Addition of FFRct in the diagnostic pathway of patients with stable chest pain to reduce unnecessary invasive coronary angiography (FUSION) : Rationale and design for the multicentre, randomised, controlled FUSION trial.

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used in the diagnostic work-up of patients with stable chest pain. CCTA has an excellent negative predictive value, but a moderate positive predictive value for detecting coronary stenosis. Computed tomography-derived fractional flow reserve (FFRct) is a non-invasive, well-validated technique that provides functional assessment of coronary stenosis, improving the positive predictive value of CCTA. However, to determine the value of FFRct in routine clinical practice, a pragmatic randomised, controlled trial (RCT) is required. We will conduct an RCT to investigate the impact of adding FFRct analysis in the diagnostic pathway of patients with a coronary stenosis on CCTA on the rate of unnecessary invasive coronary angiography, cost-effectiveness, quality of life and clinical outcome. METHODS: The FUSION trial is a prospective, multicentre RCT that will randomise 528 patients with stable chest pain and anatomical stenosis of ≥ 50% but < 90% in at least one coronary artery of ≥ 2 mm on CCTA, to FFRct-guided care or usual care in a 1:1 ratio. Follow-up will be 1 year. The primary endpoint is the rate of unnecessary invasive coronary angiography within 90 days. CONCLUSION: The FUSION trial will evaluate the use of FFRct in stable chest pain patients from the Dutch perspective. The trial is funded by the Dutch National Health Care Institute as part of the research programme 'Potentially Promising Care' and the results will be used to assess if FFRct reimbursement should be included in the standard health care package.

Feasibility and potential benefit of pre-procedural CMR imaging in patients with ischaemic cardiomyopathy undergoing cardiac resynchronisation therapy.

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.

Survival analysis of patients with rheumatic MS after PBMV compared with MVS in a low-to-middle-income country.

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.

Assessment of LV ejection fraction using real-time 3D echocardiography in daily practice: direct comparison of the volumetric and speckle tracking methodologies to CMR.

AIMS: This study is the first to directly compare two widely used real-time 3D echocardiography (RT3DE) methods of cardiac magnetic resonance imaging (CMR) and assess their reproducibility in experienced and less experienced observers. METHODS: Consecutive patients planned for CMR underwent RT3DE within 8 h of CMR with Philips (volumetric method) and Toshiba Artida (speckle tracking method). Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were measured using RT3DE, by four trained observers, and compared with CMR values. RESULTS: Thirty-five patients were included (49.7 ± 15.7 years; 55 % male), 30 (85.7 %) volumetric and 27 (77.1 %) speckle tracking datasets could be analysed. CMR derived LVEDV, LVESV and LVEF were 198 ± 58 ml, 106 ± 53 ml and 49 ± 15 %, respectively. LVEF derived from speckle tracking was accurate and reproducible in all observers (all intra-class correlation coefficients (ICC) > 0.86). LVEF derived from the volumetric method correlated well to CMR in experienced observers (ICC 0.85 and 0.86) but only moderately in less experienced observers (ICC 0.58 and 0.77) and was less reproducible in these observers (ICC = 0.55). Volumes were significantly underestimated compared with CMR (p < 0.001). CONCLUSION: This study demonstrates that both RT3DE methodologies are sufficiently accurate and reproducible for use in daily practice. However, experience importantly influences the accuracy and reproducibility of the volumetric method, which should be considered when introducing this technique into clinical practice.

