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Introduction Function of naturally existing internal mammary artery (IMA)-to-coronary artery anastomoses has been shown by augmented blood supply to the coronary collateral circulation in response to IMA occlusion. Theoretically, this functional connection is invertible and can cause coronary steal, the verification of whose hypothesis would provide alternate proof to the mentioned functional evidence. Method This was a prospective observational study including 40 patients with chronic coronary syndrome and IMA occlusion, and 40 propensity score matched controls (placebo group) without IMA occlusion. Primary study endpoint was the inter-group difference in coronary collateral function (i.e., collateral flow index, CFI) as obtained at 30, 45 and 60 seconds following a proximal coronary artery balloon occlusion. CFI is the ratio between simultaneous mean coronary occlusive pressure divided by mean aortic pressure both subtracted by central venous pressure. To provoke a steal phenomenon, upper limb hyperemia was induced by upper arm blood pressure cuff deflation following a 5-minute supra-systolic inflation ipsilateral to the sensor-wired coronary artery with release immediately after the first CFI measurement. Results Between the first and the second CFI-measurement, CFI change (i.e., CFI@45s minus CFI@30s) was absent in the verum group while there was CFI recruitment in the placebo group: 0.000±0.023 and +0.009±0.013, respectively; p=0.032. Conclusion Among patients with artificial IMA occlusion, induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal as expressed by temporarily absent collateral recruitment as it normally takes place without upper limb hyperemia. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Sciences Foundation

BACKGROUND Inferolateral early repolarization (ER) is associated with an increase in arrhythmic risk, particularly in the presence of myocardial ischemia. OBJECTIVE To determine the effect of myocardial ischemia on ER. METHODS We retrospectively analyzed procedural ECGs of patients with ER undergoing a controlled, 1-minute coronary occlusion for collateral function testing. ECG leads with ER were analyzed before (PRE), at 60 seconds of coronary balloon occlusion (OCCL) and >30 seconds after balloon deflation (POST). RESULTS Seventy-seven patients with ER in the pre-procedural ECG (86% inferior, 20% lateral) underwent 135 coronary balloon occlusions during which a J wave was recorded in 224 leads (ER leads). From PRE to OCCL, ST-segment amplitude (ST) in the ER lead increased in 94 (44%) cases from 0.00±0.03 mV to 0.05±0.06 mV (p

Change in the dynamics of single-stranded DNA or RNA probes tethered to an Au electrode on immunospecific binding to the analyte is a versatile approach to quantify a variety of molecules, such as heavy metal ions, pesticides, proteins, and nucleic acids (NAs). A widely studied approach is the electrochemical beacon method where the redox of a dye attached to the probe decreases as its proximity to the underlying electrode changes on binding. The limit of quantification (LOQ) defined by the semilog dependence of the signal on target concentration is in the picomolar range. Here, a method was studied where, by differential reflectivity, multiple reactions were measured on a monolith electrode. An alternative contrast mechanism was discovered, which led to an approach to enhance the LOQ to 10 aM and increase the dynamic range to 7 orders of magnitude using similar probes and binding conditions. Quantitative analysis on sequences with the G-C fraction ranging from 37 to 72% was performed. The approach will allow for the development of a label-free, enzyme-free microarray to detect biomolecules including NAs and proteins on a single electrode at quantification from 10 aM to 0.1 nM with high specificity.

Introduction In patients with chronic coronary syndrome, percutaneous coronary intervention targets haemodynamically significant stenoses, that is, those thought to cause ischaemia. Intracoronary ECG (icECG) detects ischaemia directly where it occurs. Thus, the goal of this study was to test the accuracy of icECG during pharmacological inotropic stress to determine functional coronary lesion severity in comparison to the structural parameter of quantitative angiographic per cent diameter stenosis (%S), as well as to the haemodynamic indices of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR).Method The primary study endpoint of this prospective trial was the maximal change in icECG ST-segment shift during pharmacological inotropic stress induced by dobutamine plus atropine obtained within 1 min after reaching maximal heart rate(=220 - age). IcECG was acquired by attaching an alligator clamp to the angioplasty guidewire positioned downstream of the stenosis. For the pressure-derived stenosis severity ratios, coronary perfusion pressure and simultaneous aortic pressure were continuously recorded.Results There was a direct linear relation between icECG ST-segment shift and %S: icECG=−0.8+0.03*%S (r2=0.164; p

