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OBJECTIVES: Data on the impact and course of uncorrected tricuspid regurgitation (TR) during left ventricular assist device (LVAD) implantation are scarce and inconsistent. This study explores the clinical impact and natural course of uncorrected TR in patients after LVAD implantation. METHODS: The European Registry for Patients with Mechanical Circulatory Support was used to identify adult patients with LVAD implants without concomitant tricuspid valve surgery. A mediation model was developed to assess the association of TR with 30-day mortality via other risk factors. Generalized mixed models were used to model the course of post-LVAD TR. Joint models were used to perform sensitivity analyses. RESULTS: A total of 2496 procedures were included (median age: 56 years; men: 83%). TR was not directly associated with higher 30-day mortality, but mediation analyses suggested an indirect association via preoperative elevated right atrial pressure and creatinine (P = 0.035) and bilirubin (P = 0.027) levels. Post-LVAD TR was also associated with increased late mortality [hazard ratio 1.16 (1.06-1.3); P = 0.001]. On average, uncorrected TR diminished after LVAD implantation. The probability of having moderate-to-severe TR immediately after an implant in patients with none-to-mild TR pre-LVAD was 10%; in patients with moderate-to-severe TR pre-LVAD, it was 35% and continued to decrease in patients with moderate-to-severe TR pre-LVAD, regardless of pre-LVAD right ventricular failure or pulmonary hypertension. CONCLUSIONS: Uncorrected TR pre-LVAD and post-LVAD is associated with increased early and late mortality. Nevertheless, on average, TR diminishes progre

Objectives: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides a temporary support system for patients with cardiogenic shock refractory to conventional medical therapies. It has been reported that levosimendan may facilitate VA-ECMO weaning and improve survival. The primary objective of this review was to examine the effect of levosimendan use on VA-ECMO weaning and mortality in critically ill patients on VA-ECMO. Design: MEDLINE, EMBASE, and CENTRAL were searched. A pair of reviewers identified eligible clinical trials. Two reviewers extracted data and independently assessed the risk of bias. A random-effect model was used to combine data. The primary outcome was the success of weaning from VA-ECMO. Measurements and Main Results: Seven studies of observational design, including a total of 630 patients, were selected in the final analysis. The sample size ranged from ten-to-240 patients, with a mean age between 53 and 65 years, and more than half of them underwent cardiac surgeries. The VA-ECMO durations varied between four and 11.6 days. Overall, levosimendan use was significantly associated with successful weaning compared with control (odds ratio [OR] 2.89, 95% CI, 1.53-5.46; poverall effect = 0.001); I2 = 49%). For survival, six studies (n = 617) were included in the meta-analysis involving 326 patients in the levosimendan group and 291 in the comparator group. Pooled results showed a significantly higher survival rate in the levosimendan group (OR 0.46, 95% CI, 0.30-0.71; poverall effect = 0.0004; I2 = 20%). Conclusions: Levosimendan therapy was significantly associated with successful weaning and survival benefit in patients with cardiogenic or postcardiotomy shock needing VA-ECMO support for severe cardiocirculatory compromise. To date, there is limited literature and absence of evidence from randomized trials addressing the use of levosimendan in VA-ECMO weaning. This study may be considered a hypothesis-generating research for randomized

AIMS: To evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing percutaneous coronary interventions (PCIs) in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as adverse event (AE) that may lead to treatment non-adherence. METHODS AND RESULTS: This is a non-prespecified, post hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-mon

Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy.

Background: Many patients undergoing durable left ventricular assist device (LVAD) implantation suffer from chronic kidney disease (CKD). Therefore, we investigated the effect of LVAD support on CKD. Methods: A retrospective multicenter cohort study, including all patients undergoing LVAD (HeartMate II (n = 330), HeartMate 3 (n = 22) and HeartWare (n = 48) implantation. In total, 227 (56.8%) patients were implanted as bridge-to-transplantation; 154 (38.5%) as destination therapy; and 19 (4.7%) as bridge-to-decision. Serum creatinine measurements were collected over a 2-year follow-up period. Patients were stratified based on CKD stage. Results: Overall, 400 patients (mean age 53 ± 14 years, 75% male) were included: 186 (46.5%) patients had CKD stage 1 or 2; 93 (23.3%) had CKD stage 3a; 82 (20.5%) had CKD stage 3b; and 39 (9.8%) had CKD stage 4 or 5 prior to LVAD implantation. During a median follow-up of 179 days (IQR 28–627), 32,629 creatinine measurements were available. Improvement of kidney function was noticed in every preoperative CKD-stage group. Following this improvement, estimated glomerular filtration rates regressed to baseline values for all CKD stages. Patients showing early renal function improvement were younger and in worse preoperative condition. Moreover, survival rates were higher in patients showing early improvement (69% vs 56%, log-rank P = 0.013). Conclusions: Renal function following LVAD implantation is characterized by improvement, steady state and subsequent deterioration. Patients who showed early renal function improvement were in worse preoperative condition, however, and had higher survival rates at 2 years of follow-up.

