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Objective To evaluate the effect of heart rate reduction by ivabradine on coronary collateral function in patients with chronic stable coronary artery disease (CAD). Methods This was a prospective randomised placebo-controlled monocentre trial in a university hospital setting. 46 patients with chronic stable CAD received placebo (n=23) or ivabradine (n=23) for the duration of 6 months. The main outcome measure was collateral flow index (CFI) as obtained during a 1 min coronary artery balloon occlusion at study inclusion (baseline) and at the 6-month follow-up examination. CFI is the ratio between simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. Results During follow-up, heart rate changed by +0.2±7.8 beats/min in the placebo group, and by –8.1±11.6 beats/min in the ivabradine group (p=0.0089). In the placebo group, CFI decreased from 0.140±0.097 at baseline to 0.109±0.067 at follow-up (p=0.12); it increased from 0.107±0.077 at baseline to 0.152±0.090 at follow-up in the ivabradine group (p=0.0461). The difference in CFI between the 6-month follow-up and baseline examination amounted to −0.031±0.090 in the placebo group and to +0.040±0.094 in the ivabradine group (p=0.0113). Conclusions Heart rate reduction by ivabradine appears to have a positive effect on coronary collateral function in patients with chronic stable CAD. ClinicalTrials.gov Identifier: NCT01039389.

Objective This study tested the hypotheses that intermittent coronary sinus occlusion (iCSO) reduces myocardial ischaemia, and that the amount of ischaemia reduction is related to coronary collateral function. Design Prospective case-control study with intraindividual comparison of myocardial ischaemia during two 2-min coronary artery balloon occlusions with and without simultaneous iCSO by a balloon-tipped catheter. Setting University Hospital. Patients 35 patients with chronic stable coronary artery disease. Intervention 2-min iCSO. Main outcome measures Myocardial ischaemia as assessed by intracoronary (i.c.) ECG ST shift at 2 min of coronary artery balloon occlusion. Collateral flow index (CFI) without iCSO, that is, the ratio between mean distal coronary occlusive (P occl ) and mean aortic pressure (P ao ) both minus central venous pressure. Results I.c. ECG ST segment shift (elevation in all) at the end of the procedure with iCSO versus without iCSO was 1.33±1.25 mV versus 1.85±1.45 mV, p 2 =0.61). Ischaemia reduction with iCSO was greatest at a CFI of 0.05–0.20, whereas in the low and high CFI range the effect of iCSO was absent. Conclusions ICSO reduces myocardial ischaemia in patients with chronic coronary artery disease. Ischaemia reduction by iCSO depends on coronary collateral function. A minimal degree of collateral function is necessary to render iCSO effective. ICSO cannot manifest an effect when collateral function prevents ischaemia in the first place. ClinicalTrials.gov Identifier NCT01625832.

To test whether quantitative stress echocardiography using contrast-based myocardial blood flow (MBF, ml x min(-1) x g(-1)) measurements can detect coronary artery disease in humans.48 patients eligible for pharmacological stress testing by myocardial contrast echocardiography (MCE) and willing to undergo subsequent coronary angiography were prospectively enrolled in the study. Baseline and adenosine-induced (140 microg x kg(-1) x min(-1)) hyperaemic MBF was analysed according to a three-coronary-artery-territory model. Vascular territories were categorised into three groups with increasing stenosis severity defined as percentage diameter reduction by quantitative coronary angiography.Myocardial blood flow reserve (MBFR)-that is, the ratio of hyperaemic to baseline MBF, was obtained in 128 (89%) territories. Mean (SD) baseline MBF was 1.073 (0.395) ml x min(-1) x g(-1) and did not differ between territories supplied by coronary arteries with mild (50% stenosis), moderate (50%-74% stenosis) or severe (or=75% stenosis) disease. Mean (SD) hyperaemic MBF and MBFR were 2.509 (1.078) ml x min(-1) x g(-1) and 2.54 (1.03), respectively, and decreased linearly (r2 = 0.21 and r2 = 0.39) with stenosis severity. ROC analysis revealed that a territorial MBFR1.94 detectedor=50% stenosis with 89% sensitivity and 92% specificity.Quantitative stress testing based on MBF measurements derived from contrast echocardiography is a new method for the non-invasive and reliable assessment of coronary artery disease in humans.

