate the acute impact of ultra-endurance exercise (UEE) on heart, applying advanced strain imaging. Echocardiographic assessment was performed the day before and at the finish line of "Spartathlon": A 246 Km ultra-marathon running race. 2D speckle-tracking echocardiography was performed in all four chambers, evaluating longitudinal strain (LS) for both ventricles and atria. Peak strain values and temporal parameters adjusted for heart rate were extracted from the derived curves. Out of 60 participants initially screened, 27 athletes (19 male, age 45 ± 7 years) finished the race in 33:34:27(28:50:38-35:07:07) hours. Absolute values of right (RV) and left ventricular (LV) LS (RVLS -22.9 ± 3.6 pre- to -21.2 ± 3.0% post-, p=0.04 and LVLS -20.9 ± 2.3 pre- to -18.8 ± 2.0 post-, p=0.009) slightly decreased post-race, whereas atrial strain did not change. RV and LV LS decrease was caused mainly by strain impairment of basal regions with apical preservation. Inter-chamber relationships assessed through RV/LV, LV/LA, RV/RA and RA/LA peak values' ratios remained unchanged from pre to post-race. Finally, UEE caused an extension of the systolic phase of cardiac cycle with concomitant diastole reduction (p more...

There is little research about the effects of ultra-endurance exercise on arterial morphological and functional properties. The aim was to assess the acute changes of the carotid-femoral pulse wave velocity and carotid doppler-derived parameters following an ultra-marathon race as well as the intima-media thickness of the carotid artery in ultra-marathon runners. Twenty athletes were examined at baseline and within 10 mins after a 246 km running race. Measurements included carotid-femoral pulse wave velocity, peak-systolic and end-diastolic velocities of carotid artery blood flow, pulsatility and resistivity indices and blood biochemical parameters. The intima-media thickness of the right and left carotid artery was measured before the race. Arterial stiffness and carotid artery intima media thickness at rest remained within known normal limits. The ultra-marathon race significantly increased carotid-femoral pulse wave velocity by 22.6% and pulsatility index by 10.2%. There was a decrease in body weight by 3.35% and an increase of all biochemical markers of muscle damage after the race. Additionally, C-reactive protein was correlated with both pulsatility and resistivity indices post-race. This study shows that immediately after a 246 km ultra-marathon running race, acute increase of arterial stiffness and vascular resistance were evident. The carotid artery thickness of ultra-marathon runners was within normal range. more...

Background Catheter ablation has emerged as an effective therapy in patients with atrial fibrillation (AF). Despite high success rates of the method, there is still heterogeneity of outcomes and complications across Europe. A center's volume of AF ablations performed per year might also play an important role in the success rate of the procedure as compared to other confounding factors which may be different among centers (such as type of AF ablated, patient selection criteria, referral bias and/or ablation strategy). Purpose Aim of the study was to investigate differences in clinical outcomes and complication rates among European AF ablation centers related to the volume of ablations performed annually. Methods Data for this analysis were extracted from the European AF Ablation Long-Term Study, a prospective registry designed to describe the clinical epidemiology of patients undergoing AF ablation. Based on 33th and 67th percentiles of number of AF ablations performed, the participating centers were classified into high volume (HV) (≥180 procedures/year), medium volume (MV) ( Results A total of 91 centers in 26 European countries enrolled 3368 patients. There was a significantly higher reporting of cardiovascular complications in LV centers (5.2%), especially pericarditis and cardiac perforation, while the HV and MV centers reported cardiovascular complications in 3.0 and 4.3% of cases, respectively (p=0.039). Additionally, stroke incidence after ablation was significantly higher in LV centers (0.5% of cases vs 0% in HV and MV centers, p=0.008). One-year success after AF ablation ranged from 77.8% in HV vs 70.5% in LV vs 77.3% in MV centers (p Conclusions Low volume centers present slightly higher cardiovascular complications' and stroke incidence and a lower unadjusted success rate after AF ablation. On the other hand, adjusted overall complication and recurrence rates are non-significantly different among different volume centers, a fact reflecting inhomogeneity of patient and procedural profiles and a counterbalance between expertise and risk level among participating centers. Funding Acknowledgement Type of funding source: None more...

Aims The aim of the study was to investigate differences in clinical outcomes and complication rates among European atrial fibrillation (AF) ablation centres related to the volume of AF ablations performed. Methods and results Data for this analysis were extracted from the ESC EHRA EORP European AF Ablation Long-Term Study Registry. Based on 33rd and 67th percentiles of number of AF ablations performed, the participating centres were classified into high volume (HV) (≥ 180 procedures/year), medium volume (MV) ( Conclusion Low-volume centres tended to present slightly higher cardiovascular complications’ and stroke incidence and a lower unadjusted success rate after AF ablation, despite the fact that ablation procedures and patients were of lower risk compared with MV and HV centres. On the other hand, adjusted overall complication and recurrence rates were non-significantly different among different volume centres, a fact reflecting the heterogeneity of patient and procedural profiles, and a counterbalance between expertise and risk level among participating centres. more...

Background: To evaluate long-term clinical outcomes after treatment of complex bifurcation lesions with the AXXESS dedicated self-expanding biolimus A9-eluting bifurcation stent. Methods: Between 2004 and 2013, 123 patients with complex bifurcation lesions were treated in a single-center with the AXXESS stent in the proximal main vessel (MV) and additional drug-eluting stents in branches when required. Median follow-up was 5 years. Primary endpoint was the rate of major adverse cardiac events (MACE). Secondary endpoints included MACE components (cardiac death, non-periprocedural clinical myocardial infarction [MI], target lesion revascularization [TLR] and definite/probable stent thrombosis [ST]) as well as all-cause death, target vessel revascularization (TVR) and non-TVR. Results: During follow-up, 11 (8.9%) patients experienced a MACE, of whom 2 (1.6%) suffered cardiac death, 2 (1.6%) had a non-periprocedural clinical MI requiring TLR, and 7 (5.7%) underwent elective TLR. No definite/probable ST was observed. All-cause death occurred in 9 (7.3%) patients, TVR in 11 (8.9%) and non-TVR in 11 (8.9%). Patients treated for left main (LM) bifurcation lesions were more likely to experience MACE than non-LM bifurcation lesions (25% vs. 6.5%, p = 0.04). Conclusions: Percutaneous revascularization of complex bifurcation lesions with the AXXESS stent is safe and provides excellent long-term results, especially in non-LM lesions. more...