BACKGROUND: While rheumatic mitral stenosis has been effectively treated percutaneously for more than 20 years, mitral and tricuspid regurgitation treatment appear as a contemporary unmet need. The advent of transcatheter therapies offer new treatment options to often elderly and frail patients at high risk for open surgery. We aimed at providing an updated review of fast-growing domain of transcatheter mitral and tricuspid technology. MAIN BODY: We reviewed the existing literature on mitral and tricuspid transcatheter therapies. Mitraclip is becoming an established therapy for secondary mitral regurgitation in selected patients with disproportionately severe regurgitation associated with moderate left ventricle dysfunction. Evidence is less convincing for primary mitral regurgitation. Transcatheter mitral valve replacement is a promising emerging alternative to transcatheter repair, for secondary as well as primary mitral regurgitation. But further development is needed to improve delivery. Transcatheter tricuspid intervention arrives late after similar technologies have been developed for aortic and mitral valves and is currently at its infancy. This is likely due in part to previously under-recognized impact of tricuspid regurgitation on patient outcomes. Edge-to-edge repair is the most advanced transcatheter solution in development. Data on tricuspid annuloplasty and replacement is limited, and more research is warranted. CONCLUSION: The future appears bright for transcatheter mitral therapies, albeit their place in clinical practice is yet to be clearly defined. Tricuspid transcatheter therapies might address the unmet need of tricuspid regurgitation treatment.

Purpose: The aim of the study was to analyze early mortality after continuous-flow left ventricular assist device (LVAD) implantation which remains high. Methods: We analyzed consecutive (n = 2689) patients from the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) undergoing continuous-flow LVAD implantation. The primary outcome was early (< 90 days) mortality. Secondary outcomes were differential causes of early post-operative death following LVAD implantation. Results: Univariable and multivariable analysis as well as regression analysis were used to examine determinants and differential causes of early (< 90 days) mortality after LVAD implantation. During the first 90 days, 2160 (80%) patients were alive with ongoing LVAD support, 40(2%) patients underwent heart transplantation, and 487(18%) deceased. The main causes of early death were MOF (36%), sepsis (28%), cardiopulmonary failure (CPF; 10%), CVA (9%), and right-sided heart failure (RHF, 8%). Furthermore, MOF and sepsis are 70% of causes of death in the first week. Independent clinical predictors of early death were age, female sex, INTERMACS profile 1 to 3, and ECMO. Laboratory predictors included elevated serum creatinine, total bilirubin, lactate, and low hemoglobin. Furthermore, hemodynamic predictors included elevated RA-to-PCWP ratio, pulmonary vascular resistance, and low systemic vascular resistance. Longer total implantation time was also independent predictor of early mortality. A simple model of 12 variables predicts early mortality following LVAD implantation with a good discriminative power with area under the curve of 0.75. Conclusions: In the EUROMACS registry, approximately one out of five patients die within 90 days after LVAD implantation. Early mortality is primarily dominated by multiorgan failure followed by sepsis. A simple model identifies important parameters which are associated with early mortality following LVAD implantation.

Aims: Patients with bicuspid valves represent a challenging anatomical subgroup for transcatheter aortic valve implantation (TAVI). This analysis evaluated the clinical outcomes of the fully repositionable and retrievable Lotus Valve System in patients with bicuspid aortic valves enrolled in the RESPOND post-market registry. Methods and Results: The prospective, open-label RESPOND study enrolled 1,014 patients at 41 centers in Europe, New Zealand, and Latin America, 31 (3.1%) of whom had bicuspid aortic valves. The mean age in the bicuspid patient cohort was 76.4 years, 64.5% were male, and the baseline STS score was 6.0 ± 10.2. Procedural success was 100%, with no cases of malpositioning, valve migration, embolization, or valve-in-valve. Repositioning was attempted in 10 cases (32.3%). There was one death (3.2%) and one stroke (3.2%) at 30-day follow-up. Mean AV gradient was reduced from 48.7 ± 17.0 mmHg at baseline to 11.8 ± 5.1 mmHg at hospital discharge (P < 0.001); mean effective orifice area (EOA)

Background: We investigated the relationship between intraprocedural angiographic and echocardiographic AR severity after TAVI, and the clinical robustness of angiographic assessment. Methods and Results: In 74 consecutive patients, the echocardiographic circumferential extent (CE) of the paravalvular regurgitant jet was retrospectively measured and graded based on the VARC-2 cut-points; and angiographic post-TAVI AR was retrospectively quantified using contrast videodensitometry (VD) software that calculates the ratio of the contrast time-density integral in the LV outflow tract to that in the ascending aorta (LVOT-AR). Seventy-four echocardiograms immediately after TAVI were analyzable, while 51 aortograms were analyzable for VD. These 51 echocardiograms and VD were evaluated. Median LVOT-AR across the echocardiographic AR grades was as follows: none-trace, 0.07 (IQR, 0.05–0.11); mild, 0.12 (IQR, 0.09–0.15); and moderate, 0.17 (IQR, 0.15–0.22; P<0.05 for none-trace vs. mild, and mild vs. moderate). LVOT-AR strongly correlated with %CE (r=0.72, P<0.0001). At 1 year, the rate of the composite end-point of all-cause death or HF re-hospitalization was significantly higher in >mild AR patients compared with no-mild AR on intra-procedural echocardiography (41.5% vs. 12.4%, P=0.03) as well as in patients with LVOT-AR >0.17 compared with LVOT-AR ≤0.17 (59.5% vs. 16.6%, P=0.03). Conclusions: VD (LVOT-AR) has good intra-procedural inter-technique consistency and clinical robustness. Greater than mild post-TAVI AR, but not mild post-TAVI AR, is associated with late mortality.