High prevalence of previously unknown heart failure and left ventricular dysfunction in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to assess the prevalence of (unknown) heart failure and left ventricular dysfunction in older patients with type 2 diabetes. METHODS: In total, 605 patients aged 60 years or over with type 2 diabetes in the south west of the Netherlands participated in this cross-sectional study (response rate 48.7%), including 24 with a cardiologist-confirmed diagnosis of heart failure. Between February 2009 and March 2010, the patients without known heart failure underwent a standardised diagnostic work-up, including medical history, physical examination, ECG and echocardiography. An expert panel used the criteria of the European Society of Cardiology to diagnose heart failure. RESULTS: Of the 581 patients studied, 161 (27.7%; 95% CI 24.1%, 31.4%) were found to have previously unknown heart failure: 28 (4.8%; 95% CI 3.1%, 6.6%) with reduced ejection fraction, and 133 (22.9%; 95% CI 19.5%, 26.3%) with preserved ejection fraction. The prevalence of heart failure increased steeply with age. Heart failure with preserved ejection fraction was more common in women. Left ventricular dysfunction was diagnosed in 150 patients (25.8%; 95% CI 22.3%, 29.4%); 146 (25.1%; 95% CI 21.6%, 28.7%) had diastolic dysfunction. CONCLUSIONS/INTERPRETATION: This is the first epidemiological study that provides exact prevalence estimates of (previously unknown) heart failure and left ventricular dysfunction in a representative sample of patients with type 2 diabetes. Previously unknown heart failure and left ventricular dysfunction are highly prevalent. Physicians should pay special attention to 'unmasking' these patients.

The time window of MRI of murine atherosclerotic plaques after administration of CB2 receptor targeted micelles: inter-scan variability and relation between plaque signal intensity increase and gadolinium content of inversion recovery prepared versus non-prepared fast spin echo.

Single fast spin echo scans covering limited time frames are mostly used for contrast-enhanced MRI of atherosclerotic plaque biomarkers. Knowledge on inter-scan variability of the normalized enhancement ratio of plaque (NER(plaque)) and relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo is limited. Study aims were: evaluation of (1) timing of MRI after intravenous injection of cannabinoid-2 receptor (CB2-R) (expressed by human and mouse plaque macrophages) targeted micelles; (2) inter-scan variability of inversion-recovery fast spin echo and fast spin echo; (3) relation between NER(plaque) and gadolinium content for inversion-recovery fast spin echo and fast spin echo. Inversion-recovery fast spin echo/fast spin echo imaging was performed before and every 15 min up to 48 h after injection of CB2-R targeted or control micelles using several groups of mice measured in an interleaved fashion. NER(plaque) (determined on inversion-recovery fast spin echo images) remained high (∼2) until 48 h after injection of CB2-R targeted micelles, whereas NER(plaque) decreased after 36 h in the control group. The inter-scan variability and relation between NER(plaque) and gadolinium (assessed with inductively coupled plasma- mass spectrometry) were compared between inversion-recovery fast spin echo and fast spin echo. Inter-scan variability was higher for inversion-recovery fast spin echo than for fast spin echo. Although gadolinium and NER(plaque) correlated well for both techniques, the NER of plaque was higher for inversion-recovery fast spin echo than for fast spin echo. In mice injected with CB2-R targeted micelles, NER(plaque) can be best evaluated at 36-48 h post-injection. Because NER(plaque) was higher for inversion-recovery fast spin echo than for fast spin echo, but with high inter-scan variability, repeated inversion-recovery fast spin echo imaging and averaging of the obtained NER(plaque) values is recommended.

Simultaneous aortic and coronary assessment in abdominal aortic aneurysm patients by thoraco-abdominal 64-detector-row CT angiography: estimate of the impact on preoperative management: a pilot study.

OBJECTIVES: To estimate the influence of information on the coronary arteries obtained from routine thoraco-abdominal CT angiography (CTA) on pre-operative clinical management in abdominal aortic aneurysm (AAA) patients. METHODS: Twenty-eight AAA patients underwent pre-operative thoraco-abdominal electrocardiography (ECG)-gated 64-detector-row CTA to evaluate aortic pulsatility for prosthesis size matching. Retrospectively, the coronaries were reconstructed from the same data set and scored on a per segment basis for stenosis (0%, 50%) and grading confidence (poor, adequate or high). An experienced cardiologist was presented information on patient characteristics obtained from patient records and CTA findings. Suggested changes in European Society of Cardiology guidelines based patient management based on CTA information were scored. RESULTS: On CTA, 17 patients (61%) had significant coronary disease (>50% stenosis) including left main (n=4), single (n=7) and multiple (n=6) vessel disease. Grading confidence was adequate or high in 86% of proximal and middle segments. Based on CTA findings, patient management would have been changed in 4 out of the 28 patients (14%; 95% CI 1-27%) by adding coronary angiography (n=4). In five patients who underwent coronary artery bypass grafting previously, CT did not change management but confirmed graft patency. CONCLUSIONS: Information on coronary pathology and coronary bypass graft patency can be readily obtained from thoraco-abdominal CTA and may alter pre-operative patient management, as shown in 14% of AAA patients in our study.