AIMS We aimed at investigating the relationship between segmental morphology [wall thickness (WT) and WT location (LT: base-mid-apex)], loading conditions and underlying pathological substrate [histology (H), hypertrophy vs. infiltration] with segmental longitudinal (SLS) and circumferential (SCS) strain in a group of patients with hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA). METHODS AND RESULTS We included 30 patients with biopsy-proven CA (65.4 ± 10.7 years, 66% male, 76.7% AL type) and 50 patients with HCM matched for maximum WT (60 ± 16 years, 80% male). SLS and SCS were assessed with speckle-tracking echocardiography in an 18-segment model of left ventricle, while morphological parameters were measured in short-axis cardiovascular magnetic resonance cine loops which corresponded with echo segments. In total, 1440 segments were evaluated of which 198 (36.7%) in CA and 252 (28%) in HCM had WT >12 mm (maximum WT 18.1 ± 3.7 mm in CA vs. 18.6 ± 4.1 in HCM, P = 0.59). SLS showed association with WT [beta 0.49, 95% confidence interval (CI) 0.37-0.6; P more...

Objectives The purpose of this study was to compare the accuracy of vendor-specific and independent strain analysis tools to detect regional myocardial function abnormality in a clinical setting. Background Speckle tracking echocardiography has been considered a promising tool for the quantitative assessment of regional myocardial function. However, the potential differences among speckle tracking software with regard to their accuracy in identifying regional abnormality has not been studied extensively. Methods Sixty-three subjects (5 healthy volunteers and 58 patients) were examined with 7 different ultrasound machines during 5 days. All patients had experienced a previous myocardial infarction, which was characterized by cardiac magnetic resonance with late gadolinium enhancement. Segmental peak systolic (PS), end-systolic (ES) and post-systolic strain (PSS) measurements were obtained with 6 vendor-specific software tools and 2 independent strain analysis tools. Strain parameters were compared between fully scarred and scar-free segments. Receiver-operating characteristic curves testing the ability of strain parameters and derived indexes to discriminate between these segments were compared among vendors. Results The average strain values calculated for normal segments ranged from −15.1% to −20.7% for PS, −14.9% to −20.6% for ES, and −16.1% to −21.4% for PSS. Significantly lower values of strain (p Conclusions The accuracy of identifying regional abnormality differs significantly among vendors. more...

Aim The investigation of the pathophysiological determinants of cardiac changes following ultra-long duration exercise. Methods Twenty-seven runners who finished a 246 km running race were examined both before and after the finish of the race. Examinations included echocardiography and measurement of body weight and blood biochemical parameters. Results Exercise increased left ventricular end-diastolic interventricular septum thickness (LVIVSd) ( p Conclusion The main cardiac effects of ultra-long duration exercise were the decrease in left ventricular end-diastolic dimensions and increase in left ventricular wall thickness, as well as minimal dilatation and alteration in systolic function of right ventricle, possibly due to the altered exercise-related right ventricular afterload. more...

Aims Investigating the acute impact of cardiac resynchronization therapy (CRT) on regional myocardial work distribution in the left ventricle (LV) and to which extent it is related to long-term reverse remodelling. Methods and results One hundred and thirty heart failure patients, referred for CRT implantation, were recruited in our prospective multicentre study. Regional myocardial work was calculated from non-invasive segmental stress–strain loop area before and immediately after CRT. The magnitude of volumetric reverse remodelling was determined from the change in LV end-systolic volume, 11 ± 2 months after implantation. CRT caused acute redistribution of myocardial work across the LV, with an increase in septal work, and decrease in LV lateral wall work (all P Conclusion The acute redistribution of regional myocardial work between the septal and lateral wall of the LV is an important determinant of reverse remodelling after CRT implantation. Our data suggest that the treatment of the loading imbalance should, therefore, be the main aim of CRT. more...

The aim of this study was to explore the association between mechanical dyssynchrony of the left ventricle before cardiac resynchronization therapy (CRT) and improvement of mitral regurgitation (MR) after CRT.MR is very frequent among patients with dilated cardiomyopathy and conduction delay.Echocardiograms (pre-CRT and 12 ± 3.8 months thereafter) of 314 patients with dilated cardiomyopathy and any degree of MR, who underwent CRT device implantation according to guidelines, were analyzed. Left ventricular (LV) mechanical dyssynchrony was assessed by apical rocking (ApRock) and septal flash (SF), while MR severity was graded from I to IV on the basis of vena contracta width, regurgitation jet size, and proximal isovelocity surface area.At baseline, 30% of patients presented with severe MR (grade III or IV). In 62% of patients, MR decreased after CRT, and these patients more frequently had left bundle branch block, had more severe MR, had more dilated left ventricles, had lower ejection fractions, and more often had ApRock and SF. Reverse remodeling was more frequent among patients with MR reduction (ΔLV end-systolic volume -35.5% ± 27.2% vs -4.1% ± 33.2%; P 0.001). In a multivariable logistic stepwise regression, only ApRock (odds ratio [OR]: 3.8; 95% CI: 1.7-8.5; P = 0.001), SF (OR: 3.6; 95% CI: 1.6-7.9; P = 0.002), and baseline MR (OR: 1.4; 95% CI: 1.0-1.9; P = 0.046) remained significantly associated with MR reduction.ApRock, SF, and severity of MR at baseline are strongly associated with MR reduction after CRT, while LV reverse remodeling is its underlying mechanism. Therefore, in patients with heart failure with LV dyssynchrony on optimal medical treatment, CRT should be the primary treatment attempt for relevant MR. more...

