Smoking cessation and risk of recurrent cardiovascular events and mortality after a first manifestation of arterial disease.

AIMS: To quantify the relation between smoking cessation after a first cardiovascular (CV) event and risk of recurrent CV events and mortality. METHODS: Data were available from 4,673 patients aged 61 ± 8.7 years, with a recent (≤1 year) first manifestation of arterial disease participating in the SMART-cohort. Cox models were used to quantify the relation between smoking status and risk of recurrent major atherosclerotic cardiovascular events (MACE including stroke, MI and vascular mortality) and mortality. In addition, survival according to smoking status was plotted, taking competing risk of non-vascular mortality into account. RESULTS: A third of the smokers stopped after their first CV event. During a median of 7.4 (3.7-10.8) years of follow-up, 794 patients died and 692 MACE occurred. Compared to patients who continued to smoke, patients who quit had a lower risk of recurrent MACE (adjusted HR 0.66, 95% CI 0.49-0.88) and all-cause mortality (adjusted HR 0.63, 95% CI 0.48-0.82). Patients who reported smoking cessation on average lived 5 life years longer and recurrent MACE occurred 10 years later. In patients with a first CV event >70 years, cessation of smoking had improved survival which on average was comparable to former or never smokers. CONCLUSIONS: Irrespective of age at first CV event, cessation of smoking after a first CV event is related to a substantial lower risk of recurrent vascular events and all-cause mortality. Since smoking cessation is more effective in reducing CV risk than any pharmaceutical treatment of major risk factors, it should be a key objective for patients with vascular disease.

On-screen image-guided lead placement in cardiac resynchronization therapy: Feasibility and outcome in a multicenter setting.

Background: Image guidance to assist left ventricular (LV) lead placement may improve outcome after cardiac resynchronization therapy (CRT), but previous approaches and results varied greatly, and multicenter feasibility is lacking altogether. Objective: We sought to investigate the multicenter feasibility of image guidance for periprocedural assistance of LV lead placement for CRT. Methods: In 30 patients from 3 hospitals, cardiac magnetic resonance imaging was performed within 3 months prior to CRT to identify myocardial scar and late mechanical activation (LMA). LMA was determined using radial strain, plotted over time. Segments without scar but clear LMA were classified as optimal for LV lead placement, according to an accurate 36-segment model of the whole heart. LV leads were navigated using image overlay with periprocedural fluoroscopy. After 6 months, volumetric response and super-response were defined as ≥15% or ≥30% reduction in LV end-systolic volume, respectively. Results: Periprocedural image guidance was successfully performed in all CRT patients (age 66 ± 10 years; 59% men, 62% with nonischemic cardiomyopathy, 69% with left bundle branch block). LV leads were placed as follows: within (14%), adjacent (62%), or remote (24%) from the predefined target. According to the conventional 18-segment model, a remote position occurred only once (3%). On average, 86% of patients demonstrated a volumetric response (mean LV end-systolic volume reduction 36 ± 29%), and 66% of all patients were super-responders. Conclusion: On-screen image guidance for LV lead placement in CRT was feasible in a multicenter setting. Efficacy will be further investigated in the randomized controlled ADVISE (Advanced Image Supported Lead Placement in Cardiac Resynchronization Therapy) trial (NCT05053568).

Transendocardial cell injection is not superior to intracoronary infusion in a porcine model of ischaemic cardiomyopathy: a study on delivery efficiency.

