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Aim To determine the feasibility and potential benefit of a full cardiac magnetic resonance (CMR) work-up for assessing the location of scarred myocardium and the region of latest contraction (LCR) in patients with ischaemic cardiomyopathy (ICM) undergoing cardiac resynchronisation therapy (CRT). Methods In 30 patients, scar identification and contraction timing analysis was retrospectively performed on CMR images. Fluoroscopic left ventricular (LV) lead positions were scored with respect to scar location, and when placed outside scar, with respect to the LCR. The association between the lead position with respect to scar, the LCR and echocardiographic LV end-systolic volume (LVESV) reduction was subsequently evaluated. Results The CMR work-up was feasible in all but one patient, in whom image quality was poor. Scar and contraction timing data were succesfully displayed on 36-segment cardiac bullseye plots. Patients with leads placed outside scar had larger LVESV reduction (−21 ± 21%, n = 19) compared to patients with leads within scar (1 ± 25%, n = 11), yet total scar burden was higher in the latter group. There was a trend towards larger LVESV reduction in patients with leads in the scar-free LCR, compared to leads situated in scar-free segments but not in the LCR (−34 ± 14% vs −15 ± 21%, p = 0.06). Conclusions The degree of reverse remodelling was larger in patients with leads situated in a scar-free LCR. In patients with leads situated within scar there was a neutral effect on reverse remodelling, which can be caused both by higher scar burden or lead position. These findings demonstrate the feasibility of a CMR work-up and potential benefit in ICM patients undergoing CRT.

This study evaluated the acute effect of dP/dtHemodynamic optimization may increase benefit from CRT. Typically, maximal left ventricular (LV) pressure rise dP/dtForty-one patients underwent CRT implantation followed by invasive PV loop measurements. The stimulation protocol included 16 LV pacing configurations using each individual electrode of the quadripolar lead with 4 atrioventricular (AV) delays. Conventional CRT was defined as pacing from the distal electrode with an AV delay of approximately 120 ms.Compared with conventional CRT, dP/dtPV-guided hemodynamic optimization in CRT results in approximately one-third SW improvement on top of conventional CRT, caused by a mechanism of enhanced VA coupling. In contrast, dP/dt

Arrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease clinically characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. Current electrocardiographic and structural imaging methods fail to detect early-stage AC-related myocardial disease in mutation carriers. Here, we propose a cardiac imaging-based personalized modelling approach that enables the identification and characterization of regional electro-mechanical tissue abnormalities in the vulnerable right ventricular (RV) free wall of AC mutation carriers. RV tissue deformation data from 2 controls and 8 mutation carriers, covering various stages of AC disease, were used to personalize the Circ.Adapt model of the human heart and circulation. This resulted in estimates of contractility and stiffness in the apical, midventricular, and basal segments of the RV. Apex-to-base heterogeneity in tissue properties, with increased stiffness and decreased contractility in the RV basal region, was found in most patients and was largest in late-stage AC disease. Future studies should evaluate whether early-stage tissue heterogeneity is predictive for arrhythmic events or AC disease progression.

Objective: The relation between different electrocardiographic left ventricular hypertrophy (ECG-LVH) criteria and cardiovascular risk in patients with clinical manifest arterial disease is unclear. Therefore, we determined the association between four ECG-LVH criteria: Sokolow-Lyon, Cornell product, Cornell/strain index and Framingham criterion; and risk of cardiovascular events and mortality in this population. Methods: Risk of cardiovascular events was estimated in 6913 adult patients with clinical manifest arterial disease originating from the Secondary Manifestations of ARTerial disease (SMART) cohort. Cox proportional regression analysis was used to estimate the risk of the four ECG-LVH criteria and the primary composite outcome: myocardial infarction (MI), stroke or cardiovascular death; and secondary outcomes: MI, stroke and all-cause mortality; adjusted for confounders. Results: The highest prevalence of ECG-LVH was observed for Cornell product (10%) and Cornell/strain index (9%). All four ECG-LVH criteria were associated with an increased risk of the primary composite endpoint: Sokolow-Lyon (hazard ratio 1.37, 95% CI 1.13-1.66), Cornell product (hazard ratio 1.54, 95% CI 1.30-1.82), Cornell/strain index (hazard ratio 1.70, 95% CI 1.44-2.00) and Framingham criterion (hazard ratio 1.78, 95% CI 1.21-2.62). Cornell product, Cornell/strain index and Framingham criterion ECG-LVH were additionally associated with an elevated risk of secondary outcomes. Cardiovascular risk increased whenever two, or three or more ECG-LVH criteria were present concurrently. Conclusion: All four ECG-LVH criteria are associated with an increased risk of cardiovascular events. As Cornell/strain index is both highly prevalent and carries a high cardiovascular risk, this is likely the most relevant ECG-LVH criterion for clinical practice.

Recent advances in the early detection and treatment of cancer have led to increasing numbers of cancer survivors worldwide. Nonetheless, despite major improvements in the outcome of these patients, long-term side effects of radio- and chemotherapy affect both patient survival and quality of life, independent of the oncological prognosis. Chemotherapy-related cardiac dysfunction is one of the most notorious short-term side effects of anticancer treatment, occurring in ~10% of patients. Progression to overt heart failure carries a strikingly poor prognosis with a 2-year mortality rate of 60%. Early detection of left ventricular damage by periodic monitoring and prompt initiation of heart failure treatment is key in improving cardiovascular prognosis. To meet the growing demand for a specialised interdisciplinary approach for the prevention and management of cardiovascular complications induced by cancer treatment, a new discipline termed cardio-oncology has evolved. However, an uniform, multidisciplinary approach is currently lacking in the Netherlands. This overview provides an introduction and comprehensive summary of this emerging discipline and offers a practical strategy for the outpatient management of this specific patient population. Electronic supplementary material The online version of this article (10.1007/s12471-018-1148-7) contains supplementary material, which is available to authorized users.

Background In patients with vascular disease, risk models may support decision making on novel risk reducing interventions, such as proprotein convertase subtilisin/kexin type 9 inhibitors or anti‐inflammatory agents. We developed and validated an innovative model to estimate life expectancy without recurrent cardiovascular events for individuals with coronary, cerebrovascular, and/or peripheral artery disease that enables estimation of preventive treatment effect in lifetime gained. Methods and Results Study participants originated from prospective cohort studies: the SMART (Secondary Manifestations of Arterial Disease) cohort and REACH (Reduction of Atherothrombosis for Continued Health) cohorts of 14 259 ( REACH Western Europe), 19 170 ( REACH North America) and 6959 ( SMART , The Netherlands) patients with cardiovascular disease. The SMART‐REACH model to estimate life expectancy without recurrent events was developed in REACH Western Europe as a Fine and Gray competing risk model incorporating cardiovascular risk factors. Validation was performed in REACH North America and SMART . Outcomes were (1) cardiovascular events (myocardial infarction, stroke, cardiovascular death) and (2) noncardiovascular death. Predictors were sex, smoking, diabetes mellitus, systolic blood pressure, total cholesterol, creatinine, number of cardiovascular disease locations, atrial fibrillation, and heart failure. Calibration plots showed high agreement between estimated and observed prognosis in SMART and REACH North America. C‐statistics were 0.68 (95% confidence interval, 0.67–0.70) in SMART and 0.67 (95% confidence interval, 0.66–0.68) in REACH North America. Performance of the SMART‐REACH model was better compared with existing risk scores and adds the possibility of estimating lifetime gained by novel therapies. Conclusions The externally validated SMART‐REACH model could be used for estimation of anticipated improvements in life expectancy without recurrent cardiovascular events in individual patients with cardiovascular disease in Western Europe and North America.

The purpose of this study was to evaluate mitral regurgitation (MR) severity in patients undergoing transcatheter aortic valve replacement (TAVR) by standardized assessment of two-dimensional (2D) transthoracic echocardiography (TTE) and 1-year echocardiographic and clinical outcomes. Pre- and post-procedural TTE’s of patients undergoing TAVR between 2008 and 2014 were analyzed. MR was graded according to current guidelines with a systematic and integrated approach. Longitudinal echocardiographic and clinical results were analyzed. Regression analysis was performed for change in MR grade at follow-up, using pre-determined variables and confounders. Pre- and post-procedural TTE were available in 213 subjects. Significant MR was seen in 22% at baseline and 15% at follow-up; MR grade ≥ 3 in < 10%. Severity did not change in 61%, and decreased in 20% of the patients. Overall, the prevalence of MR grades pre- and post TAVR was not significantly different, nor influenced by MR etiology or TAVR prosthesis type. However, higher MR grades and pacemaker absence at baseline, were independently correlated to more improvement of MR after TAVR. Regarding clinical outcomes, NYHA class improved in two-thirds of the patients, irrespective of the baseline MR grade. Overall survival was not significantly different amongst MR grades post-TAVR. MR grading using an systematic 2D echocardiographic approach in patients undergoing TAVR is feasible in clinical practice. Our data revealed a relatively frequent prevalence of significant MR (although grade ≥ 3 was scarce), overall no change in the MR grade at 1 year follow-up, improvement of functional NYHA class, and no significant differences in long-term survival amongst the post-TAVR MR grades.