Introduction and purpose Hemodialysis patients have premature arterial stiffness, and the relationship between pulse wave velocity (PWV) and blood pressure (BP) may be different than in other hypertensives. Previous studies showed that when BP decrease is accompanied by PWV decrease the survival is improved. The aim of this study is to examine the prognostic significance of BP sensitivity of PWV for major cardiovascular outcomes and all-cause mortality in hemodialysis patients. Methods This is a prospective cohort study including 242 hemodialysis patients [age, 62.6±14.2 years; female, 91 (37.6%); hemodialysis vintage, 41.53±43.46]. All subjects underwent 48-hour-ABPM with Mobil-O-Graph-NG and followed-up for 33.17±19.68 months. The within-individual MBP-PWV association (MBP, dependent and PWV independent variable) was evaluated using the beta-coefficient value from simple linear regression analysis for each patient. The primary end-point was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary end-points were: (i) all-cause mortality; (ii) cardiovascular mortality; (iii) a combination of cardiovascular events. Results Patients who experienced the primary end-point during follow-up had significantly lower beta-coefficient levels (primary end-point: 19.877±3.975 vs 18.483±3.550, p=0.008). Higher quartiles of beta-coefficients (indicating dependency of PWV on MBP) were associated with higher cumulative freedom from the primary end-point (50.8%, 60.0%, 70.0% and 80.3% for quartiles 1 to 4 respectively; logrank-p=0.001), higher overall survival (60.7%, 61.7%, 73.3%, 86.9%; logrank-p=0.002) and higher cardiovascular survival (78.7%, 75.0%, 81.7%, 91.8% for quartiles 1 to 4; logrank-p=0.044). The future risk for the primary end-point, all-cause and cardiovascular mortality and the combined outcome was progressively increasing for lower quartiles of beta-coefficients (HR for all-cause mortality 3.395; 95% CI: 1.524–7.563, p=0.003 for quartile 1 vs quartile 4). Age (OR: 1.046, 95% CI: 1.016–1.077 per year increase, p=0.003) and 48h heart rate (OR: 0.949, 95% CI: 0.916–0.982 per bpm increase, p=0.003) were independently associated with weaker relationship between 48h-MBP and 48h-PWV. Conclusions Lower within-individual MBP-PWV association, based on AMBP recordings, is associated with higher risk of death and cardiovascular events in hemodialysis. These findings support that BP-independent arterial stiffness may be the underlying factor for adverse outcomes in these individuals. more...

Background In patients with dilated cardiomyopathy and left bundle branch block (LBBB), different regions of the left ventricle (LV) have been shown to perform different amounts of work. In this study, we investigate the acute impact of cardiac resynchronization therapy (CRT) on regional LV work distribution and its relation to long-term reverse-remodelling. Methods We recruited 130 heart failure patients, referred for CRT. Regional myocardial work was calculated from non-invasive echocardiographic segmental stress-strain-loop-area before and immediately after CRT. The magnitude of volumetric reverse-remodelling was determined from the change in LV end-systolic volume (ESV), 11±2 months after implantation. Characteristics of patients with the lowest and highest quartile of LV ESV reverse remodelling (ΔLV ESV −48%) were compared. Results Before CRT, myocardial work showed significant differences among the walls of the LV (Figure 1A). CRT caused an acute re-distribution of myocardial work, on average with most increase in the septum and most decrease laterally (all walls p Figure 1 Conclusions The acute re-distribution of regional myocardial work between the septal and lateral wall of the left ventricle is the main determinant of long term reverse-remodelling after CRT-implantation. Our data suggest that modification of regional loading is the mode of action of CRT treatment. more...

Background Pressure-strain-loops (PSL) have been suggested as surrogate parameter of regional myocardial work. However, in left ventricles (LV) with inhomogeneous remodelling, e.g. due to left bundle branch block (LBBB), wall stress may be unevenly distributed. Stress-strain loops (SSL) include information on both regional wall thickness and curvature, and may therefore provide a better surrogate. Study plan We therefore compared the correlation of segmental myocardial work estimated through both PSL and SSL to segmental myocardial glucose metabolism as a gold standard, in an animal model of pacing-induced LV remodelling. Methods Twelve sheep developed LV dilatation, thinned septum and thickened lateral wall, due to eight weeks of rapid right-atrial and right-ventricular free wall (DDD) pacing (at 180 bpm), causing a LBBB-like dyssynchrony. Invasive LV pressure and echocardiographic speckle tracking based circumferential strain were used to construct PSL. SSL were calculated by considering in addition dynamic changes in segmental myocardial wall thickness and curvature using the formula of Laplace. 18F-fluorodeoxyglucose (FDG)-uptake was measured by positron emission tomography (PET) in absolute values as standardised uptake ratio (SUR). Spatial resolution of PET was improved by ECG- and breathing-gating and using anatomical priors. All imaging was performed during dyssynchronous DDD-pacing and synchronous AAI-pacing (right-atrial pacing only), at baseline (n=3 animals), and after eight weeks of pacing induced remodelling (n=12 animals). Results Both at baseline (Fig. A+B) and after 8 weeks (Fig. D+E), switching between AAI and DDD-pacing caused an acute re-distribution of regional myocardial work as measured by both PSL and SSL. In contrast to PSL, however, SSL identified more regional differences among walls in remodelled hearts and showed clearer regional changes when switching between AAI and DDD-pacing. The correlation between regional work, assessed by PSL and SSL, and metabolism by PET, was comparable at baseline (r=0.65 and r=0.64, respectively) (Fig. C). In remodelled hearts after 8 weeks, however, the correlation of regional work assessed by SSL and glucose uptake by PET was significantly higher compared to PSL (r=0.73 vs. r=0.59, respectively; p Conclusions Regional myocardial work assessed by stress-strain loops correlates significantly better to regional metabolism as measured by PET glucose uptake, particularly after remodelling. Our findings therefore suggest that integrating information on wall thickness and curvature is essential for the reliable assessment of regional myocardial work, especially in dyssynchronous and remodelled left ventricles. more...