Left ventricular hypertrophy: a shift in paradigm.

Observational studies have identified left ventricular hypertrophy (LVH) as a strong, independent risk factor for the development of heart failure (HF), coronary heart disease and stroke. LVH develops in response to hemodynamic overload. Classical conceptualization has it that LVH would start as an adaptive, beneficial response in order to normalize wall stress. With progression of the disease, deterioration to maladaptive hypertrophy, and further on to HF could occur. Recent experiments in animal models of pressure-overload and myocardial infarction now challenge this concept by demonstrating that blunting the hypertrophic response is actually associated with preserved cardiac function, and with improved survival. These findings may have profound therapeutical implications.

Clinical implementation of guidelines for cardioverter defibrillator implantation: lost in translation?

PURPOSE: Guidelines for implantation of cardioverter defibrillators (ICD) are increasingly including indications for primary prevention of sudden cardiac death in high-risk groups, where ICDs were traditionally implanted for secondary prevention. We performed a single-centre audit to evaluate adherence to the recent Dutch guidelines. METHODS: All 1886 patients visiting a large regional Dutch teaching hospital (attending 1.8 to 2.0% of the Dutch population) in November 2005 were screened using the recently updated Dutch guidelines. Patients fulfilling these criteria were categorised as having an ICD indication for primary or secondary prevention. RESULTS: 135 patients had an indication for ICD, 19 of whom had one or received one. Of the remaining 116 patients, 14 were 'new' to the department of cardiology. The 102 'known' patients had 466 doctor-patient contacts in the previous year, which averages 4.57 cardiology contacts per patient per year. Patients were more likely to receive an ICD for the secondary prevention of SCD (10/11, 91%) than for primary prevention (9/124, 7%). CONCLUSION: In a large regional teaching hospital in the Netherlands, only a small proportion of patients eligible for ICD implantation actually receive one. Cardiologists tend to implant ICDs for secondary prevention of SCD. The low ICD implantation rate for primary prevention of SCD may relate to logistics (e.g. permission to implant ICDs, the presence of an electrophysiology lab) or the perceived low cost-benefit ratio. Our results indicate that once the substantial backlog (13,500 ICDs) has been addressed, the annual implantation of new ICDs should rise from the current 125 to at least 510 per million inhabitants per year in the Netherlands. (Neth Heart J 2007;15:129-32.).

Lessons from france: the cardiovascular prevention clinic in the la pitié-salpêtrière hospital in paris.

Cardiovascular disease is the principal cause of morbidity and mortality in the Netherlands. In this background, various initiatives have been launched to reduce the frequency of cardiovascular disease. One of those is the creation of clinical units with a special focus on prevention of cardiovascular disease. Hitherto, the prevention programmes of these clinics have been heterogeneous and therefore difficult to compare with respect to results. Similar developments in creating clinical initiatives concerning prevention of cardiovascular disease are found across Europe. With this in mind, lessons could be learned from each other's experiences. In our contribution, we would like to present the Cardiovascular Prevention Clinic in the Pitié- Salpêtrière Hospital in Paris, France, as an interesting example of a well-acknowledged cardiovascular prevention clinic that combines both daily clinical care and cardiovascular science. (Neth Heart J 2007;15:22-6.).