Stem cell therapy is a new strategy for chronic ischaemic heart disease in patients. However, no consensus exists on the most optimal delivery strategy. This randomized study was designed to assess cell delivery efficiency of three clinically relevant strategies: intracoronary (IC) and transendocardial (TE) using electromechanical mapping guidance (NOGA) compared to surgical delivery in a chronic pig model of ischaemic cardiomyopathy. Twenty-four animals underwent delivery of 10(7) autologous Indium-oxine-labelled bone marrow-derived mesenchymal stem cells (MSC) 4 weeks after infarction and were randomized to one of three groups (n = 8 each group): IC, TE or surgical delivery (reference group). Primary endpoint was defined as percentage (%) of injected dose per organ and assessed by in vivo gamma-emission counting. In addition, troponin and coronary flow were assessed before and after MSC injection. Blinded endpoint analysis showed no significant difference in efficiency after surgical (16 ± 4%), IC (11 ± 1%) and TE (11 ± 3%) (P = 0.52) injections. IC showed less variability in efficiency compared with TE and surgical injection. Overall, TE injection showed less distribution of MSC to visceral organs compared with other modalities. Troponin rise and IC flow did not differ between the percutaneous groups. This randomized study showed no significant difference in cell delivery efficiency to the myocardium in a clinically relevant ischaemic large animal model between IC and TE delivery. In addition, no differences in safety profile were observed. These results are important in view of the choice of percutaneous cell delivery modality in future clinical stem cell trials.

Inducible cardiac ischaemia is related to a decrease in the whole-blood Toll-like receptor 2 and 4 response.

TLR (Toll-like receptor) activation-induced inflammatory responses are important in the progression of atherosclerosis. We previously showed that TLR-dependent leucocyte responsiveness is acutely attenuated following percutaneous coronary intervention or vascular surgery. Furthermore, cytokine release following whole-blood TLR-2 and TLR-4 stimulation is negatively correlated with fractional flow reserve, suggesting that chronic ischaemia can elicit an enhanced inflammatory response. In the present study, we assessed the association between leucocyte TLR-2 and TLR-4 responsiveness and pre-existent and inducible ischaemia in patients undergoing SPECT (single-photon emission computed tomography)-MPI (myocardial perfusion imaging). TLR-2, TLR-4 and CD11b expression on monocytes were measured in blood samples that were obtained from 100 patients with suspected coronary artery disease before and after myocardial stress testing for SPECT-MPI. IL-8 (interleukin-8) levels were determined after whole-blood stimulation with Pam3Cys (TLR-2) and LPS (lipopolysaccharide; TLR-4). On the basis of SPECT-MPI, patients were categorized into three groups: reversible defect, irreversible defect and no defect. Myocardial stress induced a reduction in TLR-4 expression (2.46±0.21 compared with 2.17±0.16 arbitrary units, P=0.001) and CD11b expression (83.2±1.73 compared with 76.0±1.89 arbitrary units, P<0.001). TLR-induced IL-8 production before myocardial stress induction was not associated with the results of SPECT-MPI. However, a significant decrease in IL-8 production following TLR stimulation was observed after stress, which was more pronounced in patients with a reversible defect. In conclusion, inducible ischaemia is associated with a decrease in whole-blood TLR-2 and TLR-4 response. These results point to a regulating role of TLRs in order to prevent excessive inflammatory events known to occur during acute ischaemia.

A head-to-head comparison of speckle tracking echocardiography and feature tracking cardiovascular magnetic resonance imaging in right ventricular deformation.

AIMS: Speckle tracking echocardiography (STE) and feature tracking cardiovascular magnetic resonance imaging (FT-CMR) are advanced imaging techniques which are both used for quantification of global and regional myocardial strain. Direct comparisons of STE and FT-CMR regarding right ventricular (RV) strain analysis are limited. We aimed to study clinical performance, correlation and agreement of RV strain by these techniques, using arrhythmogenic right ventricular cardiomyopathy (ARVC) as a model for RV disease. METHODS AND RESULTS: We enrolled 110 subjects, including 34 patients with definite ARVC, 30 preclinical relatives of ARVC patients, and 46 healthy control subjects. Global and regional RV longitudinal peak strain (PS) were measured by STE and FT-CMR. Both modalities showed reduced strain values in ARVC patients compared to ARVC relatives (STE global PS: P < 0.001; FT-CMR global PS: P < 0.001) and reduced strain values in ARVC relatives compared to healthy control subjects (STE global PS: P = 0.042; FT-CMR global PS: P = 0.084). There was a moderate, albeit significant correlation between RV strain values obtained by STE and FT-CMR [global PS r = 0.578 (95% confidence interval 0.427-0.697), P < 0.001]. Agreement between the techniques was weak (limits of agreement for global PS: ±11.8%). Correlation and agreement both deteriorated when regional strain was studied. CONCLUSION: RV STE and FT-CMR show a similar trend within the spectrum of ARVC and have significant correlation, but inter-modality agreement is weak. STE and FT-CMR may therefore both individually have added value for assessment of RV function, but RV PS values obtained by these techniques currently cannot be used interchangeably in clinical practice.