Background Catheter ablation has emerged as an effective therapy in patients with symptomatic and drug refractory atrial fibrillation (AF). Despite high success rates of the method, there is still heterogeneity of outcomes and complication rate across Europe. The impact of the annual procedural volume per center on success and complication rate of AF ablation, based on real-life data, has not been addressed till now. Purpose The aim of the study was to investigate if center AF ablation volume might be associated with one-year success or complication rate after the procedure. Methods Data for this analysis were extracted from the European AF Ablation Long-Term Study, a prospective registry designed to describe the clinical epidemiology of patients undergoing AF ablation. Based on 25th and 75th percentiles of AF ablation numbers performed, the participating centers were classified into high volume (HV) (≥250 procedures/year), medium volume (MV) ( Results A total of 91 centers in 26 European countries enrolled 3368 patients. There was a significantly higher reporting of cardiovascular complications in LV centers (5.2%), especially pericarditis (0.6%) and cardiac perforation (1.4%), while the HV and MV centers reported cardiovascular complications in 3.0 and 4.3% of cases, respectively (p=0.039). Additionally, stroke incidence after ablation was significantly higher in LV centers (0.5% of cases vs 0% in HV and MV centers, p=0.008). Kaplan-Meier survival analysis based on adjusted data of all complications demonstrated, however, that there was not a significant difference in complication rate according to volume's center (p=0.402, Figure A). One-year success after AF ablation ranged from 77.8% in HV vs 70.5% in LV vs 77.3% in MV centers (p Conclusions Despite the notion that “the higher, the better”, our results suggest that AF ablation is a safe procedure with high success rates in all European centers, independent of the AF ablation procedural volume. Differences in patients and procedural characteristics may justify the equality of complication and recurrence rate among centers, since expertise level counterbalances the risk of each case. more...

Introduction and purpose Left ventricular hypertrophy and dysfunction is tightly associated with adverse outcome in hemodialysis. Hypertension and increased preload due to hypervolemia are major factors for these cardiac anomalies in hemodialysis. This study examined the effect of lung-ultrasound-guided dry-weight reduction on echocardiographic indices of left and right cardiac size, systolic and diastolic function in hypertensive hemodialysis patients. Methods This pilot, single-blind trial randomised 71 clinically euvolemic hypertensive hemodialysis patients in an active group (n=35), following a strategy for dry-weight reduction guided by the total number of US-B lines (US-B lines score) prior to a mid-week dialysis session, and a control group (n=36), following standard-of-care treatment. Among others, patients underwent two-dimensional and tissue-Doppler echocardiographic (TDI) at baseline and after 8-weeks. Results Overall, 19 (54.3%) patients in the active and 5 (13.9%) in the control group had UF intensification (p Conclusions A lung-ultrasound-guided strategy for dry-weight reduction can effectively reduce cardiac chambers dimensions and LV filling pressures without changing systolic performance during an 8-week follow-up in hypertensive hemodialysis patients. more...

Background Data from the European Atrial Fibrillation (AF) Ablation Long-Term Registry suggest that there are significant differences in the volume of AF ablation procedures performed across different centers even in the same country. If these differences in AF ablation volume between centers reflect regional, socioeconomic, infrastructural/technical or other disparities has not been addressed till now. Purpose The aim of this study was to investigate patient and non-patient related differences among European AF ablation centers according to the volume of AF ablations performed. Methods Data for this analysis originate from the European AF Ablation Long-Term Study, a prospective registry designed to describe the clinical epidemiology of patients undergoing AF ablation. Based on 25th and 75th percentiles of AF ablation numbers performed, the participating centers were classified into high volume (HV) (≥250 procedures/year), medium volume (MV) ( Results A total of 91 centers in 26 European countries enrolled 3368 patients. There were no significant differences concerning regional distribution, hospital/cardiology facilities or services provided among centers with the exception of electrophysiology procedures and labs which were more abundant in HV centers (p=0.02 and Conclusions Volume of AF ablations in a center is not correlated with regional or infrastructural characteristics. The higher volume in HV centers consists mainly by more long-term persistent AF and higher risk patients, suggesting that differences in volume reflect differences in experience and personnel's commitment towards AF ablation. more...

Objectives To define the optimal timing for percutaneous pulmonary valve implantation (PPVI) in patients with severe pulmonary regurgitation (PR) after Fallot's Tetralogy (ToF) correction. Background PPVI among the aforementioned patients is mainly driven by symptoms or by severe right ventricular (RV) dilatation/dysfunction. The optimal timing for PPVI is still disputed. Methods Twenty patients [age 13.9 ± 9.2 years, (range 4.3–44.9), male 70%] with severe PR (≥3 grade) secondary to previous correction of ToF, underwent Melody valve (Medtronic, Minneapolis, MN) implantation, after a pre-stent placement. Full echocardiographic assessment (traditional and deformation analysis) and cardiovascular magnetic resonance evaluation were performed before and at 3 months after the intervention. ‘Favorable remodelling’ was considered the upper quartile of RV size decrease (>20% in 3 months). Results After PPVI, indexed RV effective stroke volume increased from 38.4 ± 9.5 to 51.4 ± 10.7 mL/m2, (P = 0.005), while RV end-diastolic volume and strain indices decreased (123.1 ± 24.1–101.5 ± 18.3 mL/m2, P = 0.005 and −23.5 ± 2.5 to −21 ± 2.5%, P = 0.002, respectively). After inserting pre-PPVI clinical, RV volumetric and deformation parameters in a multiple regression model, only time after last surgical correction causing PR remained as significant regressor of RV remodelling [R2 = 0.60, beta = 0.387, 95%CI(0.07–0.7), P = 0.019]. Volume reduction and functional improvement were more pronounced in patients treated with PPVI earlier than 7 years after last RV outflow tract (RVOT) correction, reaching close-to-normal values. Conclusions Early PPVI ( more...

Aims Left ventricular (LV) dilatation results in increased sphericity and affects position and orientation of papillary muscles (PMs), which may influence their performed work. The aim of this study was to assess the contribution of PM to LV function and its changes with dilatation. Methods and results Fifteen sheep were investigated. Ten animals were subjected to 8 weeks of rapid (180 bpm) pacing, inducing LV dilatation. Five animals served as controls. High-resolution gated computed tomography was performed to assess LV volumes, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), sphericity index, and PM angle, width and fractional shortening. 18F-fluorodeoxyglucose positron emission tomography (PET) was used to measure glucose metabolism as surrogate of regional myocardial work. Spatial resolution of PET images was maximized by electrocardiogram- and respiratory-gating. 18F-fluorodeoxyglucose uptake was measured in PM and compared with remaining left ventricular myocardium (MYO) to obtain a PM/MYO ratio. Animals with dilated heart had a more spherical left ventricle, with reduced LVEF (P more...