Aims: Videodensitometric assessment of aortography provides a periprocedural quantitation of prosthetic valve regurgitation (PVR) after transcatheter aortic valve implantation. We sought to compare the videodensitometric parameters of PVR severity to the regurgitation fraction (RF) in a controlled in vitro setting. Methods and results: In a mock circulation system, a transcatheter balloon-expandable valve inserted at the aortic valve position was gradually deformed to induce different grades of paravalvular leakage and the RF was measured with a transonic flow probe. Contrast aortography was performed and the following videodensitometric parameters were generated: left ventricle aortic regurgitation (LV-AR), LV outflow tract AR (LVOT-AR), quantitative regurgitation assessment (qRA) index, relative maximum density (relative max), and maximum upslope of the LV time-density curve. The correlation was substantial between videodensitometric parameters (LV-AR, LVOT-AR, qRA index, relative max, and maximum upslope) and RF (r 2=0.96, 0.96, 0.93, 0.87, and 0.93; p<0.001 for all). LV-AR (region of interest [ROI]=entire LV) and LVOT-AR (ROI=LVOT) were not different (p=0.51) and were strongly correlated (r 2=0.99) with a mean difference of 1.92% (95% limits of agreement: ±2.83). The correlations of LV-AR and LVOT-AR with RF were stronger when more than one cardiac cycle was included in the analysis (one cycle: r 2=0.85 and r 2=0.83; four cycles: r 2=0.96 and r 2=0.96, for LV-AR and LVOT-AR, respectively). Including more cycles beyond four did not improve accuracy. Conclusions: Quantitative assessment of PVR by videodensitometry of aortograms strongly correlates with the actual RF in a controlled in vitro setting. Accuracy is improved by including more than one cardiac cycle in the analysis.

The increasing interest in left atrial appendage occlusion (LAAO) for ischaemic stroke prevention in atrial fibrillation (AF) fuels the need for more

Background The echocardiographic focus to detect abnormalities in genetically hypertrophic cardiomyopathy (HCM) affected subjects without left ventricular (LV) hypertrophy (G+/LVH-) has been on diastolic abnormalities in transmitral flow and longitudinal myocardial function with tissue Doppler imaging. The aim of this study was to assess diastolic LV unstrain and untwist. Methods and results Forty-one consecutive genotyped family members of HCM patients (mean age 37611 years, 16 men) and 41 ageand gender-matched healthy volunteers underwent speckle-tracking echocardiography to measure untwist and unstrain. No significant differences between G+/LVH- and control subjects were seen in maximal systolic twist and global longitudinal strain. In diastole, the early peak untwist rate was significantly lower in G+/LVH- subjects compared with control subjects (62±19°s-1 vs. 76±30°s-1, P<0.05), whereas the late peak untwist rate tended to be higher. Untwist from maximal twist until the first 20% of diastole was delayed in G+/LVH- subjects (39.3612.9% vs. 51.3±15.6%, P<0.005). Late diastolic unstrain rate was significantly higher in G+/LVH- subjects in the inferoseptal wall (111±33 s-1 vs. 94±32 s-1, P=0.024), the inferolateral wall (105±42 vs. 75±35 s-1, P=0.007) and the anteroseptal wall (97±26 vs. 80±23 s-1, P=0.010). Unstrain from maximal twist until the first 20% of diastole was delayed in G+/LVH- subjects in the inferoseptal (18.9614.0% vs. 30.1±17.7%, P=0.005), inferolateral (27.1±16.3% vs. 39.2±18.0%, P=0.015) and anteroseptal (19.1±14.7% vs. 35.8±18.5%, P=0.0003) segments. Conclusions In mutation carriers, for HCM LV, untwist and unstrain are delayed and untwist rate

Aims Paravalvular aortic leakage (PVL) after transcatheter aortic valve implantation (TAVI) is a complication with potentially severe consequences. The relation between native aortic root calcium burden, stent frame eccentricity and PVL was not studied before. Methods and results Two-hundred-and-twenty-three consecutive patients with severe aortic stenosis who underwent TAVI with a Medtronic CoreValve SystemVC and who had available pre-discharge transthoracic echocardiography were studied. Echocardiographic stent inflow frame eccentricity was defined as major-minor diameter in a short-axis view >2 mm. PVL was scored according to the updated Valve Academic Research Consortium (VARC-2) recommendations. In a subgroup of 162 (73%) patients, the calcium Agatston score was available. Stent frame eccentricity was seen in 77 (35%) of patients. The correlation between the Agatston score and stent frame eccentricity was significant (q = 0.241, P = 0.003). Paravalvular leakage was absent in 91 cases (41%), mild in 67 (30%), moderate in 51 (23%), and severe in 14 (6%) cases. The correlation between stent frame eccentricity and PVL severity was significant (q = 0.525, P < 0.0001). There was a relation between particular eccentric stent frame shapes and the site of PVL. Conclusion Calcification of the aortic annulus is associated with a subsequent eccentric shape of the CoreValve prosthesis. This eccentric shape results in more PVL, with the localization of PVL related to the shape of stent frame.

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly adopted for the treatment of cardiogenic shock (CS). However, a marker of successful weaning remains largely unknown. Our hypothesis was that successful weaning is associated with sustained microcirculatory function during ECMO flow reduction. Therefore, we sought to test the usefulness of microcirculatory imaging in the same sublingual spot, using incident dark field (IDF) imaging in assessing successful weaning from VA-ECMO and compare IDF imaging with echocardiographic parameters. Methods: Weaning was performed by decreasing the VA-ECMO flow to 50% (F50) from the baseline.