Background Stress echocardiography (SE) has recently regained momentum as an important diagnostic tool for the assessment of both ischemic and non-ischemic heart disease. Performing SE during physical exercise is challenging due to a suboptimal patient position and vigorous movements of the patient’s chest. This hampers a stable ultrasound position and reduces the diagnostic performance of SE. A stable ultrasound probe position would facilitate producing high quality images during continuous measurements. With Probefix (Usono, Eindhoven, The Netherlands), a newly developed tool to fixate the ultrasound probe to the patient’s chest, stabilization of the probe during physical exercise is possible. Implementation and results The technique of SE with the Probefix and its’ feasibility are evaluated in a small pilot study. Probefix fixates the ultrasound probe to the patient’s chest, using two chest straps and a fixation device. The ultrasound probe position and angle may be altered with a relative high degree of freedom. We tested the Probefix for continuous echocardiographic imaging in 12 study subjects during supine and upright ergometer stress tests. One patient was unable to perform exercise and in two study subjects good quality images were not achieved. In the other patients (82%) a stable probe position was obtained, with subsequent good quality echocardiographic images during SE. Conclusion We have demonstrated the feasibility of the Probefix support during ergometer tests in supine and upright positions and conclude that this external fixator may facilitate continuous monitoring of cardiac function in a group of patients. Electronic supplementary material The online version of this article (10.1186/s12947-018-0124-0) contains supplementary material, which is available to authorized users.

BackgroundClinical decision-making in symptomatic patients after mitral valve (MV) repair remains challenging as echocardiographic reference values are lacking. In native MV disease intervention is recommended for mean transmitral pressure gradient (TPG) >15 mmHg or systolic pulmonary artery pressure (SPAP) >60 mmHg at peak exercise. Insight into standard stress echo parameters after MV repair may therefore aid to clinical decision-making during follow-up.HypothesisStress echocardiography derived parameters in asymptomatic patients after successful MV repair differ from current guidelines for native valves.Material and methodsIn 25 patients (NYHA I) after MV repair stress echocardiography was performed on a semi-supine bicycle. Doppler flow records and MV related hemodynamics at rest and peak were obtained. Linear regression analysis was performed for mean TPG and SPAP at peak, using predetermined variables and confounders.ResultsMean TPG at rest (3.2 ± 1.4 mmHg) significantly increased at peak (15.0 ± 3.4 mmHg) but was always 57 mmHg. Only the indexed MV ring diameter was inversely correlated to mean TPG at peak in a multivariable model.ConclusionIn contrast to current recommendations in native MV disease, our data indicate that the standard value for mean TPG during stress echocardiography in asymptomatic patients after successful MV repair was above the guideline threshold of 15 mmHg in >50%, but always

Background: Among patients with clinically manifest vascular disease, the risk of recurrent vascular events is likely to vary. We assessed the distribution of estimated 10-year risk of recurrent vascular events in a secondary prevention population. We also estimated the potential risk reduction and residual risk that can be achieved if patients reach guideline-recommended risk factor targets. Methods: The SMART score (Second Manifestations of Arterial Disease) for 10-year risk of myocardial infarction, stroke, or vascular death was applied to 6904 patients with vascular disease. The risk score was externally validated in 18 436 patients with various manifestations of vascular disease from the TNT (Treating to New Targets), IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering), SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), and CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trials. The residual risk at guideline-recommended targets was estimated by applying relative risk reductions from meta-analyses to the estimated risk for targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, and use of antithrombotic agents. Results: The external performance of the SMART risk score was reasonable, apart from overestimation of risk in patients with 10-year risk >40%. In patients with various manifestations of vascular disease, median 10-year risk of a recurrent major vascular event was 17% (interquartile range, 11%–28%), varying from 30% in 22% of the patients. If risk factors were at guideline-recommended targets, the residual 10-year risk would be 30% in 9% of the patients (median, 11%; interquartile range, 7%–17%). Conclusions: Among patients with vascular disease, there is very substantial variation in estimated 10-year risk of recurrent vascular events. If all modifiable risk factors were at guideline-recommended targets, half of the patients would have a 10-year risk 20% and even >30% 10-year risk, clearly delineating an area of substantial unmet medical need.

Item does not contain fulltext Newly developed treatment strategies for breast cancer have reduced mortality rates over the past decades. Patients with breast cancer represent a heterogeneous population. Differences in the severity of the disease require diverse treatment options. Women have distinct individual risk patterns for cardiovascular disease that may affect their susceptibility to cardiotoxicity during therapy. While breast cancer treatment is targeted more on tumor and patient characteristics, a tailored individual approach with early and late cardiosurveillance is not yet implemented in routine care. Newly available cardiac imaging techniques are better suited to the early detection of cardiotoxicity and should be used more often in those patients at highest risk, as the early intervention afforded will improve their quality of life and prognosis.

Objective The objective of the study was to examine whether cardiac resynchronisation therapy upgrade procedures are more complex and associated with more complications than de novo implantations. Method We retrospectively compared 134 upgrade procedures performed between 2006–2012 with a random, equally sized, sample of de novo CRT device implantations in the same period. Procedural data and the occurrence of periprocedural (≤ 30 days) and long-term device-related (≤ 1 year) complications were analysed. Complications with consequences were defined as those in need of adjustment of standard care. Results Median time to upgrade was 57 (31–115) months. There were no significant differences in procedure duration, radiation time or total hospitalisation between upgrades and de novo implantations. Perioperative complications occurred in 6.7 % of upgrade patients and in 9.0 % of de novo patients. The most frequently seen complications were phrenic nerve stimulation, coronary sinus dissection and pocket haematoma. Procedure success was comparable (upgrade: 98.5 % versus de novo: 96.3 %). A total of 236 patients completed 1 year of follow-up. Ten (4.2 %) patients had a long-term device-related complication with consequences including phrenic nerve stimulation, lead dislodgement/dysfunction, and infection (upgrade: 3.5 % versus de novo: 4.9 %). Conclusion Upgrade procedures are not more complex nor associated with more complications than de novo CRT implantations.

Introduction Predicting reverse remodeling after cardiac resynchronization therapy (CRT) remains challenging and different etiologies of heart failure might hamper identification of predictors. Objective Assess the incremental value of mechanical dyssynchrony besides electrical dyssynchrony for predicting CRT response. Methods 227 patients (51% ischemic) received CRT. Response was defined as ≥ 15% left ventricular end systolic volume decrease after six months. Prediction models were developed comprising clinical parameters and electrical dyssynchrony (Model A), subsequently complemented with mechanical dyssynchrony (Model B). Models were compared by area under the receiver-operating curve (AUC), net reclassification index (NRI) and integrated discrimination improvement (IDI) for the complete cohort, ischemic (ICM) and non-ischemic (NICM) subpopulations. Results Model B performed significantly better than Model A supported by AUC, NRI and IDI. Furthermore, model B significantly better predicted response for NICM than ICM. Conclusion Electrical dyssynchrony and mechanical dyssynchrony are essential to predict CRT response. Nevertheless, response prediction for ICM remains challenging.

ObjectivePresentations of non-cardiac chest pain (NCCP) to the emergency department (ED) are increasing. More knowledge of prognosis and healthcare utilisation of patients with NCCP is necessary to optimise their management.MethodsThis study is a prospective, observational, prevalence-based cohort study conducted from September 2015 to February 2016 with 1-year follow-up including all patients 18 years and older referred to the ED with chest pain. Discharge diagnoses, mortality, major adverse cardiac events (MACE), re-presentations to the ED, hospitalisations, cardiac interventions and outpatient monitoring were assessed.ResultsMore than 60% of the 1239 patients presenting with chest pain were discharged with NCCP. The all-cause 1-year mortality rate of patients with NCCP was 2.3% compared with 7.2% in patients with cardiac chest pain (CCP) (pConclusionThe majority of patients referred to the ED with chest pain are discharged with NCCP. The prognosis of patients with NCCP is better than patients with CCP; however, they are at risk for MACE due to a history of CAD. Patients with NCCP moreover use a substantial amount of medical resources, stressing the importance of good triage to minimise unnecessary healthcare utilisation while still preventing MACE.