Objective Ultrafiltration rate is one of the major determinants of adverse outcomes in patients undergoing hemodialysis (HD) therapy. Previous studies have focused on the impact of HD on right ventricular (RV) peak strain values. However, the influence of HD on the temporal characteristics of deformation has not been reported yet. The aim of the present study was to evaluate the impact of high ultrafiltration rate (HUR) on RV mechanical dyssynchrony. Methods Echocardiographic images focused on the RV and left ventricle (LV) were obtained from 60 patients (49.2+-17.3 years, 22 female) before and after HD. Patients were divided into two groups according to ultrafiltration rate. Changes in echocardiographic parameters with HD were examined. Two-dimensional speckle-tracking strain analysis was used to assess deformation. Mechanical dispersion was measured as the standard deviation of time to peak longitudinal strain of six segments for RV and 18 segments for LV. Results The average ultrafiltrated volume and ultrafiltration rate were 3000.1+-1007.9 mL and 11.4+-2.9 mL/kg/h, respectively. Global longitudinal strain (GLS) of the RV and LV decreased after HD in both groups. A significant difference was observed in RV mechanical dispersion with HD for patients in the high ultrafiltration group. A mild statistically insignificant increase in LV mechanical dispersion was also observed after HD. Conclusion HUR has a substantial impact on LV and RV GLS and RV dyssynchrony. Ultrafiltration rates and volumes should be kept as low as possible to achieve hemodynamic stability and tolerability. more...

INTRODUCTION: Preventing sudden cardiac death (SCD) is one of the main goals in hypertrophic cardiomyopathy (HCM). Many variables have been proposed, however the European and American guidelines do not incorporate any ECG or Holter monitoring derived variables other than the presence of ventricular arrhythmia in their risk stratification models. In the present study we evaluated electrocardiographic parameters in risk stratification of HCM. METHODS AND RESULTS: Novel electrocardiographic parameters including the index of cardio-electrophysiological balance (iCEB), individualized QT correction (QTi) and QT rate dependence were evaluated along with established risk factors. A composite endpoint of SCD was defined as out of hospital cardiac arrest, appropriate ICD shock and sustained ventricular tachycardia. Cox regression analysis was used to evaluate predictors of SCD. Out of the 466 HCM patients, 31 reached the composite endpoint during a follow up of 75 ± 86 months. In a multivariate model, nor iCEB, QTi or QT rate dependence were predictors of SCD. Only male gender (p more...

Cirrhosis is commonly associated with impaired left ventricular (LV) myocardial contractile reserve to stress and diastolic dysfunction. The aim of this study was to assess LV systolic performance at rest, using both "standard" echocardiographic indices and novel deformation-rotational parameters, in order to elucidate the pathophysiologic basis of cardiac dysfunction in cirrhosis. Seventy-seven men with cirrhosis (mean age 54.4 ± 9.7) of variable Child-Pugh class (A, B, C) and 20 healthy control subjects were prospectively evaluated by standard as well as speckle tracking echocardiography. Left ventricular ejection fraction (LVEF) was significantly higher in patients with cirrhosis compared to controls (64.6 ± 5.7% in controls vs. 71 ± 9.5%, 71.2 ± 7.1%, and 73 ± 7% in Child-Pugh classes A, B, and C, respectively, P = 0.002). Interestingly, LV systolic function augmentation was not associated with changes in LV longitudinal deformation (LV strain -19 ± 1.9% in controls vs. -20.1 ± 5.3% in class A vs. -21.3 ± 2.6% in class B vs. -21 ± 3.4% in class C, P = NS), but a statistically significant increase in LV apical systolic rotation and accordingly in LV twist was observed (LV twist 13.0 ± 3° in controls vs. 14.9 ± 5° in class A vs. 16.5 ± 2.8° in class B vs. 18.2 ± 2.9° in class C, P < 0.0005). Despite the increase in LV rotation, time to both basal and apical peak systolic rotation was significantly delayed in patients compared to healthy controls (P = 0.015 and P = 0.017 accordingly). Increased EF in cirrhosis could be attributed to increased LV torsion. Despite the "improved" rotation values at rest, there is a significant time delay in succeeding peak systolic rotation, hampering also the consequent untwisting-diastolic period. more...

Heart failure with preserved ejection fraction (HFpEF). Arterial hypertension (AH), arterial stiffness (AS), older age, and female gender are the main determinants of HFpEF, but several cardiac or extra-cardiac pathologies are also possible causes. The combined ventricular-vascular stiffening (abnormal left atrium-left ventricle coupling related to AS) is the main contributor of the increased prevalence of HFpEF in elderly persons, particularly elderly women, and in younger persons with AH. The hospitalization and mortality rates of HFpEF are similar to those of heart failure with reduced EF (HFrEF). However, although the prognosis of HFrEF has been substantially improved during the last 2 decades, the effective treatment of HFpEF remains an unmet need. Regimens effective in HFrEF have no substantial effect on HFpEF, because of different pathophysiologies of the 2 syndromes. Pipeline drugs seem promising, but it will take some years before they are commercially available. Aggressive treatment of noncardiac comorbidities seems to be the only option at hand. Treatment of anaemia, sleep disorders, chronic kidney disease (CKD), non-alcoholic fatty liver (NAFLD), atrial fibrillation, diabetes, and careful use of diuretics to reduce preload are effective to some degree. Statin treatment, despite the presence of dyslipidaemia, deserves special attention because it has been proven, mainly in small studies or post hoc analyses of trials, that it offers a substantial improvement in quality of life and a reduction in mortality rates. We need to urgently utilize these recourses to relieve a considerable part of the general population suffering from HFpEF, a deadly disease. more...

It is widely known that various factors contribute to left atrial (LA) mechanical dysfunction in patients with end stage renal disease (ESRD). However, the connection between atrial dysfunction and arrhythmic events such as paroxysmal atrial fibrillation (PAF), in this group of patients, remains unclear. The purpose of our study was to evaluate prospectively the association between LA deformation indices and PAF in ESRD patients. 79 patients (41 men, mean age 57 ± 17) with ESRD and preserved left ventricular systolic function comprised the study population. All patients underwent a baseline comprehensive echocardiography study and were followed for a mean period of 16 ± 5 months. PAF episodes, first and the following events, were reported. LA longitudinal strain reflecting LA reservoir function and LA longitudinal strain rate reflecting LA pump function were specifically evaluated as LA deformation indices of interest, using 2D speckle tracking echocardiography. At the end of follow up period nine patients died. 15 of the rest 70 reported one or more episodes of PAF. LA indexed volumes were significantly higher in patients with PAF (32 ± 26 vs. 21.5 ± 9 ml/m2, p = 0.002), mean LA strain was significantly reduced (17 ± 7 vs. 27 ± 9%, p more...