Aims: In the minimalist transcatheter aortic valve implantation (TAVI) era, the usage of transoesophageal echocardiography has become restricted. Conversely, aortography has gained clinical ground in quantifying prosthetic valve regurgitation (PVR) during the procedure. In a mock circulation system, we sought to compare the contrast volume required and the accuracy of aortographic videodensitometric PVR assessment using a synchronised diastolic and standard (non-synchronised) injection aortography. Methods and results: Synchronised diastolic injection triggered by the signal stemming from the mock circulation was compared with standard non-synchronised injection. A transcatheter heart valve was implanted and was deformed step by step by advancing a screw perpendicularly to the cage of the valve in order to create increasing PVR. Quantitative measurement of PVR was derived from time-density curves of both a reference area (aortic root) and a region of interest (left ventricle) developed by a videodensitometric software. The volume of contrast required for the synchronised diastolic injection was significantly less than in the non-synchronised injection (8.1 [7.9-8.5] ml vs. 19.4 [19.2-19.9] ml, p<0.001). The correlation between the two methods was substantial (Spearman's coefficient rho ranging from 0.991 to 0.968). Intraobserver intra-class correlation coefficient for both methods of injection was 0.999 (95% CI: 0.996-1.000) for the synchronised diastolic and 0.999 (95% CI: 0.996-1.000) for the non-synchronised injection group. The mean difference in the rating was 0.17% and limits of agreement were ±1.64% for both groups. Conclusions: A short synchronised diastolic injection enables contrast volume reduction during aortography without compromising the accuracy of the quantitative assessment of PVR using videodensitometry.

Left ventricular hypertrophy (LVH), defined by an increase in left ventricular mass (LVM), is a common cardiac finding generally caused by an increase in pressure or volume load. Assessing severity of LVH is of great clinical value in terms of prognosis and treatment choices, as LVH severity grades correlate with the risk for presenting cardiovascular events. The three main cardiac parameters for the assessment of LVH are wall thickness, LVM, and LV geometry. Echocardiography, with large availability and low cost, is the technique of choice for their assessment. Consequently, reference values for LVH severity in clinical guidelines are based on this technique. However, cardiac magnetic resonance (CMR) and computed tomography (CT) are increasingly used in clinical practice, providing excellent image quality. Nevertheless, there is no extensive data to support reference values based on these techniques, while comparative studies between the three techniques show different results in wall thickness and LVM measurements. In this paper, we provide an overview of the different methodologies used to assess LVH severity with echocardiography, CMR and CT. We argue that establishing reference values per imaging modality, and possibly indexed to body surface area and classified per gender, ethnicity and age-group, might be essential for the correct classification of LVH severity.

Background Despite advances in pump technology, thromboembolic events/acute pump thrombosis remain potentially life-threatening complications in patients with continuous-flow left ventricular assist devices (CF-LVAD). We sought to determine early signs of thromboembolic event/ pump thrombosis in patients with CF-LVAD, which could lead to earlier intervention. Methods We analysed all HeartMate II recipients (n = 40) in our centre between December 2006 and July 2013. Thromboembolic event/pump thrombosis was defined as a transient ischaemic attack (TIA), ischaemic cerebrovascular accident (CVA), or pump thrombosis. Results During median LVAD support of 336 days [IQR: 182–808], 8 (20%) patients developed a thromboembolic event/pump thrombosis (six TIA/CVA, two pump thromboses). At the time of the thromboembolic event/pump thrombosis, significantly higher pump power was seen compared with the no-thrombosis group (8.2 ± 3.0 vs. 6.4 ± 1.4 W, p = 0.02), as well as a trend towards a lower pulse index (4.1 ± 1.5 vs. 5.0 ± 1.0, p = 0.05) and a trend towards higher pump flow (5.7 ± 1.0 vs. 4.9 ± 1.9 L m, p = 0.06). The thrombosis group had a more than fourfold higher lactate dehydrogenase (LDH) median 1548 [IQR: 754– 2379] vs. 363 [IQR: 325–443] U/L, p = 0.0001). Bacterial (n = 4) or viral (n = 1) infection was present in 5 out of 8 patients. LDH > 735 U/L predicted thromboembolic events/ pump thrombosis with a positive predictive value of 88%. Conclusions In patients with a CF-LVAD (HeartMate II), thromboembolic events and/or pump thrombosis are associated with symptoms and signs of acute haemolysis as manifested by a high LDH, elevated pump power and decreased pulse index, especially in the context of an infection.

Significant paravalvular leakage (PVL) after transcatheter aortic valve implantation (TAVI) is related to patient mortality. Predicting the development of PVL has focused on computed tomography (CT) derived variables but literature targeting CoreValve devices is limited, controversial, and did not make use of standardized echocardiographic methods. The study included 164 consecutive patients with severe aortic stenosis that underwent TAVI with a Medtronic CoreValve system©, with available pre-TAVI CT and pre-discharge transthoracic echocardiography. The predictive value for significant PVL of the CT-derived Agatston score, aortic annulus size and eccentricity, and “cover index” was assessed, according to both echocardiographic Valve Academic Research Consortium (VARC) criteria and angiographic Sellers criteria. Univariate predictors for more than mild PVL were the maximal diameter of the aortic annulus size (for both angiographic and echocardiographic assessment of PVL), cover index (for echocardiographic assessment of PVL only), and Agatston score (for

To assess the feasibility and accuracy in measuring left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) with Siemens single-beat real-time 3D transthoracic echocardiography. The LV volumes and EF were measured in 3D datasets acquired by six imaging modes (time-1-harmonic (T1H), time-1-fundamental, time-2-harmonic, time-2-fundamental, space-1-harmonic (S1H), and space-1-fundamental) in 41 patients using the automated contouring algorithm and compared with manually corrected 3DE QLAB measurements. The main determinates of the temporal and spatial resolutions of 3D datasets acquired were the fundamental and harmonic modes. Consequently, the S1H mode had the lowest volume rate and highest spatial resolution. Compared with the 3DE QLAB analysis, the S1H mode resulted in the best LV volumes and EF estimates in all patients (0 ± 10 % for EF, -7 ± 44 ml for EDV, -7 ± 39 ml for ESV) and in the 10 patients with correct LV contour tracking according to a visual assessment from the multiplanar reconstruction views in all six modes (0 ± 9 % for EF, -3 ± 23 ml for EDV, -2 ± 14 ml for ESV). The T1H mode was the best alternative. Overall 28 patients (68 %) could be analysed automatically and satisfyingly with the S1H and T1H modes: 0 ± 8 % (EF), 0 ± 27 ml (EDV) and -1 ± 16 ml (ESV). The accuracy of the Siemens automated RT-3D algorithm in measuring LV volumes and EF is significantly influenced by the different imaging modes. The S1H mode may be the preferred 3D acquisition mode, supplemented by the T1H mode in enlarged LVs that do not fit in the S1H acquisition sector.