The nitric oxide donor molsidomine rescues cardiac function in rats with chronic kidney disease and cardiac dysfunction.

We recently developed a rat model of cardiorenal failure that is characterized by severe left ventricular systolic dysfunction (LVSD) and low nitric oxide (NO) production that persisted after temporary low-dose NO synthase inhibition. We hypothesized that LVSD was due to continued low NO availability and might be reversed by supplementing NO. Rats underwent a subtotal nephrectomy and were treated with low-dose NO synthase inhibition with N(ω)-nitro-l-arginine up to week 8. After 3 wk of washout, rats were treated orally with either the long-acting, tolerance-free NO donor molsidomine (Mols) or vehicle (Veh). Cardiac and renal function were measured on weeks 11, 13, and 15. On week 16, LV hemodynamics and pressure-volume relationships were measured invasively, and rats were killed to quantify histological damage. On week 15, blood pressure was mildly reduced and creatinine clearance was increased by Mols (both P < 0.05). Mols treatment improved ejection fraction (53 ± 3% vs. 37 ± 2% in Veh-treated rats, P < 0.001) and stroke volume (324 ± 33 vs. 255 ± 15 µl in Veh-treated rats, P < 0.05). Rats with Mols treatment had lower end-diastolic pressures (8.5 ± 1.1 mmHg) than Veh-treated rats (16.3 ± 3.5 mmHg, P < 0.05) and reduced time constants of relaxation (21.9 ± 1.8 vs. 30.9 ± 3.3 ms, respectively, P < 0.05). The LV end-systolic pressure-volume relationship was shifted to the left in Mols compared with Veh treatment. In summary, in a model of cardiorenal failure with low NO availability, supplementing NO significantly improves cardiac systolic and diastolic function without a major effect on afterload.

Erythropoietin treatment in patients with combined heart and renal failure: objectives and design of the EPOCARES study.

BACKGROUND: Anemia is common in patients with the combination of chronic heart failure and chronic kidney disease and is associated with increased mortality. Recent clinical studies suggest that recombinant human erythropoietin (EPO) treatment has desirable as well as undesirable effects, related to its hematopoietic or nonhematopoietic effects. Therefore a translational study is needed to elucidate mechanistic aspects of EPO treatment. METHODS: In this open-label randomized 12-month trial (the Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome [EPOCARES]), patients with the combination of chronic heart failure and chronic kidney disease (glomerular filtration rate 20-70 ml/min) and mild anemia (hemoglobin 10.3-12.6 g/dL in men, and 10.3-11.9 g/dL in women) are being randomized into 3 groups: 1 group (n=25) receives a fixed dose of 50 IU/kg per week EPO to increase hemoglobin level to a maximum of 13.7 g/dL for men and 13.4 g/dL for women; another group (n=25) is treated with 50 IU/kg per week EPO maintaining baseline hemoglobin levels for the first 6 months by phlebotomy. The control group (n=25) receives standard care without EPO. RESULTS: Cardiac and renal function as well as a panel of biomarkers and iron parameters are being assessed. Furthermore, the effects of EPO on monocyte gene expression profiles and on endothelial progenitor cells are being evaluated. CONCLUSION: This translational study is designed primarily to discern hematopoietic from nonhematopoietic effects of EPO in cardiorenal patients. The study will add insights into the mechanisms that could explain the fragile balance between desirable and undesirable effects of EPO (Trial registration: ClinicalTrials.gov identifier NCT00356733).

Variability of coronary calcium scores throughout the cardiac cycle: implications for the appropriate use of electrocardiogram-dose modulation with retrospectively gated computed tomography.