Arrhythmogenic right ventricular cardiomyopathy: asymptomatic to life threatening as illustrated by the cases of two sisters.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder of unknown cause that is characterised by fibrofatty replacement, primarily of the right ventricular myocardium, which can lead to life-threatening arrhythmias. It is a disease with a very diverse phenotype. In the present article we describe two sisters, each with a different manifestation of this disorder. The first patient died suddenly at the age of 18 during exercise. Her 17-year-old sister did not have any abnormalities at first cardiac consultation, but a few years later she met several diagnostic criteria for ARVC and an internal cardioverter defibrillator was implanted. Genetic analysis identified a mutation in the plakophilin- 2 (PKP2) gene. Cardiac evaluation of a third sister did not reveal any abnormalities and no mutation in the PKP2 gene was found. Thus, ARVC can vary in its clinical presentation, not only between siblings but also in time. This raises difficulties for the physician for diagnosis, treatment and followup. It is important for the physician involved to consider this disease in patients with palpitations and syncope, especially when there is a family history of ARVC or unexplained sudden death. (Neth Heart J 2007;15:348-53.).

Rationale and design of the SMART Heart study: A prediction model for left ventricular hypertrophy in hypertension.

Left ventricular hypertrophy (LVH) is an independent risk factor for the development of heart failure, coronary heart disease and stroke. LVH develops in response to haemodynamic overload, e.g. hypertension. LVH was originally thought to start as an adaptive and beneficial response required to normalise wall stress. However, this concept has been challenged by recent animal experiments suggesting that any degree of LVH is detrimental for the preservation of cardiac function and survival. If confirmed in humans, these findings imply that an increase in LV mass should be prevented, e.g. by lifestyle or pharmacological interventions. To facilitate and optimise interventions, the SMART Heart study was recently set up to develop a prediction model, also involving single nucleotide polymorphism data, for the identification of subjects at high risk of developing LVH in hypertension. For this purpose 1000 subjects with chronic hypertension will undergo cardiac MR imaging. In addition, this study allows the extrapolation of animal experimental genetic research into the human situation. (Neth Heart J 2007;15:295-8.).

WITHDRAWN: Giant Multiperforated Atrial Septal Aneurysm in a Patient with Paroxysmal Atrial Fibrillation.

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 154-156, . The duplicate article has therefore been withdrawn.

Delays in the treatment of patients with acute coronary syndrome: Focus on pre-hospital delays and non-ST-elevated myocardial infarction.

Delays in patients suspected of acute coronary syndrome (ACS) should be kept as short as possible to reduce complications and mortality. In this review we discuss the substantial pre-hospital delays of ST-elevated myocardial infarction (STEMI) patients as well as non-STEMI patients. The pre-hospital delays include patient, doctor and emergency medical transport (EMT) delay. Patient delay is among the longest in the pre-hospital chain of ACS patients. Interventions as mass media campaigns or individual education programs have not yet shown much improvement. Patients with chest pain most often contact the general practitioner (GP) instead of the recommended EMT, increasing delays as well. To decrease the delays by referring all patients promptly and without restriction to the emergency department (ED) is not feasible. Up to 80% of the patients with chest pain do not have a cardiac diagnosis and thus referral of all these patients would result in overcrowding of the ED. Triage is therefore crucial. Triage of patients with chest pain is therefore imperative and there is a great need of (validated) triage tools.

Long-term blood pressure monitoring and echocardiographic findings in patients with end-stage renal disease: reverse epidemiology explained?

BACKGROUND: In patients with end-stage renal disease (ESRD) hypertension is common and often leads to left ventricular (LV) hypertrophy and diastolic dysfunction, but hypotension at the onset of dialysis is associated with increased mortality. We studied blood pressure data over longer periods of time in patients on haemodialysis and related them to echocardiographic outcome, in order to elucidate these contradictory findings. METHODS: In 50 haemodialysis patients mean arterial pressure (MAP) and pulse pressure (PP) were calculated in the first three months of haemodialysis, the complete period from the start of haemodialysis until echocardiography and the last three months of haemodialysis before echocardiography. Hypertension load, pulse pressure and interdialytic weight gain were quantified and related to echocardiography. RESULTS: LV mass index was associated with MAP in all three periods, and also with the hypertension load, PP and PP load. In patients with LV dilatation, MAP and PP averaged over the complete period of dialysis were 5 to 7 mmHg higher than in patients without LV dilatation. Blood pressure parameters were the same in patients with or without LV diastolic dysfunction or systolic dysfunction. Systolic dysfunction was more frequent in patients undergoing long-term haemodialysis treatment. Interdialytic weight gain was not associated with any of the echocardiographic variables. CONCLUSION: When long-term blood pressure values are considered, hypertension is associated with parameters of early cardiac damage such as increased LV mass index and not with parameters of advanced heart failure such as systolic dysfunction. This supports the hypothesis that the presence of advanced heart failure reciprocally influences blood pressure in a negative way, thereby explaining the 'reverse epidemiology' of blood pressure and mortality in ESRD.