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Its clinical course is variable, ranging from a benign asymptomatic or mildly symptomatic course throughout life, to severe symptoms (dyspnea, angina, palpitations) or cardiovascular events (syncope and thromboembolism). Sudden cardiac death (SCD) remains the most striking manifestation of the disease, affecting a minority of patients. This review focuses on the medical treatments applied according to the symptomatology in obstructive and nonobstructive HCM; a special reference is made to atrial fibrillation and arterial hypertension, which often coexist with the disease. Current literature about the pharmaceutical prevention of SCD is also analyzed and novel pharmacologic agents and approaches that may represent the future management of HCM are critically reviewed. The analysis of interventional techniques that are used in cases of medical treatment failure is avoided. Rather than enumerating clinical studies and guidelines, this review provides a concise and contemporary analysis of HCM pharmacotherapy, developing applicable algorithms for clinicians and highlighting promising future drug regimens. more...

Background— A plethora of echo parameters has been suggested for distinguishing cardiac amyloidosis (CA) from other causes of myocardial thickening with, however, scarce data on their head-to-head comparison. This study aimed at comparing the diagnostic accuracy of various deformation and conventional echo parameters in differentiating CA from other hypertrophic substrates, especially in the gray zone of mild hypertrophy (maximum wall thickness ≤16 mm) or normal ejection fraction (EF). Methods and Results— We included 100 subjects, of which 40 were patients with newly diagnosed, biopsy-proven CA (65.5±10.8 years, 65% male, 62.5% amyloidosis light chain [AL] type), 40 patients with hypertrophic cardiomyopathy matched for demographics and maximum wall thickness (60.1±14.8 years, 85% male), and 20 hypertensives with prominent myocardial remodeling. Quantifiable conventional morphological and functional parameters along with multidimensional strain and strain-derived ratios indices, previously suggested to diagnose CA, were analyzed. EF global longitudinal strain ratio showed the best performance to discriminate CA (area under the curve, 0.95; 95% confidence intervals, 0.89–0.98; P P 55%), EF global longitudinal strain ratio remained the best predicting parameter of CA diagnosis (multiple logistic regression models P P =0.0002, respectively) independent of the CA type. Conclusions— Our study demonstrated that in patients with thickened hearts, EF global longitudinal strain ratio has the best accuracy in detecting CA, even among the most “challenging” patient subgroups as those with mild hypertrophy and normal EF. more...

A 50-year-old man was referred for further evaluation of progressive exertional dyspnoea, after initial echocardiography had shown a late-peaking ‘dagger-shaped’ flow profile (peak gradient at rest 65 mmHg) in the left ventricular outflow tract (LVOT), compatible with hypertrophic cardiomyopathy (HCM) ( Panel A ). Cardiovascular magnetic resonance revealed a basal septal thickness of 16 … more...

The identification of left ventricular hypertrophy (LVH) through electrocardiographic voltage criteria has been widely studied in patients. However, their validity in “athlete’s heart” remains quite unknown. The aim of this study was to evaluate the most common electrocardiographic indices indicative of LVH compared to the known echocardiographic ones in athletes. The study group comprised 150 male adult competitive athletes (group A) and 50 sedentary participants (group B). Thirteen accepted electrocardiographic voltage criteria indicative of LVH were calculated and correlated with the common echocardiographic indices of left ventricular mass (LVM). Nine of the 13 ECG voltage criteria were significantly increased in athletes compared to controls. Statistically, the Sokolow–Lyon index, which is the most commonly used voltage index was found to be affected by the body mass index (10.7 %, p < 0.05), the group (7.3 %, p < 0.05) and systolic blood pressure (4.5 %, p < 0.05) in total variance of 16.6 % (p < 0.05). No electrocardiographic voltage criterion was significantly correlated with any echocardiographic index, except for the Cornell index that was correlated with end-diastolic volume index (r = 0.29, p < 0.05) and the Sokolow index (V6) with LVMI (r = 0.26, p < 0.05) in group A. We suggested that ECG voltage indices should not be considered valid when assessing LVH in athletes. Thus, the echocardiographic study is preferable in studying training-induced structural cardiac changes. more...

Left ventricular hypertrophy (LVH) with intraventricular septum thickness (IVST) between 1.2 and 1.5 cm in athletes represents a "gray zone" between physiologic adaptation and mild hypertrophic cardiomyopathy (HCM). Various echo and laboratory parameters have been reported till now in the literature to discriminate the "gray zone" entities. Aim of this study was to assess the efficacy of these "classic" parameters in differentiating physiologic LVH in athletes from mild HCM in a highly selected population. Nine highly trained athletes with IVST (1.28 ± 0.07 cm), 9 patients with mild HCM (1.38 ± 0.11 cm), and 26 athletes without LVH (1.06 ± 0.09 cm; P 0.0005) underwent echocardiographic study, cardiopulmonary treadmill exercise stress test, and brain natriuretic peptide (BNP) measurement before and after exercise. Among all parameters tested, 7 were found to significantly differ between "gray zone" groups. After bootstrapping analysis, it was found that athletes with left ventricular end-diastolic diameter4.74 cm, mitral deceleration time200 ms, isovolumic relaxation time94 ms, tricuspid E/A 1.63, septum Em 9.5 cm/sec, relative wall thickness0.445, and a BNP value at rest9.84 pg/mL had a greater possibility for having underlying cardiomyopathy. A 10-point score based on these parameters showed accuracy (area under the curve = 0.958 [95%CI: 0.738-1.0; P = 0.00005, standard error = 0.0342]) for revealing HCM in a gray zone athletic population. Differentiation of adaptive LVH versus HCM in a gray zone population could be facilitated by recognition of certain features referring to LV dimensions, diastolic function, and BNP. more...