Chemotherapy-related cardiac dysfunction is a significant side effect of anticancer treatment. Risk stratification is based on clinical- and treatment-related risk factors that do not adequately explain individual susceptibility. The addition of genetic variants may improve risk assessment. We conducted a systematic literature search in PubMed and Embase, to identify studies investigating genetic risk factors for chemotherapy-related cardiac dysfunction. Included were articles describing genetic variants in humans altering susceptibility to chemotherapy-related cardiac dysfunction. The validity of identified studies was assessed by 10 criteria, including assessment of population stratification, statistical methodology, and replication of findings. We identified 40 studies: 34 exploring genetic risk factors for anthracycline-induced cardiotoxicity (n=9678) and 6 studies related to trastuzumab-associated cardiotoxicity (n=642). The majority (35/40) of studies had a candidate gene approach, whereas 5 genome-wide association studies have been performed. We identified 25 genetic variants in 20 genes and 2 intergenic variants reported significant at least once. The overall validity of studies was limited, with small cohorts, failure to assess population ancestry and lack of replication. SNPs with the most robust evidence up to this point areCELF4rs1786814 (sarcomere structure and function),RARGrs2229774 (topoisomerase-2β expression),SLC28A3rs7853758 (drug transport),UGT1A6rs17863783 (drug metabolism), and 1 intergenic variant (rs28714259). Existing evidence supports the hypothesis that genetic variation contributes to chemotherapy-related cardiac dysfunction. Although many variants identified by this systematic review show potential to improve risk stratification, future studies are necessary for validation and assessment of their value in a diagnostic and prognostic setting.

Objective Diabetes mellitus is associated with an increased risk for cardiovascular morbidity and mortality. The vascular burden in terms of incidence of cardiovascular events (CVE) and vascular interventions is however poorly quantified. In this study we evaluated the incidence rates of CVE and vascular interventions in patients with type 2 diabetes (T2DM) with and without cardiovascular disease (CVD) in comparison to patients without type 2 diabetes. Research design and methods In a cohort of 9.808 high-risk patients with and without cardiovascular disease and type 2 diabetes originated from the ongoing, single-center prospective SMART (Second Manifestations of ARTerial disease) cohort, the number and incidence rates of CVE and interventions were calculated. The incidence rates were adjusted for confounders using Poisson regression models. CVE were defined as vascular death, stroke and myocardial infarction (MI). Interventions were defined as percutaneous coronary intervention, coronary artery bypass grafting, percutaneous transluminal angioplasty or stenting of the peripheral arteries and amputation. Results Patients with T2DM and CVD had a 4-fold higher incidence rate of CVE and a 8-fold higher incidence rate of vascular interventions compared to high-risk patients without T2DM and CVD after adjusting for confounders. The incidence rate for the composite of non-fatal MI, non-fatal stroke and vascular death was 5.8 per 1000person-years in patients without T2DM or CVD at baseline, 15.2 per 1000person-years in patients with T2DM but without CVD at baseline, 26.0 per 1000person-years in patients without T2DM but with CVD and 40.7 per 1000person-years in patients with both T2DM and CVD at baseline. A similar increasing incidence rate was seen for all vascular interventions from patients without T2DM or CVD to patients with both T2DM and CVD. Conclusions Patients with type 2 diabetes or CVD are subject to an increased incidence of cardiovascular events and interventions compared to high-risk patients without type 2 diabetes or vascular disease. Patients with type 2 diabetes and CVD have the highest incidence of new cardiovascular diseases and vascular interventions when compared to patients without type 2 diabetes and CVD. These results underline the need for optimal risk factor treatment as well as the need for new prevention and treatment strategies in this very high risk population.

Purpose Mitral regurgitation (MR) grading by two-dimensional transthoracic echocardiography is challenging, but important to determine the best treatment strategy in patients with MR. Current guidelines advocate an integrative approach, although no recommendation is provided on how to do so. An easy-to-use index will be helpful for standardized and reproducible MR grading. Methods Eleven echocardiographic parameters were retrospectively evaluated in 145 patients with moderate or severe MR. Parameters were scored positive or negative for severe MR, where expert panel consensus reading was considered as the reference standard. Logistic regression was performed, and adjusted coefficients were used to create a risk score for severe MR per patient (ROSE-index). The best cutoff with corresponding predictive values was determined. Results Eighty-two percent of all parameters could be determined. Multivariable analysis revealed five parameters that remained significant predictors for severe MR: morphology, jet characteristics, vena contracta, systolic reversal, and left ventricular dimensions. With different weighing, a total score of 8 could be obtained. Median total ROSE-index score for moderate (2.0) and severe MR (5.0) did significantly differ. The cutoff score (≥4) revealed sensitivity 0.84 and specificity 0.83 to diagnose severe MR. Negative predictive value was 100% for score 0 and 1; score 6–8 showed a 100% positive predictive value. Inter- and intra-observer agreements were excellent (K-values >0.80). Conclusion Here, we propose an easy-to-use tool for integrated analysis of guideline parameters to assess MR severity. Using this so-called ROSE-index revealed reliable and reproducible assessment of severe MR (cutoff≥4) that may be helpful for clinical decision making.

Right ventricular (RV) dysfunction is a strong predictor of outcome in heart failure and is a key determinant of exercise capacity. Despite these crucial findings, the RV remains understudied in the clinical, experimental, and computer modelling literature. This review outlines how recent advances in using computer modelling and cardiac imaging synergistically help to understand RV function in health and disease. We begin by highlighting the complexity of interactions that make modelling the RV both challenging and necessary, and then summarize the multiscale modelling approaches used to date to simulate RV pump function in the context of these interactions. We go on to demonstrate how these modelling approaches in combination with cardiac imaging have improved understanding of RV pump function in pulmonary arterial hypertension, arrhythmogenic right ventricular cardiomyopathy, dyssynchronous heart failure and cardiac resynchronization therapy, hypoplastic left heart syndrome, and repaired tetralogy of Fallot. We conclude with a perspective on key issues to be addressed by computational models of the RV in the near future.

Left ventricular volume-time curves (VTCs) provide hemodynamic data, and may help clinical decision making. The generation of VTCs using echocardiography, however, is time-consuming and prone to inter-operator variability. In this study, we used a new non-invasive, operator-independent technique, the hemodynamic cardiac profiler (HCP), to generate VTCs. The HCP, which uses a low-intensity, patient-safe, high-frequency applied AC current, and 12 standard ECG electrodes attached on the thorax in a pre-defined pattern, was applied to five young healthy volunteers, five older healthy volunteers, and five patients with severe mitral regurgitation. From the VTCs generated by the HCP, the presence or absence of an isovolumetric contraction phase (ICP) was assessed, as well as the left ventricular ejection time (LVET), time of the pre-ejection period (tPEP), and ratio of the volumes of the early (E) and late (A) diastolic filling (E V/A V ratio), and compared to 2D transthoracic echocardiography (2D TTE) at rest. The reproducibility by two different operators showed good results (RMS = 5.2%). For intra-patient measurement RMS was 2.8%. Both LVET and the E V/A V ratio showed a strong significant correlation between HCP and 2D TTE derived parameters (p < 0.05). For tPEP, the correlation was still weak (p = 0.32). In all five patients with mitral regurgitation, the ICP was absent in the VTC from the HCP, whereas it was present in the 10 healthy volunteers, which is in accordance with pathophysiology. We conclude that the HCP seems to be a method for reproducible VTC generation, and may become a useful early screening tool for cardiac dysfunction in the future.

A total of 581 consecutive patients from 21 primary care practices in The Netherlands with type 2 diabetes, in whom the diagnosis of heart failure (HF) was not known, underwent an extensive diagnostic assessment, including medical history taking, physical examination, ECG, and echocardiography. The presence or absence of HF was established by a panel of two cardiologists and one general practitioner following the guidelines on HF of the European Society of Cardiology. In 161 patients, HF was considered present. A model based on the medical history and symptoms had a good discriminative value for detecting or excluding HF [C-statistic after bootstrapping 0.80; 95% confidence interval (CI) 0.76–0.83]. Adding signs improved the C-statistic to 0.82 (95% CI 0.79–0.86). A diagnostic screening score based on the clinical model had good discriminative properties applying a cut-off of 3 points (24.7% risk of HF) with sensitivity 70.8%, specificity 79.0%, negative predictive value 87.6%, and positive predictive value 56.4%. ECG and natriuretic peptides both had independent added value beyond the clinical model and increased the C-statistic to 0.86 (95% CI 0.83– 0.89). With a 20% threshold, the net reclassification of adding ECG and NT-proBNP to the clinical model was only 0.06.