PR and OTc interval prolongation on the electrocardiogram after binge drinking in healthy individuals.

BACKGROUND: Acute, excessive alcohol intake has been associated with an increased cardiovascular mortality in otherwise healthy individuals. It predisposes to accelerated atherosclerosis resulting in acute coronary events but also arrhythmias have been described, such as atrial fibrillation and life-threatening re-entrant ventricular arrhythmias. QTc prolongation is associated with an increased risk of ventricular tachyarrhythmias and an independent risk factor for sudden cardiac death. The aim of the study is to investigate the effect of binge drinking on the conduction intervals in healthy individuals. METHODS: Ten of the volunteers drank red wine while the other ten volunteers drank a sweet designer drink. A follow-up of blood pressure, heart rate, ECG and laboratory findings was performed at an ethanol level of 0, 0.4 and 0.8%, respectively. RESULTS: Fifteen volunteers showed a prolongation of the PR interval, 13 of the QRS complex, 9 of the QT interval and 13 of the QTc interval. PR interval increased from 149 +/- 16 ms to 163 +/- 11 ms (p < 0.05). The heart rate-adjusted QT interval increased from 400 +/- 24 ms to 426 +/- 52 ms (p < 0.05). Heart rate and systolic blood pressure did not significantly change due to the ingestion. CONCLUSION: Acute ingestion of alcohol in a healthy population can induce prolongation of PR and QTc interval.

Progress in noninvasive coronary artery imaging using multislice CT.

Conventional coronary angiography (CAG) has been the reference standard for the assessment of coronary artery disease since its introduction in 1958. However, several studies have shown that diagnostic CAG has an average morbidity of 2% and a mortality of approximately 0.1%. In the last decade, progress in medical imaging has opened the way to noninvasive assessment of the coronary arteries at lower cost and risk. Of the different modalities, multislice CT (MSCT) has made the biggest step forward. At the 2005 European Congress of Radiology (ECR), experiences with the latest developments in noninvasive coronary artery imaging were reported. This report summarises the advances in the use of MSCT in coronary stenosis detection, emergency decision-making, plaque imaging, and the analysis of cardiac function and late enhancement. Also, attention is paid to new strategies to reduce MSCT-related radiation exposure.

Autologous Mesenchymal Stem Cells Show More Benefit on Systolic Function Compared to Bone Marrow Mononuclear Cells in a Porcine Model of Chronic Myocardial Infarction.

Cardiac cell therapy is a strategy to treat patients with chronic myocardial infarction (MI). No consensus exists regarding the optimal cell type. First, a comparison between autologous bone marrow-derived mononuclear cells (BMMNC) and mesenchymal stem cells (MSC) on therapeutic efficacy after MI was performed. Next, the effect of repetitive, NOGA-guided transendocardial injection was determined via a crossover design. Nineteen pigs were allocated in three groups: (1) placebo (at 4 and 8 weeks), (2) MSC (followed by placebo at 8 weeks), or (3) BMMNC (followed by MSC at 8 weeks) delivery including a priming strategy to enhance MSC effect. At 4 weeks, ejection fraction (EF) was significantly improved after MSC injection and not by BMMNC injection. After 8 weeks, no difference was observed in EF between cell-treated groups demonstrating the positive systolic effect of MSC. This study showed that MSC rather than BMMNC injection improves systolic function in chronic MI.