Ranolazine, an antianginal agent with antiarrhythmic properties, prevents atrial fibrillation (AF) in patients with acute coronary syndrome. In experimental models, the combination of ranolazine and amiodarone has marked synergistic effects that potently suppress AF. Currently, the clinical effect of the ranolazine-amiodarone combination for the conversion of AF is unknown. This prospective randomized pilot study compared the safety and efficacy of ranolazine plus amiodarone versus amiodarone alone for the conversion of recent-onset AF. We enrolled 51 consecutive patients with AF (48-hour duration) eligible for pharmacologic cardioversion. Patients (33 men, 63 ± 8 years of age) were randomized to intravenous amiodarone for 24 hours (group A, n = 26) or to intravenous amiodarone plus oral ranolazine 1,500 mg at time of randomization (group A + R, n = 25). The 2 groups were well balanced with respect to clinical characteristics and left atrial diameter. Conversion within 24 hours (primary end point) was achieved in 22 patients (88%) in group A + R versus 17 patients (65%) in group A (p = 0.056). Time to conversion was shorter in group A + R than in group A (9.8 ± 4.1 vs 14.6 ± 5.3 hours, p = 0.002). According to Cox regression analysis, left atrial diameter and A + R treatment were the only independent predictors of time to conversion (hazard ratio 5.35, 95% confidence interval 2.37 to 12.11, p0.001; hazard ratio 0.81, 95% confidence interval 0.74 to 0.88, p0.001, respectively). There were no proarrhythmic events in either group. In conclusion, addition of ranolazine to standard amiodarone therapy is equally safe and appears to be more effective compared to amiodarone alone for conversion of recent-onset AF. more...

Background Diminished functional capacity is common in hypertrophic cardiomyopathy (HCM), although the underlying mechanisms are complicated. We studied the prevalence of chronotropic incompetence and its relation to exercise intolerance in patients with HCM. Methods Cardiopulmonary exercise testing was performed in 68 patients with HCM (age 44.8±14.6years, 45 males). Chronotropic incompetence was defined by chronotropic index (heart rate reserve)/(220-age-resting heart rate) and exercise capacity was assessed by peak oxygen consumption (peak Vo 2 ). Results Chronotropic incompetence was present in 50% of the patients and was associated with higher NYHA class, history of atrial fibrillation, higher fibrosis burden on cardiac MRI, and treatment with β-blockers, amiodarone and warfarin. On univariate analysis, male gender, age, NYHA class, maximal wall thickness, left atrial diameter, peak early diastolic myocardial velocity of the lateral mitral annulus, history of atrial fibrillation, presence of left ventricular outflow tract obstruction (LVOTO) at rest, and treatment with beta-blockers were related to peak Vo 2 . Peak heart rate during exercise, heart rate reserve, chronotropic index, and peak systolic blood pressure were also related to peak Vo 2 . On multivariate analysis male gender, atrial fibrillation, presence of LVOTO and heart rate reserve were independent predictors of exercise capacity (R 2 =76.7%). A cutoff of 62bpm for the heart rate reserve showed a negative predictive value of 100% in predicting patients with a peak Vo 2 Conclusions Blunted heart rate response to exercise is common in HCM and represents an important determinant of exercise capacity. more...

Summary Background Long-term statin treatment reduces the frequency of cardiovascular events, but safety and efficacy in patients with abnormal liver tests is unclear. We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study population. Methods GREACE was a prospective, intention-to-treat study that randomly assigned by a computer-generated randomisation list 1600 patients with coronary heart disease (aged 2·6 mmol/L and triglycerides Findings Of 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p vs 117 [23%] in 510 patients not receiving a statin [7·6 per 100 patient-years]; 39% relative risk reduction, p Interpretation Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease. Funding None. more...

Background: The role of brain natriuretic peptide (BNP) in differentiating the athlete’s heart from maladaptive cardiac hypertrophy is unclear. Methods: To address this issue, an integrated M mode, two-dimensional B mode and Doppler echocardiographical study were performed and plasma BNP levels were measured in 25 strength athletes, 25 patients with established hypertrophic cardiomyopathy (HCM) and 25 healthy volunteers. Results: Among athletes, BNP levels correlated negatively with the total training time (r = −0.79, p = 0.002) and positively with ejection fraction (r = 0.58, p = 0.049) and fractional shortening (r = 0.57, p = 0.049). A BNP cut-off value of 11.8 pg/ml had 88% specificity and 74% negative predictive value for the exclusion of HCM. Conclusions: Brain natriuretic peptide might be useful as a preparticipation screening test in athletes. more...

The effect of left ventricular outflow tract obstruction (LVOTO) at rest on the incidence of sudden death (SD) in patients with hypertrophic cardiomyopathy is rather conflicting. The aim of this study was the evaluation of LVOTO at rest as a new potential risk factor for SD in hypertrophic cardiomyopathy. A total of 166 patients (112 men, 51.8 +/- 15.6 years) were studied; 50 patients (30.1%) had peak instantaneous LVOTO gradients of > or = 30 mm Hg at rest. During the follow-up period (median 32.4 months, range 1 to 209), 13 patients either died suddenly, or had cardiac arrest, documented sustained ventricular tachycardia, or implantable cardioverter defibrillator discharge. The cumulative event-free survival rate was 92% in patients with LVOTO, and 92% in patients without obstruction (p = NS). LVOTO at rest was associated with a particularly low positive predictive value for SD (8%), although a high negative predictive value (92%) was recorded. Patients having syncope or presenting with a maximum wall thickness > or =3 cm in echocardiography were more sensitive to SD emergence because they had a 13.07 (95% confidence interval 4.00 to 46.95, p more...

The cardiorenal anemia syndrome in congestive heart failure (CHF) is an independent risk factor for vascular morbidity and mortality. Several factors play a role in the pathogenesis of anemia in CHF, including inflammation, impaired renal function, use of certain antihypertensive or cardioprotective agents, and gastrointestinal or urinary losses of essential hemopoietic factors. Several trials evaluated the effects of administering erythropoietin (EPO) and/or iron to patients with CHF. Even though most of them were uncontrolled studies, their results suggest that EPO treatment might be beneficial in CHF. Nevertheless, more studies are needed and certain issues should be resolved, particularly the optimal hemoglobin level, before EPO can become part of the treatment of patients with CHF. more...