Postoperative new-onset atrial fibrillation (PNAF) is very common after cardiac surgery and postoperative inflammation may contribute to PNAF by inducing atrial dysfunction. Corticosteroids reduce inflammation and may thus reduce atrial dysfunction and PNAF development. This study aimed to determine whether dexamethasone protects against left atrial dysfunction and PNAF in cardiac surgical patients. Cardiac surgical patients were randomised to a single dose of dexamethasone (1 mg.kg(-1)) or placebo after inducing anaesthesia. Transoesophageal echocardiography was performed in patients before and after surgery. Primary outcome was left atrial total ejection fraction (LA-TEF) after sternal closure; secondary outcomes included left atrial diameter and PNAF. 62 patients were included. Baseline characteristics were well balanced. Postoperative LA-TEF was 36.4 % in the dexamethasone group and 40.2 % in the placebo group (difference -3.8 %; 95 % confidence interval (CI) -9.0 to 1.4 %; P = 0.15). Postoperative left atrial diameter was 4.6 and 4.3 cm, respectively (difference 0.3; 95 % CI -0.2 to 0.7; P = 0.19). The incidence of PNAF was 30 % in the dexamethasone group and 39 % in the placebo group (P = 0.47). Intraoperative high-dose dexamethasone did not protect against postoperative left atrial dysfunction and did not reduce the risk of PNAF in cardiac surgical patients.

Background: Reduced exercise tolerance and dyspnea are common in older people, and heart failure (HF) and chronic obstructive pulmonary disease (COPD) are the main causes. We want to determine the prevalence of previously unrecognized HF, COPD, and other chronic diseases in frail older people using a nearhome targeted screening strategy. Methods: Community-dwelling frail persons aged >65 years underwent a 2-step screening strategy. First, they received a questionnaire inquiring about dyspnea and exercise tolerance. Those with exercise intolerance and/or dyspnea were invited to visit their primary care physician’s office for a screening program, including medical history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. The final diagnosis of every patient was determined by a panel consisting of 3 physicians. Results:tk;2 Of the 570 elderly who filled out the questionnaire, 395 (69%) had reduced exercise tolerance or dyspnea. Of these, 389 underwent the screening program: 127 (33.5%, 95% confidence interval, 28.9 –38.4%) were newly diagnosed with HF (mainly HF with a preserved ejection fraction [23.5%]), and previously unrecognized COPD was detected in 16.8% (95% confidence interval, 13.4 – 20.9%). In total, 165 patients (43.9%) received a new diagnosis of either HF, COPD, or both. Other new diagnoses (in 32.7% of the screening program patients) included atrial fibrillation (1.8%), valvular disease (21.4%), (persisting) asthma (3.1%), anemia (12.7%), and thyroid disease (0.6%). No clear explanation for the complaints of 47 patients (12.2%) was found using our strategy. Conclusion: Unrecognized chronic diseases might be detected in community-dwelling frail elderly using a near-home screening strategy that is simple to implement. It remains to be proven, however, whether optimizing treatment of the newly detected diagnoses in this fragile population with multimorbidities and polypharmacy improves quality of life and reduces morbidity and mortality. (J Am Board Fam Med 2014;27:811– 821.)

Introduction: Rheumatic mitral stenosis continues to be prevalent in developing countries, notably in endemic areas. Over the last few decades, percutaneous balloon mitral valvuloplasty (PBMV) has been established as a lower-cost alternative treatment for mitral stenosis (MS) in low-to-middle-income countries. PBMV has also been suggested to be an effective and safe alternative treatment modality. This study aims to analyse the survival of rheumatic MS patients treated with PBMV compared with those treated with mitral valve surgery (MVS). Methods: This study was a national, single-centre, longitudinal study using a survival analysis method in 329 consecutive patients suffering from rheumatic heart disease with severe MS who underwent PBMV compared with 142 consecutive patients with similar characteristics who underwent MVS between January 2011 and December 2016. Survival analysis and event-free duration were determined over a median follow-up of 24 months in the PBMV group and 27 months in the MVS group. Results: The results showed that of the 329 consecutive patients in the PBMV group, 61 patients (18.5) had an event (6 patients died and 55 patients were hospitalised), and of the 142 consecutive patients in the MVS group, 19 patients (13.4%) had an event (5 patients died, and 14 patients were hospitalised). The hazard ratio was 0.631 (95% confidence interval, 0.376–1.058; P = 0.081). Longer short-term survival was found in the MVS group but was not statistically significant. Event-free survival was significantly longer in the MVS group (P = 0.002), by 5 months. Conclusions: In this study, the efficacy and safety of PBMV was reconfirmed, as PBMV proved to be non-inferior to MVS in survival prognosis, but sustained event-free duration was significantly better in the MVS group than in the PBMV group.

This study was performed to evaluate the feasibility of intra-procedural visualization of optimal pacing sites and image-guided left ventricular (LV) lead placement in cardiac resynchronization therapy (CRT). In fifteen patients (10 males, 68 ± 11 years, 7 with ischemic cardiomyopathy and ejection fraction of 26 ± 5%), optimal pacing sites were identified pre-procedurally using cardiac imaging. Cardiac magnetic resonance (CMR) derived scar and dyssynchrony maps were created for all patients. In six patients the anatomy of the left phrenic nerve (LPN) and coronary sinus ostium was assessed via a computed tomography (CT) scan. By overlaying the CMR and CT dataset onto live fluoroscopy, aforementioned structures were visualized during LV lead implantation. In the first nine patients, the platform was tested, yet, no real-time image-guidance was implemented. In the last six patients real-time image-guided LV lead placement was successfully executed. CRT implant and fluoroscopy times were similar to previous procedures and all leads were placed close to the target area but away from scarred myocardium and the LPN. Patients that received real-time image-guided LV lead implantation were paced closer to the target area compared to patients that did not receive real-time image-guidance (8 mm [IQR 0-22] vs 26 mm [IQR 17-46], p = 0.04), and displayed marked LV reverse remodeling at 6 months follow up with a mean LVESV change of -30 ± 10% and a mean LVEF improvement of 15 ± 5%. Real-time image-guided LV lead implantation is feasible and may prove useful for achieving the optimal LV lead position.

Background Previous studies demonstrated the prognostic importance of concomitant polyvascular disease in patients with coronary artery disease (CAD). However, the significance of the number of diseased vascular territories and subclinical disease is unknown. Materials and methods The number of diseased vascular territories was evaluated in 2299 percutaneous coronary intervention (PCI) patients. Vascular disease was defined by documented atherosclerotic disease, either diagnosed in the medical history (clinical) or at the standardized cardiovascular screening (subclinical). The following territories were evaluated: cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm and vascular renal disease. The outcome measures were all-cause mortality, cardiovascular mortality and a composite cardiovascular endpoint (myocardial infarction, stroke, cardiovascular mortality). Patients with monovascular disease (CAD) served as the reference category. Hazard ratios (HRs) were adjusted for baseline characteristics. Results Mean follow-up was 7·3 years. The HRs (95% confidence interval) for patients with two diseased territories compared to monovascular disease were for all-cause mortality 1·60 (1·14–2·25), cardiovascular mortality 2·13 (1·29–3·50) and the combined cardiovascular endpoint 1·66 (1·20–2·31). Moreover, the HRs (95% confidence intervals) for patients with more than two diseased territories compared to monovascular disease were for all-cause mortality 3·81 (2·45–5·92), cardiovascular mortality 4·40 (2·32–8·35) and the combined cardiovascular endpoint 2·75 (1·69–4·47). The HRs of patients with subclinical disease were comparable to the HRs of patients with clinical disease. Conclusions In patients undergoing PCI, the presence of subclinical and clinical polyvascular disease is associated with an increased long-term mortality and morbidity. Moreover, the outcome is highly influenced by the number of diseased territories.