OBJECTIVE: To study how much the calcium scores at various phases throughout the cardiac cycle deviate from the score in the most motionless phase during retrospectively electrocardiogram (ECG)-gated multidetector row computed tomography (MDCT) of the heart and to evaluate how to optimize ECG-based tube current modulation so that errors in calcium scoring can be minimized while dose savings can be maximized. MATERIALS AND METHODS: In 73 subjects with known or suspected coronary artery disease we performed retrospectively ECG-gated 64-detector row computed tomography for calcium scoring. Four subjects were excluded after scanning because of breathing artifacts or lack of coronary calcification. The scans of 69 subjects (46 men, mean age 62 +/- 6 years) were used for further analysis. Heart rate during the scan was recorded. In each patient, calcium scoring [Agatston score (AS), mass score (MS), and volume score, (VS)] was performed on 10 data sets reconstructed at 10%-intervals throughout the cardiac cycle. The most motionless phase was subjectively determined and used as the reference phase. For the score in each phase, deviation from the score in the reference phase was determined. An ECG-simulator was used to determine the amount of dose saving while scanning with dose modulation and applying diagnostic dose during 1 or several phases. RESULTS: Mean heart rate was 63 (+/-13) beats per minute (bpm). In 51% of patients the reference phase was the 70% phase. Using the calcium score in the 70% phase (mid-diastole) instead of the reference at heart rates below 70 bpm would have induced a median score deviation of 0% [interquartile range: 0%-6% (AS, MS, and VS)] and using the calcium score in the 40% phase (end-systole) at heart rates > or =70 bpm would also have induced a median score deviation of 0% [interquartile range: 0%-7% (AS), 0%-5% (MS), and 0%-3% (VS)]. Errors in calcium scores of more than 10% occur in around 10% of subjects for all 3 scoring algorithms. Dose savings increased with lower heart rates and shorter application of diagnostic dose. CONCLUSIONS: The optimum phases for dose modulation are 70% (mid-diastole) at heart rates below 70 bpm and 40% (end-systole) at heart rates above 70 bpm. Under these conditions dose saving is maximum and a median error of 0% is found for the various calcium scoring techniques with score errors of more than 10% in around 10% of subjects.

Four ECG left ventricular hypertrophy criteria and the risk of cardiovascular events and mortality in patients with vascular disease.

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.

Sympathetic hyperactivity in haemodialysis patients is reduced by short daily haemodialysis.

OBJECTIVE: Haemodialysis patients often have sympathetic hyperactivity. The hypothesis of this study was that a switch from three times weekly to short daily dialysis could affect sympathetic hyperactivity. METHODS: We studied 11 patients (eight men; aged 46 +/- 8 years) stable on haemodialysis for at least 1 year before and 6 months after conversion from three times to six times weekly dialysis without increasing total dialysis time (short daily dialysis). Seven patients were restudied 2 months after switching back to three times weekly haemodialysis. RESULTS: Ultrafiltration volume per session decreased from 2.4 +/- 1.0 to 1.5 +/- 0.6 l (P < 0.05). The extracellular fluid volume (bromide distribution space) did not change. Mean arterial pressure (without medication) decreased from 113 +/- 11 to 98 +/- 9 mmHg (P < 0.05). Cardiac output (Doppler echocardiography) did not change, but peripheral vascular resistance decreased from 25.4 +/- 6.4 to 21.2 +/- 3.2 mmHg per min/l (P < 0.05), in conjunction with a decrease in muscle sympathetic nerve activity (MSNA) from 39 +/- 19 to 28 +/- 15 bursts/min (P < 0.05). Ambulant 24 h blood pressure decreased and the nocturnal blood pressure dip increased during short daily dialysis. The seven patients who were switched back to alternate day haemodialysis showed a return of the high MSNA and peripheral vascular resistance. CONCLUSION: The study shows that sympathetic hyperactivity in haemodialysis patients is reduced by increasing the frequency of treatment sessions. This is probably because of the decrease in number or magnitude of the fluid fluctuations.

Comparison of B-type natriuretic peptide assays for identifying heart failure in stable elderly patients with a clinical diagnosis of chronic obstructive pulmonary disease.