Background: Noncompaction cardiomyopathy (NCCM) is characterized by a prominent trabecular meshwork and deep intertrabecular recesses. Although systolic dysfunction is common, limited information is available on differences in wall motion of the normal compacted and noncompacted segments. The purpose of this study was to assess radial wall motion and longitudinal wall velocity in patients with NCCM, according to the extent and severity of noncompaction. Methods. The study comprised 29 patients in sinus rhythm (age 41 15 years, 15 men), who fulfilled stringent diagnostic criteria for NCCM and compared to 29 age and gender matched healthy controls. Segmental radial wall motion of all compacted and noncompacted segments was assessed with the standard visual wall motion score index and longitudinal systolic (Sm) wall velocity with tissue Doppler imaging of the mitral annulus. For each

AimsComorbidity, such as myocardial infarction, diabetes, and renal failure, plays a pivotal role in the prognosis of a patient with arrhythmias. However, data on the prognostic impact of comorbiditiy in heart failure patients with cardiac resynchronization therapy and defibrillation (CRT-D) are scarce. The purpose of this study was to determine the impact of comorbidity on survival in CRT-D patients.Methods and resultsThe study population consisted of 463 heart failure patients who received a CRT-D between 1999 and 2008 in Rotterdam and Basel. The Charlson comorbidity index (CCI) is often used as an adjusting variable in prognostic models. The Cox proportional hazards analysis was performed to determine the independent effect of comorbidity on survival. During a median follow-up of 30.5 months, 85 patients died. Mortality rates at 1 and 7 years were 6.3 and 32.3. Cumulative incidence of implantable cardioverter defibrillator (ICD) therapy at 7 years was 50, and death without ICD therapy was observed in 9 of patients. At least three comorbid conditions were observed in 81 of patients. Patients who died had a higher CCI score compared with those who survived (3.9 ± 1.5 vs. 2.9 ± 1.5; P < 0.001). An age-adjusted CCI score <5 was a predictor of mortality (hazard ratio 3.69, 95 CI 2.066.60; P < 0.001) independent from indication for ICD therapy, and from ICD interventions during the clinical course.ConclusionComorbidity is often present in heart failure patients, and a high comorbidity burden was a significant predictor of mortality in CRT-D recipients. Comorbidity cannot predict appropriate ICD therapy. Death without prior ICD therapy occurs in a minor proportion of patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010. For permissions please email: journals.permissionsoxfordjournals.org.2010The online version of this article has been published under an open access model. Users are entitled to use, reproduce, dissem

Aims The aim of this study was to determine the relationship between improved ejection fraction (EF) and occurrence of arrhythmias in patients with cardiac resynchronization therapy devices with defibrillator function (CRT-D). The hypothesis was that patients who experienced a marked improvement in EF also had fewer appropriate defibrillator interventions. Methods and results We analysed data of 270 patients from2 prospective registries with follow-up of ≥12 months and echocardiography performed ≥8 months after CRT-D implantation. The discriminator was whether left ventricular ejection fraction (LVEF) improved to >35 [cut-off for primary prevention implantable cardioverter-defibrillator (ICD) implantation]. Mean age was 61 ± 11 years, LVEF 22 ± 5, and follow-up 40 ± 22 months. Ischaemic cardiomyopathy was present in 48, and secondary prevention indication was present in 25. Implantable cardioverter-defibrillator interventions were delivered to 35 of patients. Echocardiography (20 ± 15 months after implantation) showed an improvement in LVEF from 22 (SD 5.4) to 30 (SD 9.8). Improvement to >35 was seen in 21 of patients. Those who improved to >35 had fewer ICD interventions than those who did not (23 vs.38; P-value 0.03). Analysing only patients with a primary prevention indication and stratifying again in patients with and without improvement of LVEF to >35, the latter had highly significant more ICD-therapies (6 vs. 31; P-value 0.0008).Conclusion Patients with CRT-D for primary prevention, whose LVEF improved to >35 during mid-term follow-up, are at low risk of first ICD therapies beyond year 1. If similar findings are reported in other patient cohorts, this might impact on decision-making at the time of battery depletion.

The dynamic interaction between subendocardial and subepicardial fibre helices in the left ventricle (LV) leads to a twisting deformation, which has an important role in LV function. This study sought to assess the influence of cardiac shape on LV twist in the normal and dilated human heart. The study comprised 45 dilated cardiomyopathy (DCM) patients and 60 for age- and gender-matched healthy volunteers. Speckle tracking echocardiography was used to determine basal and apical LV peak systolic rotation (Rotmax) and instantaneous LV peak systolic twist (Twistmax). LV sphericity index was calculated by dividing the LV maximal long-axis internal dimension by the maximal short-axis internal dimension at end-diastole. A parabolic relation between the sphericity index and apical Rotmaxor Twistmaxwas identified in the total study population (R2= 0.56 and R2= 0.54, respectively; both P < 0.001) and healthy volunteers (R2= 0.39 and R2= 0.25, respectively; both P < 0.001), whereas these relations were linear in DCM patients (R2= 0.40 and R2= 0.43, respectively; both P < 0.001). In a multivariate analysis, LV sphericity index was the strongest independent predictor of apical Rotmaxand Twistmax. In conclusion, LV apical rotation and twist are significantly influenced by LV configuration. Taking the important function of LV twist into account, this finding highlights the vital influence of cardiac shape on LV systolic function. Copyright