Background: Patients may develop dual-loop re-entrant atrial arrhythmias late after open-heart surgery, and mapping and catheter ablation remain challenging despite computer-assisted mapping techniques. Objectives: The purpose of the study was to demonstrate the prevalence and characteristics of dual-loop re-entrant arrhythmias, and to define the optimal mapping and ablation strategy. Methods: 40 consecutive patients (mean (SD) age 52 (12) years) with intra-atrial re-entrant tachycardia (IART) after open-heart surgery (with an incision of the right atrial free wall) were studied. Dual-loop IART was defined as the presence of two simultaneous atrial circuits. After an abrupt tachycardia change during radiofrequency ablation, electrical disconnection of the targeted re-entry isthmus from the remaining circuit was demonstrated by entrainment mapping. Furthermore, the second circuit loop was localised using electroanatomical mapping and/or entrainment mapping. Results: Dual-loop IART was demonstrated in eight (20%, 5 patients with congenital heart disease, 3 with acquired heart disease) patients. Dual-loop IART included an isthmus-dependant atrial flutter combined with a re-entry related to the atriotomy scar. The diagnosis of dual-loop IART required the comparison of entrainment mapping before and after tachycardia modification. Overall, 35 patients had successful radiofrequency ablation (88%). Success rates were lower in patients with dual-loop IART than in patients without dual-loop IART. Ablation failures in three patients with dual-loop IART were related to the inability to properly transect the second tachycardia isthmus in the right atrial free wall. Conclusions: Dual-loop IART is relatively common after heart surgery involving a right atriotomy. Abrupt tachycardia change and specific entrainment mapping manoeuvres demonstrate these circuits. Electroanatomical mapping appears to be important to assist catheter ablation of periatriotomy circuits.

Objective: To test the hypothesis that regional left ventricular (LV) function during balloon angioplasty is related to the amount of collateral flow to the ischaemic region. Design: Prospective study. Setting: Tertiary referral centre. Methods: In 50 patients with coronary artery disease and without myocardial infarction, regional systolic and diastolic LV function was determined using tissue Doppler ultrasound (TD) before and at the end of a 60 second occlusion of a stenotic lesion undergoing percutaneous transluminal coronary angioplasty (PTCA) through a pressure guidewire. The study population was subdivided into a group with collaterals insufficient (n = 33) and one with collaterals sufficient (n = 17) to prevent ECG ST shifts suggestive of myocardial ischaemia during PTCA. Pulsed TD was performed from an apical window in the myocardial region supplied by the vessel being treated by PTCA. Pressure derived collateral flow index (CFI) was determined by simultaneous measurement of mean aortic (P ao ) and distal intracoronary occlusive pressures (P occl ), where CFI = (P occl − 8)/(P ao − 8). Results: At 60 seconds of occlusion, several parameters of systolic and diastolic TD derived LV long axis function were significantly different between the groups. Also, there was a significant correlation between regional systolic excursion velocity, early diastolic excursion velocity, regional isovolumetric relaxation time, and CFI. Conclusion: During brief coronary artery occlusions, regional systolic and diastolic LV function is directly related to the amount of collateral flow to this territory.

OBJECTIVE—To determine whether myocardial contrast echocardiography can be used to quantify collateral derived myocardial flow in humans. METHODS—In 25 patients undergoing coronary angioplasty, a collateral flow index (CFI) was determined using intracoronary wedge pressure distal to the stenosis to be dilated, with simultaneous mean aortic pressure measurements. During balloon occlusion, echo contrast was injected into both main coronary arteries simultaneously. Echocardiography of the collateral receiving myocardial area was performed. The time course of myocardial contrast enhancement in images acquired at end diastole was quantified by measuring pixel intensities (256 grey units) within a region of interest. Perfusion variables, such as background subtracted peak pixel intensity and contrast transit rate, were obtained from a fitted γ variate curve. RESULTS—16 patients had a left anterior descending coronary artery stenosis, four had a left circumflex coronary artery stenosis, and five had a right coronary artery stenosis. The mean (SD) CFI was 19 (12)% (range 0-47%). Mean contrast transit rate was 11 (8) seconds. In 17 patients, a significant collateral contrast effect was observed (defined as peak pixel intensity more than the mean + 2 SD of background). Peak pixel intensity was linearly related to CFI in patients with a significant contrast effect (p = 0.002, r = 0.69) as well as in all patients (p = 0.0003, r = 0.66). CONCLUSIONS—Collateral derived perfusion of myocardial areas at risk can be demonstrated using intracoronary echo contrast injections. The peak echo contrast effect is directly related to the magnitude of collateral flow. Keywords: collateral circulation; quantitative myocardial contrast echocardiography; intracoronary pressure; myocardial perfusion