AIMS: To compare the ability of different B-type natriuretic peptide (BNP) assays to identify heart failure in stable elderly patients with a diagnosis of chronic obstructive pulmonary disease (COPD). METHODS: 200 patients aged >or=65 years with COPD according to their general practitioner and without known heart failure, underwent a diagnostic work-up. The final diagnosis of heart failure was established by a panel using the diagnostic principles of the European Society of Cardiology. All available diagnostic results, including echocardiography, but not BNP or NT-proBNP measurements, were used. The ability of different B-type natriuretic peptide assays to identify heart failure was estimated using the area under the receiver operating characteristic curves (ROC-area). RESULTS: The ROC-areas did not differ significantly between the various assays of NT-proBNP and BNP, and ranged from 0.68 (95%CI 0.60-0.73) to 0.73 (95%CI 0.64-0.81). For NT-proBNP the age- and gender-independent 'optimal' cut-point was 15 pmol/l (125 pg/ml) and for BNP 10 pmol/l (35 pg/ml). All assays were much better at excluding than detecting heart failure. CONCLUSIONS: All assays of B-type natriuretic peptide showed reasonable and comparable accuracy in recognising heart failure. At 'optimal' cut-points, all assays performed better at excluding than detecting new cases of heart failure in this population.

Risk Factors for Recurrent Cardiovascular Events Before Age 65 Years or Within 2.5 Years of a Recent First Cardiovascular Event.

The aim of this study was to quantify the relation between classical risk factors (smoking, diabetes, BMI, waist circumference, blood pressure, and lipids), risk factor targets, and risk of recurrent major atherosclerotic cardiovascular events (MACE). This was first done for recurrent MACE ≤65 years in patients aged <60 years and second for recurrent MACE ≤2.5 years after a first cardiovascular event. Data were used from the Second Manifestations of Arterial Disease study (n = 5,115), a prospective cohort of patients with a recent (≤1 year) first cardiovascular event. During follow-up, 746 recurrent MACE occurred. Smoking (hazard ratio [HR] 1.43, 95% CI 1.11 to 1.84), diabetes (HR 1.83, 95% CI 1.11 to 1.84), diastolic blood pressure (>90 vs 70 to 90 mm Hg, HR 1.54, 95% CI 1.15 to 2.07), and high-density lipoprotein cholesterol (≤1.0 vs >1.0 mmol/L, HR 1.34, 95% CI 1.03 to 1.76) were related to increased risk of recurrent MACE ≤65 years in patients aged <60 years. Smoking (HR 1.65, 95% CI 1.23 to 2.22), physical inactivity (highest vs lowest tertile, HR 1.48, 95% CI 1.05 to 2.09), body mass index (per kg/m2, HR 1.04, 95% CI 1.00 to 1.08), diastolic blood pressure (>90 vs 70 to 90 mm Hg, HR 1.61, 95% CI 1.17 to 2.21), low-density lipoprotein cholesterol (per mmol/L, HR 1.18, 95% CI 1.02 to 1.37), and non-high-density lipoprotein cholesterol (per mmol/L, HR 1.15, 95% CI 1.03 to 1.28) were related to recurrent MACE ≤2.5 years of follow-up. In conclusion, in patients with a recent cardiovascular event, smoking, blood pressure, and lipids are related to increased risk of recurrent cardiovascular events at young age or within a short time span, and intensive treatment of modifiable risk factors may contribute to prevent recurrent MACE in these patients.

Identification of the Asymptomatic Patient With Severe Mitral Regurgitation: Discrepancy Between Research and Clinical Practice.

Organic mitral regurgitation (MR) is a common disorder, and because of the increase in population and its aging, the occurrence of MR is steadily increasing. Current guideline recommendations on the management of asymptomatic severe MR are conflicting and based solely on registries or nonrandomized trials in expert heart valve clinics, resulting in a lack of evidence for the best treatment strategy. In this review, we will evaluate the latest evidence on diagnostic approaches and treatment strategies for asymptomatic patients without a clear indication for surgical intervention. Implications for management in daily practice are discussed, including an update on the diagnostic approaches that are currently available for the evaluation of MR. For optimal care, it is important that every severe MR patient, including the unidentified patient, is referred to a specialized heart team and is assessed on an individual basis according to the guideline recommendations, experience of the surgical center, and the patient's characteristics and preferences. Screening and diagnostic approaches need to be performed on the basis of standardized protocols and strict criteria. In addition, specialized valve centers must meet the surgical criteria to guarantee high reparability rates in asymptomatic patients. Awareness among cardiologists and cardiothoracic surgeons, improved guidelines adherence, and a systematic approach, including strict criteria in the management of asymptomatic patients with severe organic MR, will ensure reliable and applicable results in research and daily clinical practice.