Aims: Studies reporting improved left ventricular (LV) function of percutaneous skeletal myoblast (SkM) injection in patients with ischaemic cardiomyopathy had follow-up not exceeding 12 months, and did not include a control group. Our group has reported evidence for myoblast efficacy in the first five out of the 14 treated patients. The objective of the present evaluation was to assess if these effects were sustained at long-term follow-up. We compared function of patients treated with SkM 4 years earlier with a matched control group. Secondary endpoints included mortality, NYHA class, N-terminal pro-B-natriuretic peptide levels, incidence of arrhythmias, and quality of life. Methods and results: Fourteen patients with ischaemic cardiomyopathy who underwent SkM injection were compared with 28 non-randomized control patients matched for age, sex, location, and extent of myocardial infarction. Contrast echocardiography and tissue Doppler imaging (TDI) was performed to compare global and regional LV function. At 4-year follow-up, three patients (21%) had died in the treated group and 11 patients (39%) in the control group (P = 0.8). In the survivors, LV ejection fraction (EF) was 35 ± 10% and 37 ± 9% in the SkM group and 36 ± 8% and 36 ± 6% in the controls at baseline and 4 years follow-up, respectively (P = 0.96 between groups at follow-up). TDI-derived systolic velocity in the injected sites was 5.4 ± 1.8 cm/s in the SkM group when compared with 5.1 ± 1.6 cm/s in corresponding sites in the control group (P = 0.47). None of the secondary endpoints showed a difference between the groups. However, in the patients fitted with an internal cardioverter defibrillator, more arrhythmias leading to interventions occurred in the treated group than in the control group, 87% and 13%, respectively (P = 0.015). Conclusion: Percutaneous intramyocardial SkM injection in ischaemic cardiomyopathy has no sustained positive effect on resting global or regional LV function, respectively

The increasing number and proportion of aged individuals in the population warrants knowledge of normal physiological changes of left ventricular (LV) biomechanics with advancing age. LV twist describes the instantaneous circumferential motion of the apex with respect to the base of the heart and has an important role in LV ejection and filling. This study sought to investigate the biomechanics behind age-related changes in LV twist by determining a broad spectrum of LV rotation parameters in different age groups, using speckle tracking echocardiography (STE). The final study population consisted of 61 healthy volunteers (16-35 yr, n = 25; 36-55 yr, n = 23; 56-75 yr, n = 13; 31 men). LV peak systolic rotation during the isovolumic contraction phase (Rotearly), LV peak systolic rotation during ejection (Rotmax), instantaneous LV peak systolic twist (Twistmax), the time to Rotearly, Rotmax, and Twistmax, and rotational deformation delay (defined as the difference of time to basal Rotmaxand apical Rotmax) were determined by STE using QLAB Advanced Quantification Software (version 6.0; Philips, Best, The Netherlands). With increasing age, apical Rotmax(P < 0.05), time to apical Rotmax(P < 0.01), and Twistmax(P < 0.01) increased, whereas basal Rotearly(P < 0.001), time to basal Rotearly(P < 0.01), and rotational deformation delay (P < 0.05) decreased. Rotational deformation delay was significantly correlated to Twistmax(R2= 0.20, P < 0.05). In conclusion, Twistmaxincreased with aging, resulting from both increased apical Rotmaxand decreased rotational deformation delay between the apex and the base of the LV. This may explain the preservation of LV ejection fraction in the elderly. Copyright

Background: Noncompaction cardiomyopathy (NCCM) is a rare disorder with persistance of the embryonic pattern of myoarchitecture. NCCM is characterized by loosened, spongy myocardium associated with a high incidence of systolic and diastolic left ventricular (LV) dysfunction and heart failure (HF). It is known that LV dysfunction contributes to elevated left atrial (LA) and pulmonary vascular pressures, however atrial function has not been examined in NCCM. The objective of the present study was to assess LA systolic function characterized by LA ejection force (LAEF) in NCCM patients using real-time three-dimensional echocardiography (RT3DE) and to compare to control subjects. Methods: The study comprised 17 patients with an established diagnosis of NCCM and their results were compared to 17 healthy age-matched controls with no evidence of cardiovascular disease. Forty-one percent of NCCM patients were in NYHA functional class II/III HF. Previously proposed echocardiographic diagnostic criteria for NCCM were used. All patients underwent conventional two-dimensional echocardiography and RT3DE. LAEF was measured based on MA annulus diameter (LAEF3D-MAD) and area (LAEF3D-MAA) using RT3DE. Results: The presence and severity of mitral regurgitation were more frequent in NCCM patients than in control subjects. LV diameters and mitral annulus were significantly increased in NCCM patients. Compared with control subjects, both LAEF3D-MAD(3.8 ± 2.2 vs 2.3 ± 1.0 kdyne P < 0.05 and LAEF3D-MAA(12.7 ± 7.6 vs 4.9 ± 2.1 kdyne, P < 0.01) were significantly increased in NCCM patients. Conclusions: LAEF as a characteristic of LA systolic function is increased in NCC