OBJECTIVE: The objective of this study was to evaluate coronary image quality, stenosis grade, and diagnostic confidence in patients undergoing electrocardiogram-gated thoracoabdominal multidetector computed tomographic angiography (CTA) for aortic evaluation. METHODS: Seventy-five consecutive patients underwent retrospectively electrocardiogram-gated thoracoabdominal CTA reconstructed at each 12.5% of the R wave to R wave (R-R) interval. Two observers in consensus scored the coronary arteries per segment (15-segment American Heart Association model) for image quality, stenosis grade, and stenosis-assessment confidence. RESULTS: Nondiagnostic image quality prohibited coronary evaluation in 14 patients. In the remaining patients, 2% of segments was scored absent, 24% was scored nondiagnostic, 12% was scored diagnostically limited, and 61% was scored at least acceptable. Acceptable or higher image quality was seen in 82% of the proximal and middle segments. Significant stenosis (>50%) was seen in 57% of the patients. Stenosis-severity scoring confidence was moderate to high in 79% of 673 assessable segments. CONCLUSIONS: Electrocardiogram-gated thoracoabdominal CTA allows concomitant assessment of the proximal and middle coronary arteries and may serve as a combined tool for aortic-disease workup. Aortic CTA showed significant coronary artery stenosis in 57% of the patients evaluated for aortic pathology.

Aims The current study examined the degree of agreement between echocardiographic and patient-reported health status response to CRT 6 months after implantation, and evaluated the differences in pre-implantation characteristics of patients with concordant and discordant echocardiographic and health status responses. Methods and results Consecutively implanted CRT-defibrillator patients (n = 109, mean age = 65.4 ± 10.1 years, 74 men) were recruited from the University Medical Center Utrecht, The Netherlands. Prior to implantation and 6 months post-implantation, all patients underwent echocardiography and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ). Echocardiographic response was defined as a relative reduction of ≥15% in LV end-systolic volume; an improvement of ≥10 points in KCCQ score indicated a health status response. In the 54 patients with discordant responses, 25 (22.9%) had an echocardiographic response but no health status response and 29 (26.6%) had a health status response but no echocardiographic response. Patients with concordant and discordant responses differed on various pre-implantation characteristics, including sex, employment status, LV volumes, and pre-implantation KCCQ score. In multivariable analysis, pre-implantation KCCQ score [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.88–0.95, P

Purpose Exercise echocardiography can assess the dynamic component of mitral valve (MV) disease and may therefore be helpful for the clinical decision-making by the heart team. The purpose of this study is to determine the role of exercise echocardiography in the management of disproportionately symptomatic or otherwise atypical patients with mitral regurgitation (MR) and stenosis (MS) in clinical practice. Methods Data of 14 MR and 14 MS patients, including echocardiograms at rest, were presented retrospectively to an experienced heart team to determine treatment strategy. Subsequently, exercise echo data were provided whereupon once again the treatment strategy was determined. This resulted in: value of exercise echo by means of 1) alteration or 2) confirmation of treatment strategy or 3) no additional value. Results During exercise the echocardiographic severity of MV disease increased in 9 (64 %) MR and 8 (57 %) MS patients. Based upon alteration or confirmation of the treatment strategy, the value of exercise echocardiography in the management of MR and MS was 86 % and 57 %, respectively. Conclusion This study showed that physical exercise echo can have an important role in the clinical decision-making of challenging patients with MV disease. Exercise echocardiography had additional value to the treatment strategy in 71 % of these patients.

ARVD/C: The Triangle of Dysplasia Displaced Introduction The traditional description of the Triangle of Dysplasia in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) predates genetic testing and excludes biventricular phenotypes. Methods and Results We analyzed Cardiac Magnetic Resonance (CMR) studies of 74 mutation-positive ARVD/C patients for regional abnormalities on a 5-segment RV and 17-segment LV model. The location of electroanatomic endo- and epicardial scar and site of successful VT ablation was recorded in 11 ARVD/C subjects. Among 54/74 (73%) subjects with abnormal CMR, the RV was abnormal in almost all (96%), and 52% had biventricular involvement. Isolated LV abnormalities were uncommon (4%). Dyskinetic basal inferior wall (94%) was the most prevalent RV abnormality, followed by basal anterior wall (87%) dyskinesis. Subepicardial fat infiltration in the posterolateral LV (80%) was the most frequent LV abnormality. Similar to CMR data, voltage maps revealed scar (

Background This study investigated the prevalence of pulmonary hypertension (PH) in cystic fibrosis (CF) patients awaiting lung transplantation (LTx) and its influence on survival. We also explored the feasibility of using echocardiography as a first assessment for diagnosing PH. Methods The study included 93 CF patients (46 women [50%]) evaluated for LTx between 2001 and 2010. Median age was 29 years. PH was defined as a mean pulmonary artery pressure (mPAP) measured by right heart catheterization (mPAP cath ) of ≥ 25mm Hg with a wedge pressure of ≤ 15mm Hg. Echocardiographic results were divided into 3 categories based on current guidelines as "unlikely," "possible," or "likely" to have PH. Results In 23 patients (25%) the mPAP cath was between 25 and 35mm Hg, and 1 (1%) had severe PH (mPAP cath of ≥ 35mm Hg). PH did not influence survival after enlistment ( p = 0.7) and after LTx ( p = 0.8). For 62 patients (67%), the sPAP echo could be measured, and PH was unlikely in 24 (39%). In another 19 patients (20%), PH was unlikely based on the absence of tricuspid regurgitation. The negative-predictive value (NPV) of measuring PH by echocardiography was 88% in whom PH was estimated to be unlikely ( n = 43); whereas in 24 patients with a measurable low sPAP echo , the NPV was 96%. Conclusions PH exists in 26% of end-stage CF patients and has no effect on survival on the waiting list for LTx or after LTx. Echocardiography might be used as the first tool to rule out PH, showing a NPV of 88%.

Item does not contain fulltext The number of cancer survivors has tremendously increased over the past decades as a result of aging of the population and improvements in early cancer detection and treatment. Ongoing successes in cancer treatment are expected to result in a further increase in the number of long-term survivors. However, cancer treatment can have detrimental cardiovascular side-effects that impact morbidity and mortality, reducing quality of life in cancer survivors. The spectrum of radiotherapy- and chemotherapy-induced cardiovascular disease is broad, varying from subclinical valvular dysfunction to overt congestive heart failure, and such effects may not be apparent for more than twenty years after the initial cancer treatment. Awareness of these long-term side-effects is of crucial value in the management of these patients, in order to reduce the impact of cardiovascular morbidity and mortality. This review provides a comprehensive overview of the long-term cardiovascular complications of cancer treatments (radiotherapy and chemotherapy) in adult cancer survivors.

Item does not contain fulltext Background: The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score is an easy-to-apply instrument to stratify patients with chest pain according to their short-term risk for major adverse cardiac events (MACEs), but its effect on daily practice is unknown. Objective: To measure the effect of use of the HEART score on patient outcomes and use of health care resources. Design: Stepped-wedge, cluster randomized trial. (ClinicalTrials.gov: NCT01756846). Setting: Emergency departments in 9 Dutch hospitals. Patients: Unselected patients with chest pain presenting at emergency departments in 2013 and 2014. Intervention: All hospitals started with usual care. Every 6 weeks, 1 hospital was randomly assigned to switch to "HEART care," during which physicians calculated the HEART score to guide patient management. Measurements: For safety, a noninferiority margin of a 3.0% absolute increase in MACEs within 6 weeks was set. Other outcomes included use of health care resources, quality of life, and cost-effectiveness. Results: A total of 3648 patients were included (1827 receiving usual care and 1821 receiving HEART care). Six-week incidence of MACEs during HEART care was 1.3% lower than during usual care (upper limit of the 1-sided 95% CI, 2.1% [within the noninferiority margin of 3.0%]). In low-risk patients, incidence of MACEs was 2.0% (95% CI, 1.2% to 3.3%). No statistically significant differences in early discharge, readmissions, recurrent emergency department visits, outpatient visits, or visits to general practitioners were observed. Limitation: Physicians were hesitant to refrain from admission and diagnostic tests in patients classified as low risk by the HEART score. Conclusion: Using the HEART score during initial assessment of patients with chest pain is safe, but the effect on health care resources is limited, possibly due to nonadherence to management recommendations. Primary Funding Source: Netherlands Organisation for Health Research and Development.

Background: A myocardial bridge (MB) is a band of myocardium covering a coronary artery segment, typically located in the left anterior descending coronary artery (LAD). Bridged segments of the coronary artery are isolated from the influence of perivascular adipose tissue. The aims of this study were to investigate the relationship between MBs and atherosclerosis in bridged LAD segments and to evaluate whether perivascular adipose tissue is involved in this relationship. Methods: MBs were identified in the coronary arteries of patients referred for diagnostic cardiac CT. The calcium score of MBs of the LAD or, in patients without LAD-MBs, of a corresponding LAD segment at the same distance from its origin and over the same length was measured. Results: Of 128 patients, 56 (44%) had in total 73 MBs. The mean MB length was 22 ± 14 mm and the median MB thickness was 0.8 mm (interquartile range 0.3-2.1 mm). MBs in the LAD were present in 40 patients (31%). The calcium score was 0 in 95% of the LAD segments with MBs compared with 52% of the corresponding LAD segments without MBs. The association between LAD-MBs and calcium score (OR 0.06, 95% CI 0.01-0.25) was not influenced by age and gender, but was attenuated by local perivascular adipose tissue thickness (OR 0.35, 95% CI 0.04-2.70). Conclusions: Coronary artery segments covered with an MB have a lower calcium score than segments without an MB. The association between MBs and calcium scores was influenced by local perivascular adipose tissue thickness. © 2012 Elsevier Ireland Ltd.