Heart failure and chronic obstructive pulmonary disease: An ignored combination?

AIMS: To quantify the prevalence of heart failure and left ventricular systolic dysfunction (LVSD) in chronic obstructive pulmonary disease (COPD) patients and vice versa. Further, to discuss diagnostic and therapeutic implications of the co-existence of both syndromes. METHODS AND RESULTS: We performed a Medline search from 1966 to March 2005. The reported prevalence of LVSD among COPD patients varied considerably, with the highest prevalence (10-46%) among those with an exacerbation. One single study assessed the prevalence of heart failure in COPD patients. A prevalence of 21% of previously unknown heart failure was reported in patients with a history of COPD or asthma. We did not find any report on COPD in heart failure or LVSD patients. Diagnosing heart failure in COPD patients or vice versa is complicated by overlap in signs and symptoms, and diminished diagnostic value of additional investigations. In general, pulmonary and heart failure 'drug cocktails' can be administered safely to patients with concomitant COPD and heart failure, although (short acting) beta2-adrenoreceptor agonists and digitalis have potentially deleterious effects on cardiac and pulmonary function, respectively. CONCLUSION: Although knowledge about the prevalence of concomitant heart failure in COPD patients and vice versa is scarce, it seems that the combined presence is rather common. In view of diagnostic and therapeutic implications, more attention should be paid to the concomitant presence of both syndromes in clinical practice and research.

Familial occurrence of isolated non-compaction cardiomyopathy.

BACKGROUND AND AIMS: Isolated left ventricular non-compaction cardiomyopathy (LVNC) may have an autosomal dominant or X-linked recessive inheritance. We focus on the familial occurrence of LVNC after misdiagnosing this disorder in symptomatic patients in two families. After identification of the index patient we studied the families more intensively in order to unmask affected family members. METHODS AND RESULTS: LVNC was defined as an end-systolic non-compacted subendocardial layer of the left ventricular wall of at least twice the thickness of the subepicardial compacted layer (2D echocardiogram and MRI). This was studied in 13 patients in 2 families (A and B). LVNC was found in 3 out of 11 patients in family A. The grandmother was asymptomatic. Her daughter suffered from recurrent syncope and heart failure. Her daughter received a cardiac transplant because of progressive heart failure at the age of 14years. In family B, LVNC was found in 2 patients, a father and his son and presumed in a brother and a sister of the father who died suddenly at the age of 17 and 21years, respectively. CONCLUSIONS: In all symptomatic patients, proven LVNC was previously misdiagnosed as hypertrophic or dilated cardiomyopathy. Misdiagnosis may lead to insufficient treatment and will misdirect targeted molecular genetic analysis. LVNC was identified in seven patients in two families. Family screening may unmask affected family members for primary prevention including anti-coagulation and ICD-therapy.

Myocardial blood supply by left ventricle-to-coronary artery channel: an old idea revisited.

Coronary artery disease is one of the most important causes of death in Western society. Attempts to revascularize the coronary artery by myocardial retroperfusion, direct revascularization from the left ventricle, and bypass surgery have finally led to percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) as standard treatment for coronary artery disease. Direct revascularization from the left ventricle has already been studied in the late 1960s, but the idea was rejected because of a decrease in flow in combination with a failure of myocardial function. Recently, a left ventricle-to-coronary artery (LV-CA) stent has renewed interest as an alternative procedure when PTCA and CABG are no option. Animal studies showed a change in flow pattern from diastolic coronary inflow at baseline to systolic coronary inflow followed by diastolic regurgitive flow during direct ventricular sourcing, resulting in a coronary flow of 50-75% of baseline flow. Global myocardial function decreased in the same extent as the coronary flow suggesting perfusion-contraction matching. In a recent pilot study in the anaesthetized pig, direct revascularization after acute proximal coronary ligation resulted in sufficient blood supply to the outer layers of the myocardium, however, in the inner layers a metabolic disbalance occurred. Incorporation of a valve-like mechanism to minimize the diastolic regurgitive flow may be necessary to improve the performance of the LV-CA stent. In addition, further research should be done in chronic ischemic animal models in which the effect of the collateral circulation on myocardial perfusion and performance is an important issue.