Aim: Assessment of pulmonary valve (PV) and right ventricular outflow tract (RVOT) using real-time 3-dimensional echocardiography (RT3DE). Methods: Two-dimensional echocardiography (2DE) and RT3DE were performed in 50 patients with congenital heart disease (mean age 32 ± 9.5 years, 60% female). Measurements were obtained at parasternal views: short axis (PSAX) at aortic valve level and long axis (PLAX) with superior tilting. RT3DE visualization was evaluated by 4-point score (1: not visualized, 2: inadequate, 3: sufficient, and 4: excellent). Diameters of PV annulus (PVAD), and RVOT (RVOTD) were measured by both 2DE and RT3DE, while areas (PVAA) and (RVOTA) by RT3DE only. Results: By RT3DE, PV was visualized sufficiently in 68% and RVOTexcellently in 40%. PVAD and PVAA were measured in 88%. RVOTD and PVAD by 2DE at PLAX were significantly higher than PSAX (P < 0.0001) and lower than that by RT3DE (P < 0.001). Conclusion: RT3DE helps inRVOT and PV assessment adding more details supplemental to 2DE.

Background: Mitral annulus assessment is of great importance for the diagnosis and treatment of mitral valve disease. The present study sought to assess the value of real-time three-dimensional echocardiography for the assessment of true mitral annulus diameter (MAD). Methods: One hundred and fifty patients (mean age 38 ± 18 years) with adequate two-dimensional (2D) echocardiographic image quality underwent assessment of MAD2Dand MAD3D(with real-time three-dimensional echocardiography). In a subgroup of 30 patients true MAD was validated with magnetic resonance imaging (MRI). Results: There was a good interobserver agreement for MAD2D(mean difference = -0.25 ± 2.90 mm, agreement: -3.16, 2.66) and MAD3D(mean difference = 0.29 ± 2.03, agreement = -1.74, 2.32). Measurements of MAD2Dand MAD3Dwere well correlated (R = 0.81, P < 0.0001). However, MAD3Dwas significantly larger than MAD2D(3.7 ± 0.9 vs. 3.3 ± 0.8 cm, P < 0.0001). In the subgroup of 30 patients with MRI validation, MAD3Dand MADMRIwere significantly larger than MAD2D(3.3 ± 0.5 and 3.4 ± 0.5 cm vs. 2.9 ± 0.4 cm, both P < 0.001). There was no significant difference between MADMRIand MAD3D. Conclusion: MAD3Dcan be reliably measured and is superior to MAD2Din the assessment of true mitral annular size.

Aims: The current study sought to assess if pre-implantation lateral-to-septal delay (LSD) ≥60 ms assessed by spectral pulsed-wave myocardial tissue Doppler imaging (PW-TDI) could predict successful long-term outcome after cardiac resynchronization therapy (CRT). Methods and results Sixty patients (72% males, mean age 59 ± 10 years) who were referred for CRT according to the ACC/ESC guidelines were enrolled in the study. All patients underwent spectral PW-TDI before and 1 year after CRT. Two left ventricular (LV) dyssynchrony time intervals, TOand TP(time to onset and peak of LV myocardial velocity, respectively), LSD were recorded. Left ventricular dyssynchrony was defined as LSD ≥60 ms. Clinical response was defined as an improvement in >1 NYHA class plus improvement in 6-min walk distance (6MWD) ≥25%, echocardiographic response was defined as a ≥15% reduction in LV end-systolic volume (LV-ESV). One year after CRT, 50 patients (83%) were clinical responders and 47 patients (78%) were echocardiographic responders. Both TOand TPLV dyssynchrony indices failed to predict echocardiographic CRT outcome. In addition, there were no significant differences between 'synchronous' and 'dyssynchronous' patient populations at baseline or follow-up in either clinical (NYHA class and 6MWD) or echocardiographic (LV ejection fraction, LV end-diastolic, and end-systolic) variables. Conclusion: The great majority of patients referred for CRT benefit clinically from it. However, spectral PW-TDI

Background: The tricuspid valve (TV) is a complex structure. Unlike the aortic and mitral valve it is not possible to visualize all TV leaflets simultaneously in one cross-sectional view by standard two-dimensional echocardiography (2DE) either transthoracic or transesophageal due to the position of TV in the far field. Aim: Quantitative and qualitative assessment of the normal TV using real-time 3-dimensional echocardiography (RT3DE). Methods: RT3DE was performed for 100 normal adults (mean age 30 ± 9 years, 65% males). RT3DE visualization was evaluated by 4-point score (1: not visualized, 2: inadequate, 3: sufficient, and 4: excellent). Measurements included TV annulus diameters (TAD), TV area (TVA), and commissural width. Results: In 90% of patients with good 2DE image quality, it was possible to analyse TV anatomy by RT3DE. A detailed anatomical structure including unique description and measurement of tricuspid annulus shape and size, TV leaflets shape, and mobility, and TV commissural width were obtained in majority of patients. Identification of each TV leaflet as seen in the routine 2DE views was obtained. Conclusion: RT3DE of the TVis feasible in a large number of patients. RT3DE may add to functional 2DE data in description of TV anatomy and providing highly reproducible and actual reality (anatomical and functional) measurements.