OBJECTIVE—To evaluate recent changes in the spectrum and clinical presentation of infective endocarditis and to determine predictors of outcome. DESIGN—A retrospective case study. METHODS—Demographic, clinical, and echocardiographic characteristics were examined in 212 patients who fulfilled the Duke criteria for infective endocarditis between January 1980 and December 1995 to assess changes in clinical presentation and survival. RESULTS—Clinical presentation and course did not change significantly during the study period despite the concurrent introduction of new diagnostic tools (for example, transoesophageal echocardiography). In-hospital mortality was 15% and remained unchanged. Neurological symptoms on admission, arthralgia, and weight loss were all independent risk factors for adverse outcome (odds ratios 26.1, 6.2, and 4.2, respectively). Age, prosthetic valve disease, previous antibiotic treatment, renal insufficiency, surgical treatment, and the type of valve involved were not predictive of mortality. In contrast to all other major reports, Streptococcus viridans was the most common causative organism in intravenous drug users (52%). CONCLUSIONS—Despite the introduction of new diagnostic tools, the course of infective endocarditis has remained unchanged over a period of 16 years. Evidence of early dissemination of the disease to other sites was associated with adverse outcome. Even in elderly patients, early aggressive treatment seems to be effective. Keywords: infective endocarditis; outcome; prognostic factors

AIM—To determine the relation between the extent and distribution of left ventricular hypertrophy and the degree of disturbance of regional relaxation and global left ventricular filling. METHODS—Regional wall thickness (rWT) was measured in eight myocardial regions in 17 patients with hypertrophic cardiomyopathy, 12 patients with hypertensive heart disease, and 10 age matched normal subjects, and an asymmetry index calculated. Regional relaxation was assessed in these eight regions using regional isovolumetric relaxation time (rIVRT) and early to late peak filling velocity ratio (rE/A) derived from Doppler tissue imaging. Asynchrony of rIVRT was calculated. Doppler left ventricular filling indices were assessed using the isovolumetric relaxation time, the deceleration time of early diastolic filling (E-DT), and the E/A ratio. RESULTS—There was a correlation between rWT and both rIVRT and rE/A in the two types of heart disease (hypertrophic cardiomyopathy: r = 0.47, p

BACKGROUND—The severity of aortic regurgitation can be estimated using pressure half time (PHT) of the aortic regurgitation flow velocity, but the correlation between regurgitant fraction and PHT is weak. AIM—To test the hypothesis that the association between PHT and regurgitant fraction is substantially influenced by left ventricular relaxation. METHODS—In 63 patients with aortic regurgitation, subdivided into a group without (n = 22) and a group with (n = 41) left ventricular hypertrophy, regurgitant fraction was calculated using the difference between right and left ventricular cardiac outputs. Left ventricular relaxation was assessed using the early to late diastolic Doppler tissue velocity ratio of the mitral annulus (E/ADTI), the E/A ratio of mitral inflow (E/AM), and the E deceleration time (E-DT). Left ventricular hypertrophy was assessed using the M mode derived left ventricular mass index. RESULTS—The overall correlation between regurgitant fraction and PHT was weak (r = 0.36, p

OBJECTIVES: The purpose of the present study in patients with severe aortic stenosis was to assess the prevalence of absent left ventricular hypertrophy (LVH) (determined according to mass criteria), to identify predictors of absent LVH, and to assess short-term left ventricular adaptation and prognosis after aortic valve replacement. METHODS: Left ventricular mass (LVM) was determined by echocardiography in 109 men and 101 women with severe aortic stenosis (mean pressure gradient < or = 50 mm Hg). LVH was defined as LVM > or = 109 g/m2 in women and LVM > or = 134 g/m2 in men. RESULTS: One hundred and eighty nine patients showed LVH (group 1) (90%; mean (SD) age 65 (14) years), and 21 showed no LVH (group 2) (10%, age 57 (21) years P = 0.02 for difference in age). Twelve (6%) of those without LVH had increased relative wall thickness (that is, > or = 0.45 with LV concentric remodelling) and nine (4%) showed no macroscopically detectable hypertrophic adaptation. The following variables were associated with the absence of LVH: low body surface area, low body mass index, and increased cardiac index. 76/210 patients were followed up a mean of six months after aortic valve replacement. The frequency of adequate ventricular adaptation to the decreased afterload after aortic valve replacement was higher in patients with LVH than in those without. Mortality six months after aortic valve replacement was lower, but not significantly, in patients with LVH (7.6%) than in those without LVH (12.5%, P = 0.10). CONCLUSIONS: A tenth of patients with severe aortic stenosis did not develop LVH according to mass criteria; 4% of the patients did not have any macroscopic signs of myocardial adaptation to the pressure overload despite longstanding disease. Small body size was independently associated with lack of LVH according to mass criteria. Six months after aortic valve replacement, ventricular adaptation was more often adequate in patients with LVH than in those without.