Background Previous studies suggested that electrical abnormalities precede overt structural disease in arrhythmogenic right ventricular cardiomyopathy (ARVC). Abnormal RV deformation has been reported in early ARVC without structural abnormalities. The pathophysiological mechanisms underlying these abnormalities remain unknown. Objectives The authors used imaging and computer simulation to differentiate electrical from mechanical tissue substrates among ARVC clinical stages. Methods ARVC desmosomal mutation carriers (n = 84) were evaluated by electrocardiography (ECG), Holter monitoring, late-enhancement cardiac magnetic resonance imaging, and echocardiographic RV deformation imaging. Subjects were categorized based on the presence of 2010 International Task Force criteria: 1) subclinical stage (n = 21); 2) electrical stage (n = 15); and 3) structural stage (n = 48). Late enhancement was not present in any subclinical or electrical stage subjects. Results Three distinctive characteristic RV longitudinal deformation patterns were identified: type I: normal deformation (n = 12); type II: delayed onset of shortening, reduced systolic peak strain, and mild post-systolic shortening (n = 35); and type III: systolic stretching with large post-systolic shortening (n = 37). A majority (69%) of structural staged mutation carriers were type III, whereas a large proportion of both electrical and subclinical stage subjects (67% and 48%, respectively) were type II. Computer simulations demonstrated that the type II pattern can be explained by a combination of reduced contractility and mildly increased passive myocardial stiffness. This evolved into type III by aggravating both mechanical substrates. Electrical activation delay alone explained none of the patterns. Conclusions Different ARVC stages were characterized by distinct RV deformation patterns, all of which could be reproduced by simulating different degrees of mechanical substrates. Subclinical and electrical staged ARVC subjects already showed signs of local mechanical abnormalities. Our novel approach could lead to earlier disease detection and, thereby, influence current definitions of electrical and subclinical ARVC stages.

Background: Coronary artery disease affects both men and women. In this study, we examine sex-specific differences in occurrence of major adverse cardiovascular events (MACEs) after coronary angiography. Methods: We analyzed data from the coronary angiography cohort Utrecht Coronary Biobank (n = 1283 men, 480 women). Using Kaplan-Meier and multivariable Cox-regression, we tested for sex differences in MACE occurrence. Additionally, we compared mortality with an age- and sex-matched control group from the general Dutch population. Results: During a median follow-up of 2.1 years (interquartile range 1.6-2.8), MACEs occurred in 265 men and 103 women (20.7% vs 21.3%, P = .744). Women with myocardial infarction (MI) had significantly more MACE during follow-up than men (hazard ratio [HR] 1.66 for female sex, 95% confidence interval [CI] 1.10-2.50, P = .015), which was also the case for women who had multivessel disease (HR 1.41, 95% CI 1.03-1.94, P = .031). During follow-up, mortality in women presenting with MI was higher than mortality of women in the general population; men with MI did not show this disadvantage. Conclusion: MACEs occurred more often in women than in men who presented with MI or who had angiographic multivessel disease upon coronary angiography. Clinical trial registration: Clinicaltrials.gov identifier: NCT02304744. URL: https://clinicaltrials.gov/ct2/show/NCT02304744 .

Undetected heart failure appears to be an important health problem in patients with type 2 diabetes and aged ≥ 60 years. The prevalence of previously unknown heart failure in these patients is high, steeply rises with age, and is overall higher in women than in men. The majority of the patients with newly detected heart failure have a preserved ejection fraction. A diagnostic algorithm to detect or exclude heart failure in these patients with variables from the medical files combined with items from history taking and physical examination provides a good to excellent accuracy. Annual screening appears to be cost-effective. Both unrecognised heart failure with reduced and with preserved ejection fraction were associated with a clinically relevant lower health status in patients with type 2 diabetes. Also the prognosis of these patients was worse than of those without heart failure. Existing disease-management programs for type 2 diabetes pay insufficient attention to early detection of cardiovascular diseases, including heart failure. We conclude that more attention is needed for detection of heart failure in older patients with type 2 diabetes.

Background: Heart failure (HF), especially with preserved ejection fraction (HFpEF) is common in older patients with type 2 diabetes (T2DM), but often not recognized. Early HF detection in older T2DM patients may be worthwhile because treatment may be initiated in an early stage, with clear beneficial treatment in those with reduced ejection fraction (HFrEF), but without clear prognostic beneficial treatment in those with HFpEF. Because both types of HF may be uncovered in older T2DM, screening may improve health outcomes at acceptable costs. We assessed the cost-effectiveness of five screening strategies in patients with T2DM aged 60years or over. Methods: We built a Markov model with a lifetime horizon based on the prognostic results from our screening study of 581 patients with T2DM, extended with evidence from literature. Cost-effectiveness was calculated from a Dutch healthcare perspective as additional costs (Euros) per additional quality-adjusted life-year (QALY) gained. We performed probabilistic sensitivity analysis to assess robustness of these outcomes. Scenario analyses were performed to assess the influence of the availability of effective treatment of heart failure with preserved ejection fraction. Results: For willingness to pay values in the range of €6050/QALY-€31,000/QALY for men and €6300/QALY-€42,000/QALY for women, screening-based checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms had the highest probability of being cost-effective. For higher willingness-to-pay values, direct echocardiography was the preferred screening strategy. Cost-effectiveness of all screening strategies improved with the increase in effectiveness of treatment for HFpEF. Conclusions: Screening forHF in older community-dwelling patients with T2DM is cost-effective at the commonly used willingness-to-pay threshold of €20.000/QALY by checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms. The simplicity of such a strategy makes it feasible for implementation in existing primary care diabetes management programs.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetically determined myocardial disease predominantly affecting the right ventricle (RV). There is no single gold standard for the diagnosis of ARVC/D. New echocardiographic tools such as tissue deformation imaging allow quantitative regional wall motion analyses. This is especially important for early ARVC/D diagnosis where global RV dysfunction may be lacking. Several studies have shown incremental diagnostic value for tissue deformation imaging derived parameters in comparison to conventional echocardiography. 3D RV echocardiography is a new method to evaluate the RV and provides volumetric measurements in a broad spectrum of ARVC/D patients. Due to the frequent implantation of implantable cardioverter devices, echocardiography could play an important role in the follow-up of ARVC/D patients. Emerging new echocardiographic tools are currently changing the role of echocardiography in ARVC/D. In the future, MRI and echocardiography should be considered complementary to evaluate ARVC/D.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with desmosomal mutations. Although desmosomal disruption affects both ventricles and atria, little is known about atrial involvement in ARVD/C.To describe the extent and clinical significance of structural atrial involvement and atrial arrhythmias (AA) in ARVD/C stratified by genotype.We included 71 patients who met ARVD/C Task Force Criteria and underwent cardiac magnetic resonance (CMR) imaging and molecular genetic analysis. Indexed atrial end-diastolic volume and area-length-ejection-fraction (ALEF) were evaluated on CMR and compared to controls with idiopathic right ventricular outflow tract tachycardia (n = 40). The primary outcome was occurrence of AA (atrial fibrillation or atrial flutter) during follow-up, recorded by 12-lead ECG, Holter monitoring or implantable cardioverter defibrillator (ICD) interrogation.Patients harbored a desmosomal plakophilin-2 (PKP2) (n = 37) or nondesmosomal phospholamban (PLN) (n = 14) mutation. In 20 subjects, no pathogenic mutation was identified. Compared to controls, right atrial (RA) volumes were reduced in PKP2 (P = 0.002) and comparable in PLN (P = 0.441) mutation carriers. In patients with no mutation identified, RA (P = 0.011) and left atrial (P = 0.034) volumes were increased. Bi-atrial ALEF showed no significant difference between the groups. AA were experienced by 27% of patients and occurred equally among PKP2 (30%) and no mutation identified patients (30%), but less among PLN mutation carriers (14%).Genotype influences atrial volume and occurrence of AA in ARVD/C. While the incidence of AA is similar in PKP2 mutation carriers and patients with no mutation identified, PKP2 mutation carriers have significantly smaller atria. This suggests a different arrhythmogenic mechanism.