Aim: To detect the accuracy of real-time three-dimensional echocardiography (RT3DE) and two-dimensional echocardiography (2DE) for tricuspid annulus (TA) assessment compared with magnetic resonance imaging (MRI). Methods: Thirty patients (mean age 34 ± 13 years, 60% males) in sinus rhythm were examined by MRI, RT3DE, and 2DE for TA assessment. End-diastolic and end-systolic TA diameter (TAD) and TA fractional shortening (TAFS) were measured by RT3DE, 2DE, and MRI. End-diastolic and end-systolic TA area (TAA) and TA fractional area changes (TAFAC) were measured by RT3DE and MRI. End-diastolic and end-systolic right ventricular (RV) volumes and ejection fraction (RV-EF) were measured by MRI. Results: The TA was clearly delineated in all patients and visualized as an oval-shaped by RT3DE and MRI. There was a good correlation between TADMRIand TAD3D(r = 0.75, P = 0.001), while TAD2Dwas fairly correlated with TAD3Dand TADMRI(r = 0.5, P = 0.01 for both). There were no significant differences between RT3DE and MRI in TAD, TAA, TAFS, and TAFAC measurements, while TAD2Dand TAFS2Dwere significantly underestimated (P < 0.001). TAFS2Dwas not correlated with RV-EF, while TAFS3Dand TAFAC3Dwere fairly correlated with RV-EF (r = 0.49, P = 0.01, and r = 0.47, P = 0.02 respectively). Conclusion: RT3DE helps in accurate assessment of TA comparable to MRI and may have an important implication in the TV surgical decision-making processes. RT3DE analysis of TA function could be used as a marker of RV function.

Background: Cardiac involvement in mucopolysaccharidosis type I (MPS I) has been studied primarily in its most severe forms. Cardiac involvement, particularly left ventricular (LV) systolic and diastolic function, in the attenuated form of MPS I is less well known. Methods: Cardiac function was prospectively investigated in 9 adult patients with the attenuated form of MPS I. All patients underwent 12-lead electrocardiography, 24 h Holter monitoring and two-dimensional echocardiography including tissue Doppler imaging (TDI). Eighteen age- and sex-matched healthy volunteers served as a control group. Results: Aortic, mitral and tricuspid valve thickening was seen in, respectively, 5 (56%), 4 (44%) and 2 (22%) patients. Moderate mitral valve stenosis was seen in 1 patient and moderate aortic stenosis in 2 patients. All patients had mild-to-moderate aortic and mitral valve regurgitation and 6 patients (67%) had mild-to-moderate tricuspid valve regurgitation. Despite normal LV dimensions, ejection fraction and mass index, MPS patients had lower mean systolic mitral annular velocities (6.1±0.6 vs 9.1±1.4 cm/s, p<0.01) compared to normal control subjects. Similarly, mean early diastolic mitral annular velocities were lower in MPS patients (7.8±0.9 vs 13.3±3.3 cm/s, p<0.01). Conclusion: MPS I patients with the attenuated phenotype have not only valvular abnormalities but also LV diastolic and systolic abnormalities.

The aim of this thesis was to investigate the potential application of echocardiography for an efficient management of heart failure (HF) patients. The thesis is presented in four parts as follows: part I (introduction), part II (assessment of global left ventricular systolic function), part III (assessment of cardiac resynchronization therapy), and part IV (summary and conclusion). The general introduction (Chapter 1) of this thesis provides an overview of HF management using cardiac resynchronization therapy (CRT). HF constitutes an increasing and prevalent health burden worldwide. Echocardiography is a versatile non-invasive imaging modality that can be used for an efficient management of HF by proper diagnosis and guiding therapeutic interventions. Accurate assessment of left ventricular (LV) volumes and ejection fraction (LV-EF) would have important prognostic implications. CRT is a technique in which atrio-biventricular pacing is used to improve clinical and echocardiographic outcome for selected HF patients. The rationale behind CRT is the restoration of atrio-ventricular, inter-ventricular and intra-ventricular synchrony by stimulation of the delayed ventricular sites. It results in effective LV filling and emptying, reducing ventricular size improving ventricular geometry and most importantly improves survival. However, these impressive results of CRT are not seen in ~30% of patients. There are several unresolved and potentially other undetected reasons behind the high percentage of CRT failure. The echocardiography may improve the efficacy of CRT by reducing the non –response rate. The potential fields of echocardiography are: proper selection of candidates; optimization of atrio- and inter-ventricular pacing; guiding lead placement and proper detection of the response to CRT by accurate assessment of atrial and ventricular structure and function. These fields are mostly the topics of this thesis.

Aortic stiffness is an important predictor of cardiovascular morbidity and mortality. Non-invasive measurement of aortic stiffne

Recently, debate has erupted about the clinical significance of cardiovascular shunts. Several major health problems such as stroke and migraine have been associated with patent foramen ovale (PFO) with right-to-left shunt (RLS). The nature of the relationship between these syndromes and PFO is not clearly understood. Technical advances have led to more therapeutic options including device closure of PFO, hence prevention of such a PFO-related stroke has become feasible. Therefore, optimal diagnosis of PFO has become of greater clinical importance. Contrast echocardiography with non-transpulmonary contrast agents has been the cornerstone in diagnosis of PFO with RLS for over four decades. Despite being a relatively invasive procedure, transesophageal echocardiography (TEE) is considered the gold standard for detection of RLS. Several other echocardiographic techniques such as transthoracic echocardiography (TTE) with second harmonic imaging and transcranial Doppler ultrasonography (TCD) have shown increased sensitivity and specificity compared to TEE for the detection of PFO with RLS. Moreover, improvement of skills and techniques used for detection of these shunts has led to greater detection of small and large sized RLS in the echocardiographic laboratory. This review gives and overview of the echocardiographic techniques, contrast agents and manoeuvres used for detection of the major cardiovascular shunts and their clinical relevance to major health problems.

Cardiac hydatid disease or echinococcosis is a rare complication of Echinococcus granulosus infection. Traditionally, the diagnosis is made with two-dimensional transthoracic echocardiography. This case report shows the complementary function of the different echo modalities (two-dimensional, three-dimensional, and contrast echocardiography) and MRI in the evaluation of pericardial hydatid cyst.