Colour M-mode velocity propagation: a glance at intra-ventricular pressure gradients and early diastolic ventricular performance.

The physiology of early-diastolic filling comprises ventricular performance and fluid dynamical principles. Elastic recoil and myocardial relaxation rate determine left ventricular early diastolic performance. The integrity of left ventricular synchrony and geometry is essential to maintain the effect of their timely action on early diastolic left ventricular filling. These factors not only are prime determinants of left ventricular pressure decay during isovolumic relaxation and immediately after mitral valve opening; they also instigate the generation of a sufficient intra-ventricular pressure gradient, which enhances efficient early diastolic left ventricular filling. Accurate assessment of diastolic (dys)function by non-invasive techniques has important therapeutic and prognostic implications but remains a challenge to the cardiologist. The evaluation of left ventricular relaxation by the standard Doppler echocardiographic parameters is hindered by their preload dependency. The colour M-mode velocity propagation of early diastolic inflow (Vp) correlates with intra-ventricular pressure gradients and is a largely preload independent index of ventricular diastolic performance. In this article, the physiologic background, utility and limitations of this promising new tool for the study of early diastolic filling are reviewed.

Staged decision making was an attractive alternative to a plenary approach in panel diagnosis as reference standard.

OBJECTIVES: To assess differences between three different decision-making approaches in the method of panel diagnosis as reference standard in diagnostic research. STUDY DESIGN AND SETTING: Within a diagnostic study, the prevalence of heart failure (HF) and chronic obstructive pulmonary disease (COPD) was compared using three approaches of decision making in panel diagnosis. These were (1) a plenary discussion among experts followed by a consensus decision (plenary); (2) a predefined decision rule based on final diagnoses made by each member individually (individual); and (3) a staged procedure in which first the final diagnosis per individual member is generated followed by a plenary discussion of those cases with disagreement (staged). RESULTS: Prevalence of HF and COPD according to plenary approach was 46% and 28%, respectively. Individual approach diagnosed 28% of patients with HF and 31% with COPD and revealed 28 and 8 discordant diagnoses, respectively, compared with plenary approach. Staged approach revealed a prevalence of 43% and 28% for HF and COPD, respectively, with eight discordant diagnoses for HF and none for COPD. CONCLUSION: The staged approach is an attractive choice as it produces very similar results to the full plenary approach, while having the advantage of being less time consuming. Additionally, it provides insights into the decision-making process of the panel, and the "difficult-to-diagnose" patients can easily be identified.

Spectral pulsed tissue Doppler imaging in diastole: a tool to increase our insight in and assessment of diastolic relaxation of the left ventricle.

BACKGROUND: Conventional Doppler echocardiography offers an indirect assessment of left ventricular (LV) diastolic function, hampered by preload dependency. Tissue Doppler imaging (TDI) is a tool to study diastolic function in a more direct and less preload-dependent manner. METHODS: The Medline database has been searched for literature on TDI for the analysis of diastolic function. A secondary search reviewed the relevant references related to TDI or diastolic function in general. RESULTS: TDI measures myocardial velocities with a high temporal and velocity resolution but lacks spatial information. In particular, the velocity of early diastolic wall motion (E(m)) and its timing are promising indices of local myocardial relaxation. E(m) at the mitral annulus offers fair estimates of ventricular relaxation, relatively independent of preload and systolic function. Combined with early transmitral flow velocity (E), detection of pseudo-normalized filling patterns and estimation of filling pressures are enhanced by E/E(m). CONCLUSION: TDI has an emerging role in the study and assessment of diastolic function. However, TDI-derived information needs to be integrated with other echocardiographic data because single diagnostic accuracy remains unsatisfactory.