Differences in prognosis between women and men with atherosclerosis are currently under attention. Previous studies describe contradictory results and are restricted to one cardiovascular bed, while atherosclerosis is a systemic disease. We therefore studied the prognosis of women versus men in the SMART study, a large cohort of patients with clinically manifest atherosclerosis with extensive baseline and follow-up information.5349 patients (1347 women, 4002 men) with at least one type of atherosclerotic vascular disease (coronary artery disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm) were included in the SMART study, an ongoing long-term follow-up study. They all received a standardized cardiovascular work-up with a personalized therapy advice. All future cardiovascular events were collected prospectively. All-cause mortality, cardiovascular mortality and cardiovascular outcome (composite of myocardial infarction, stroke and cardiovascular death) were evaluated using Cox regression and expressed as hazard ratios (HR) with 95% confidence intervals (95%CI). Men served as the reference category. Different models were used to adjust for differences in baseline characteristics.Women and men had a mean age of 60 years and their median follow-up (range) was five years (13.5). The hazard ratios of all-cause mortality, cardiovascular death and cardiovascular outcome were 0.62 (95%CI: 0.51-0.75), 0.59 (95%CI: 0.46-0.75) and 0.73 (95%CI: 0.60-0.87). Neither differences in risk-factor profile nor the different vascular beds involved could explain this advantage.Women with cardiovascular disease who received a similar standardized cardiovascular work-up and personalized therapy advice as men had a favourable long-term outcome.

The overt stage of arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) is preceded by a concealed stage with minor or no signs of disease. However, sudden death may occur in this early phase. Deformation imaging may contribute to early diagnosis. The aims of this study were to compare the diagnostic accuracy of the conventional (1994) versus the recently published (2010) new echocardiographic criteria for ARVD/C and to evaluate the additional value of echocardiographic tissue deformation imaging to detect subclinical RV functional abnormalities in asymptomatic carriers of pathogenic ARVD/C mutations.Fourteen asymptomatic first-degree relatives of ARVD/C probands (the ARVD/C-r group; mean age, 38.0 ± 13.2 years) with a pathogenic plakophilin-2 mutation and a group of age-matched controls (n = 56; mean age, 38.2 ± 12.7 years) were included at a 1:4 ratio. A complete echocardiographic evaluation (dimensions, global systolic parameters, and visual assessment and deformation imaging of the RV free wall including Doppler tissue imaging and two-dimensional strain echocardiography) was obtained. Peak systolic strain less negative than -18% and/or postsystolic shortening (postsystolic index15%) in any RV segment was considered abnormal.RV dimensions in the ARVD/C-r group were similar to those in controls (RV outflow tract, 15.4 ± 2.9 vs 14.4 ± 1.9 mm/m(2), P = NS; RV inflow tract, 18.6 ± 2.6 vs 19.1 ± 2.6 mm/m(2), P = NS), and global systolic parameters were moderately reduced (tricuspid annular plane systolic excursion, 20.0 ± 3.2 vs 23.9 ± 2.8 mm, P = .001; RV fractional area change, 40.3 ± 8.4 vs 40.6 ± 7.1, P = NS). According to task force criteria, 57% of the ARVD/C-r group and 29% of controls were classified as abnormal when applying the 1994 criteria and 29% and 4% when applying the 2010 criteria, respectively. Doppler tissue imaging and two-dimensional strain deformation (and strain rate) values were reduced in the ARVD/C-r group in the basal and mid RV segments compared with controls (P.001). In the ARVD/C-r group, peak systolic strain less negative than -18% was seen in six patients (43%), postsystolic strain in nine (64%), and either abnormality in 10 (71%), almost exclusively in the basal segment; these findings were observed in none of the controls.The 2010 criteria for ARVD/C improve specificity, whereas sensitivity is significantly reduced in this asymptomatic population. In contrast, echocardiographic deformation imaging detects functional abnormalities in the subtricuspid region in 71% of asymptomatic carriers of a pathogenic plakophilin-2 mutation, while regional deformation was normal in all control subjects, indicating superiority of both sensitivity and specificity with these new modalities.

Background— The power of echocardiographic dyssynchrony indices to predict response to cardiac resynchronization therapy (CRT) appears to vary between indices and between studies. We investigated whether the variability of predictive power between the dyssynchrony indices can be explained by differences in their operational definitions. Methods and Results— In 132 CRT-candidates (left ventricular [LV] ejection fraction, 19 ± 6%; QRS width, 170 ± 22 ms), 4 mechanical dyssynchrony indices (septal systolic rebound stretch [SRSsept], interventricular mechanical dyssynchrony [IVMD], septal-to-lateral peak shortening delay [Strain-SL], and septal-to-posterior wall motion delay [SPWMD]) were quantified at baseline. CRT response was quantified as 6-month percent change of LV end-systolic volume. Multiscale computer simulations of cardiac mechanics and hemodynamics were used to assess the relationships between dyssynchrony indices and CRT response within wide ranges of dyssynchrony of LV activation and reduced contractility. In patients, SRSsept showed best correlation with CRT response followed by IVMD, Strain-SL, and SPWMD ( R =−0.56, −0.50, −0.48, and −0.39, respectively; all P Conclusions— The power to predict CRT response differs between indices of mechanical dyssynchrony. SRSsept and IVMD better represent LV dyssynchrony amenable to CRT and better predict CRT response than the indices assessing time-to-peak deformation or motion.

Influence of Preactivation on the ECG in CRT. Introduction: The aims of this study were to compare ECG signs of biventricular electrical resynchronization during cardiac resynchronization therapy (CRT) with various interventricular (VV) delays and to correlate these and other ECG characteristics with the acute hemodynamic benefit of CRT. Methods and Results: Thirty-four patients with heart failure and a left bundle branch block (LBBB) pattern were prospectively enrolled. A 12-lead surface ECG and the relative improvement in left ventricular (LV) dP/dtmax (the maximum rate of pressure rise) were recorded at baseline and during CRT with VV delays varying from 80 ms LV preactivation to 40 ms right ventricular (RV) preactivation. Rightward QRS-axis shift occurred in 71–80% among all VV delays. Activation reversal to dominant negative in leads I/aVL was progressively observed at increasing LV preactivation (53–65%) and less (18–22%) during RV preactivation. Activation reversal to dominant positive in leads V1/V2 was observed in 21–27% during LV preactivation and in 6–15% during RV preactivation. Higher acute response to CRT was independently predicted by a complete LBBB at baseline (regression coefficient B = 7.7 [0.3–15.0], P = 0.042), later timing of LV depolarization within the QRS at baseline (Q-LVsense: B = 0.2 [0.1–0.3], P = 0.002), and biventricular electrical resynchronization during CRT as evidenced by activation reversal in leads I/aVL (B = 9.9 [3.2–16.6], P = 0.005). Conclusion: ECG signs of biventricular electrical resynchronization are present over a wide range of LV preactivated VV delays but to a lesser extent during RV preactivation. The presence of complete LBBB and longer Q-LVsense at baseline and signs of biventricular electrical resynchronization during CRT predict higher acute hemodynamic response. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1237–1245, November 2012)

Cardiac regenerative therapy is still not used in daily clinical practice. A reason for this might be the modest effect on relevant global clinical endpoints [i.e. ejection fraction (EF)] in preclinical studies. To introduce proper improvement strategies, it is important to extend the focus from clinical endpoints to more detailed local measures of cardiac function. In this review, we discuss the measurement principles of all invasive and non-invasive techniques that are used to assess the local effects of cardiac regenerative therapy in order to improve feedback to researchers unravelling the dominant pathways that lead to effective cardiac regeneration. Generally adopted mechanisms of cardiac regenerative therapy are: (i) vasculogenesis, (ii) cardiomyogenesis, and (iii) matrix-assisted myocardium stabilization. Since direct in vivo measures of these mechanisms do not exist, we discuss the measurement techniques of local microvascular resistance, myocardial perfusion, viability, fibrosis, and deformation imaging. The ability of these techniques to reflect the mechanism of cardiac regenerative therapy, and the results of applications in stem cell studies are discussed, and critically commented upon. Special attention is given to applications of deformation imaging, since this has recently been suggested and used as a potential new technique to assess local changes of cardiac biomechanics, which requires special knowledge about cardiac physiology. We conclude that besides the clinically relevant EF measurements, detailed measures of local cardiac function provide information about the local changes induced by cardiac regenerative therapy. In particular, combination of deformation imaging, by ultrasound or magnetic resonance imaging, with simultaneously measured local geometry and pressure measurements is a promising approach to assess the effects of cardiac regenerative therapy on local cardiac biomechanics. This approach provides information about local tissue contractility, stiffness, and thereby remodelling. We recommend that researchers use this comprehensive approach in future studies.