Reducing low-density lipoprotein cholesterol (LDL-C) levels to National Cholesterol Expert Panel (NCEP) goal is recommended. However, sex-specific effects may influence benefit.In this post hoc analysis of the GREek Atorvastatin and Coronary heart disease (CHD) Evaluation [GREACE] study we investigated the extent in vascular event reduction by statin treatment according to sex. From a total of 1600 patients with stable CHD, 624/176 and 632/168 were men/women on atorvastatin or on usual care, respectively. During 3-year follow-up, comparison of atorvastatin treatment with usual care demonstrated a relative risk reduction (RRR) of the primary end point (all vascular events) of 54% in women (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.24-0.87, p=0.003) and of 50% in men (HR 0.50, 95% CI 0.32-0.70, p0.001). The fall in LDL-C levels played the key role in end point reduction in both sexes. However, in men there was an additional benefit related to the atorvastatin-induced increase in high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR), while in women end points were related to a substantial triglycerides (TG) reduction.Treatment with atorvastatin to the NCEP LDL-C goal compared with 'usual care' significantly reduced CHD morbidity and mortality in both men and women. Both men and women benefited from statin treatment possibly with different mechanisms making a contribution over and above LDL-C reduction. more...

Aims Sudden cardiac death (SCD) may complicate hypertrophic cardiomyopathy (HCM) natural course. Patient selection for implantable cardioverter defibrillator (ICD) therapy in the primary prevention setting is still a challenge. Methods Thirty-seven HCM patients with a primary prevention ICD were included. All patients underwent preimplantation SCD risk assessment and semi-annual device interrogation during follow-up. Primary end point was the time to first appropriate ICD intervention including antitachycardia pacing or shock. Inappropriately delivered ICD therapies served as secondary end point. Results During a median follow-up of 3.1 years, 10 (27%) patients received one or more appropriate ICD therapies. First appropriate ICD intervention rate was 7.2%/year (95% CI: 3.4-13.2) with a 5-year cumulative probability of 29.2 ± 7.4%. No SCD risk marker was significantly associated with the primary end point, whereas event rates were comparable among patients with one, two or three or more SCD risk markers (log-rank P = 0.58). Patients with a history of SCD in first-degree relatives with HCM were at 3.8 times higher risk of experiencing an ICD intervention compared with those with no family history of SCD (HR: 3.8; 95% CI: 1.0-14.1, P = 0.05). Seven (18.9%) patients experienced one or more inappropriate ICD therapies; beta-blocker therapy was associated with 75% fewer inappropriate ICD interventions (HR: 0.15; 95% CI: 0.03-0.89). Conclusion Current criteria identify a subgroup of patients with HCM at increased risk of major arrhythmic events as indicated by high ICD intervention rates. However, no individual risk marker demonstrated superior predictive ability over the others, whereas simple arithmetic summing of risk markers was not associated with increased ICD intervention rates. more...

High triacylglycerol (TAG) levels may predict vascular risk. The effect of a statin-induced reduction in TAG levels, irrespective of HDL-C increase, on clinical outcome has not yet been addressed by an endpoint study in patients with coronary heart disease (CHD). The GREACE study compared usual with structured care aimed at achieving LDL-C = 100 mg/dL (2.6 mmol/L) by dose titration with atorvastatin. All patients had CHD and were followed for 3 years. This post hoc analysis of GREACE examines the effect of statins on TAG levels and their relation with cardiovascular disease (CVD) events in all patients and in the subgroup of patients with metabolic syndrome (MetS). Baseline TAG levels >150 mg/dL (1.7 mmol/L) were predictive of subsequent CVD events [cardiac mortality, non-fatal myocardial infarction (MI), unstable angina (UA), revascularisation, congestive heart failure (CHF), and stroke] only in statin untreated patients. Stepwise regression analysis showed that with every 20% statin-related TAG reduction there was a decrease in CVD risk by 12% (HR 0.88, 95% CI 0.75–0.95, P = 0.007) in the structured care group vs. the usual care group, by 8% (HR 0.92, 95% CI 0.81–0.97, P = 0.02) in all statin treated patients vs. the untreated ones and by 15% (HR 0.85, 95% CI 0.65–0.94, P = 0.005) in those with MetS treated with a statin vs. those untreated. Using the same analysis but only taking into consideration vascular events (cardiac mortality, non-fatal MI, UA, revascularisation, and stroke) there was a 18% (HR = 0.82, 95% CI 0.57–0.96, P = 0.03) decrease in risk in the MetS (+) patients treated with a statin vs. those not on a statin, and a decrease in risk by 16% (HR = 0.84, 95% CI 0.53–1.07, P = 0.08), when only hard vascular endpoints (cardiac mortality, non-fatal MI, and stroke) were considered. TAG levels are predictive of subsequent CVD events in statin untreated CHD patients. Statin (mainly atorvastatin)-induced decrease in TAG levels was related to a significant reduction in subsequent CVD events. This benefit was more pronounced in CHD MetS (+) patients. more...

Preclinical diagnosis in hypertrophic cardiomyopathy (HCM) refers to the detection of functional or histopathological abnormalities in subjects who carry any HCM-causing gene mutation, before or even without the development of left ventricular hypertrophy [genotype(+)/phenotype(-)subjects]. The concept that HCM pathology may exist in the absence of left ventricular hypertrophy is quite old but the ability to recognize the presence of early myocardial changes is quite new. Lessons from animal models have shown that in experimental human HCM, myocardial cell mechanical dysfunction precedes histopathological changes, such as myocyte disarray, fibrosis, and hypertrophy. Several clinical reports have demonstrated that the majority of HCM genotype(+)/phenotype(-) subjects display myocardial functional or histopathological changes, such as reduced tissue Doppler imaging-derived systolic and diastolic velocities, abnormal electrocardiogram, cardiac magnetic resonance-visualized myocardial crypts, mitral leaflet elongation, and evidence of a fibrotic state, such as increased type I procollagen synthesis, cardiac magnetic resonance-increased myocardial extracellular volume, and late gadolinium myocardial enhancement. All these signs have been proposed as preclinical markers of HCM. At present the separation of such a group of subjects in the early phase of their disease provides the opportunity to test new therapies to prevent the development of fibrosis, hypertrophy, and dysfunction. more...