Septal rebound stretch (SRSsept) is a distinctive characteristic of discoordination-related mechanical inefficiency. We assessed how intermediate- and long-term outcome after cardiac resynchronization therapy (CRT) relate to baseline SRSsept.A total of 101 patients (age 65 ± 11 years, 69 men, 18 New York Heart Association (NYHA) class IV, QRS 173 ± 23 ms) scheduled for CRT underwent clinical assessment, echocardiography, and brain-type natriuretic peptide (BNP) measurements before and 6.4 ± 2.3 months after CRT. Baseline SRSsept (all systolic stretch after initial shortening in the septum) was quantified by speckle tracking echocardiography. Primary composite end point was death, urgent cardiac transplantation, or left ventricular assist device implantation at the end of the study. Secondary end points were intermediate-term (6 months) response, quantified as decreases in left ventricular end-systolic volume (ΔLVESV) and BNP (ΔBNP). After a mean clinical follow-up of 15.6 ± 9.0 months; 23 patients had reached the primary end point. Baseline SRSsept (hazard ratio [HR] 0.742; 95% confidence intervals [CI] 0.601-0.916, P.01]) was independently associated with a better outcome and NYHA class (HR 5.786: 95% CI 2.341-14.299, P.001) with a worse outcome. Contrary to baseline NYHA class, baseline SRSsept was an independent predictor of both ΔLVESV (beta 0.53; P.001) and ΔBNP (beta 0.29; P.01). Intermediate-term ΔLVESV and ΔBNP were associated with a favorable long-term outcome.SRSsept at baseline is a strong, independent predictor of long-term prognosis after CRT and of improvements in left ventricular remodeling and neurohormonal activation at intermediate term.

Physiological cardiac adaptation in athletes is influenced by body surface area, gender, age, training intensity and sport type. This study assesses the influence of sport category and provides a physiological reference for sport category and gender.Three hundred and eighty-one subjects (mean age 25±5 years, range 18 to 39 years; 61% men) underwent cardiac MRI and ECG: 114 healthy non-athletes (≤3 training h/week) and 267 healthy elite athletes (mean 17±6.6 training h/week). Athletes performed low-dynamic high-static (LD-HS, n=42), high-dynamic low-static (HD-LS, n=144) or high-dynamic high-static sports (HD-HS, n=81).Left ventricular (LV) end-diastolic volume (EDV) index (ml/m(2)) for non-athletes/LD-HS/HD-LS/HD-HS, respectively, was 101/107/122/129 in men and 90/103/106/111 in women. LV end-diastolic mass (EDM) index (g/m(2)) for non-athletes/LD-HS/HD-LS/HD-HS was, respectively, 47/49/57/69 for men and 34/38/42/51 for women. Left or right ventricular EDV ratios were alike in all groups. LV EDV/EDM ratios were similar in non-athletes/LD-HS/HD-LS athletes, and only lower in HD-HS athletes, disproving selective ventricular wall thickening in LD-HS athletes. Multivariate linear regression demonstrated HD-LS and HD-HS sport category coefficients (p0.01) larger than those of training hours, gender and age (LV EDV/EDM coefficients for sport category LD-HS 6/0.75, HD-LS 16/7, HD-HS 21/17). ECG abnormalities were most frequent in HD-HS athletes and in male subjects.This study demonstrates a balanced cardiac adaptation with preserved ratios of LV/right ventricular volume (in all sport categories) and LV volume/wall mass (in LD-HS and HD-LS sports). Sport category has a strong impact on cardiac adaptation. HD-HS sports show the largest changes, whereas LD-HS sports show dimensions similar to non-athletes.

The combination of chronic kidney disease (CKD) and heart failure (HF) is associated with an adverse prognosis. Although clinical studies hint at a specific bidirectional interaction between HF and CKD, insight into the pathogenesis of cardiorenal syndrome (CRS) remains limited. We review available evidence on cardiorenal interactions from animal models of CKD and HF and discuss several studies that employed a “double-hit” model to research organ cross talk between the heart and kidneys. Regarding cardiac changes in CKD models, parameters of cardiac remodeling are equivocal and cardiac systolic function generally remains preserved. Structural changes include hypertrophy, fibrosis, and microvasculopathy. In models of HF, data on renal pathology are mostly limited to functional hemodynamic changes. Most double-hit models were unable to show that combined renal and cardiac injury induces additive damage to both organs, perhaps because of the short study duration or absence of organ failure. Because of this lack of “dual-failure” models, we have developed two rat models of combined CKD and HF in which renal dysfunction induced by a subtotal nephrectomy preceded cardiac dysfunction. Cardiac dysfunction was induced either functionally by nitric oxide depletion or structurally by myocardial infarction. In both models, we found that cardiac remodeling and failure were worse in CKD rats compared with controls undergoing the same cardiac insult. Variables of renal damage, like glomerulosclerosis and proteinuria, were also further worsened by combined cardiorenal injury. These studies show that target organ cross talk does occur in CRS. These models may be useful for interventional studies in rats.

Coexistence of chronic kidney disease (CKD) and heart failure (HF) in humans is associated with poor outcome. We hypothesized that preexistent CKD worsens cardiac outcome after myocardial infarction, and conversely that ensuing HF worsens progression of CKD. Subtotally nephrectomized (SNX) or sham-operated (CON) rats were subjected to coronary ligation (CL) or sham surgery in week 9 to realize four groups: CON, SNX, CON + CL, and SNX + CL. Blood pressure and renal function were measured in weeks 8, 11, 13, and 15. In week 16, cardiac hemodynamics and end-organ damage were assessed. Blood pressure was significantly lower in SNX + CL vs. SNX. Despite this, glomerulosclerosis was more severe in SNX + CL vs. SNX. Two weeks after CL, SNX + CL had more cardiac dilatation compared with CON + CL (end-diastolic volume index: 0.28 ± 0.04 vs. 0.19 ± 0.03 ml/100 g body wt; mean ± SD, P < 0.001), although infarct size was similar. During follow-up in SNX + CL, ejection fraction declined. Mortality was only observed in SNX + CL (2 out of 9). In SNX + CL, end-diastolic pressure (18 ± 4 mmHg) and tau (29 ± 9 ms), the time constant of active relaxation, were significantly higher compared with SNX (13 ± 3 mmHg, 20 ± 4 ms; P < 0.01) and CON + CL (11 ± 5 mmHg, 17 ± 2 ms; P < 0.01). The diameter of small arterioles in the myocardium was significantly decreased in SNX + CL vs. CON + CL ( P < 0.01). Urinary excretion of NO metabolites was significantly lower in SNX + CL compared with both CL and SNX. This study demonstrates the existence of more heart and more kidney damage in a new model of combined CKD and HF than in the individual models. Such enhanced damage appears to be separate from systemic hemodynamic changes. Reduced nitric oxide availability may have played a role in both worsened glomerulosclerosis and cardiac diastolic function and appears to be a connector in the cardiorenal syndrome.

Background— Early diagnosis of nonacute heart failure is crucial because prompt initiation of evidence-based treatment can prevent or slow down further progression. To diagnose new-onset heart failure in primary care is challenging. Methods and Results— This is a cross-sectional diagnostic accuracy study with external validation. Seven hundred twenty-one consecutive patients suspected of new-onset heart failure underwent standardized diagnostic work-up including chest x-ray, spirometry, ECG, N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement, and echocardiography in specially equipped outpatient diagnostic heart failure clinics. The presence of heart failure was determined by an outcome panel using the initial clinical data and 6-month follow-up data, blinded to biomarker data. Of the 721 patients, 207 (28.7%) had heart failure. The combination of 3 items from history (age, coronary artery disease, and loop diuretic use) plus 6 from physical examination (pulse rate and regularity, displaced apex beat, rales, heart murmur, and increased jugular vein pressure) showed independent diagnostic value (c-statistic 0.83). NT-proBNP was the most powerful supplementary diagnostic test, increasing the c-statistic to 0.86 and resulting in net reclassification improvement of 69% ( P Conclusions— In this study, we estimated the quantitative diagnostic contribution of elements of the history and physical examination in the diagnosis of heart failure in primary care outpatients, which may help to improve clinical decision making. The largest additional quantitative diagnostic contribution to those elements was provided by measurement of NT-proBNP. For daily practice, a diagnostic rule was derived that may be useful to quantify the probability of heart failure in patients with new symptoms suggestive of heart failure.