Background Natural, nonsurgical internal mammary artery (IMA) bypasses to the coronary circulation have been shown to function as extracardiac sources of myocardial blood supply. The goal of this randomized, placebo-controlled, double-blind trial was to test the efficacy of permanent right IMA (RIMA) device occlusion on right coronary artery (RCA) occlusive blood supply and on clinical and electrocardiographic (ECG) signs of myocardial ischemia. Methods This was a prospective superiority trial in 100 patients with chronic coronary artery disease randomly allocated (1:1) to RIMA vascular device occlusion (verum group) or to RIMA sham procedure (placebo group). The primary study end point was RCA collateral flow index (CFI) as obtained during a 1-minute ostial RCA balloon occlusion at baseline before and at follow-up examination 6 weeks after the trial intervention. CFI is the ratio between simultaneous mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure. Simultaneously obtained secondary study end points were the registration of angina pectoris and quantitative intracoronary ECG ST-segment shift. Results CFI change during the follow-up period was +0.036 ± 0.068 in the verum group and −0.021 ± 0.097 in the placebo group (P = .0011). Angina pectoris during the same RCA balloon occlusions had disappeared at follow-up in 14/49 patients of the verum group and in 4/49 patients of the placebo group (P = .0091). Simultaneous intracoronary ECG ST-segment shift change revealed diminished myocardial ischemia at follow-up in the verum group and more severe ischemia in the placebo group. Conclusions Permanent RIMA device occlusion augments RCA supply to the effect of diminishing clinical and electrocardiographic signs of myocardial ischemia during a brief controlled coronary occlusion.

BACKGROUND The outcome of patients undergoing percutaneous coronary interventions (PCIs) varies considerably. Several ECG parameters have recently emerged (PQ interval, P-wave, T-peak-to-T-end interval, T-wave, T/R ratio, J-wave) beyond traditional markers (rhythm, QRS, Q-wave, QT interval, ST segment) and were attributed important prognostic value in the setting of coronary artery disease. The present study integrated for the first time these ECG parameters altogether with the aim to determine their role in predicting patients' outcome after a PCI. METHODS A total of 3342 patients were enrolled in the present study between 2009 and 2013. In a nested case-control design, 644 patients who died within a year post-PCI (cases) were matched 1:4 with patients alive at that particular date (controls). RESULTS Our data showed that only the presence of a longer QT interval (heart rate-corrected using Bazett formula) was associated with increased risk of death after adjusting for multiple clinical and angiographic risk factors (adjusted OR 1.07; 95%CI 1.01-1.12, p = .022). CONCLUSION Our study emphasises the prognostic importance of the QT interval in identifying patients at increased risk of death during the first year after PCI. Clinical Trial Registration - URL: https://www.clinicaltrials.gov . Unique identifier: NCT02241291.

Background Extracardiac coronary artery supply via the pericardiophrenic branch of the internal mammary arteries (IMA) has been well documented anatomically. Recently, a proof-of-concept study has found functional relevance of these anastomoses in patients with coronary artery disease (CAD) during a brief right coronary artery (RCA) occlusion. Purpose The aim of the present randomized controlled, single-blind trial was to investigate the effect of permanent right IMA (RIMA) occlusion on RCA collateral flow index (CFI) and on the occurrence of angina pectoris. We hypothesized that the change in RCA CFI from baseline to follow-up examination is higher in the group of patients with than without permanent RIMA occlusion. Methods One hundred patients with CAD were randomly allocated (1:1) to permanent RIMA device occlusion at baseline or to no RIMA occlusion (sham control group). The primary study endpoint was CFI change in the RCA from baseline to the 6-week follow-up examination. CFI is the ratio between mean coronary occlusive and aortic pressure both subtracted by central venous pressure as obtained during a 1-minute proximal RCA balloon occlusion. RCA CFI was measured at baseline before RIMA occlusion or the sham procedure and at the follow-up invasive exam. At the end of the same occlusion, occurrence of angina pectoris was assessed. Percutaneous coronary intervention (PCI) of the RCA was deferred until after follow-up RCA CFI measurement. Results There were 51 patients in the RIMA occlusion (verum) group and 49 patients in the sham control group. PCI in the left coronary territory was performed at baseline for clinical reasons in 27 patients of the verum group and in 25 patients of the sham control group. There were no differences in clinical characteristics at baseline between the groups (age 68±12 years, 88 men). RCA CFI change during the 6 weeks of follow-up was equal to +0.028±0.077 in the verum group and −0.026±0.079 in the sham control group (p=0.0017). Angina pectoris during CFI measurement had disappeared at follow-up exam in 30% of the verum group and in 2% of the sham control group (p=0.0013). Conclusions Right coronary collateral function is augmented 6 weeks after permanent RIMA occlusion when compared to sham treatment. This manifests as less frequent angina pectoris during myocardial ischemia among patients with RIMA occlusion. Acknowledgement/Funding This study was supported by a grant from the Swiss National Science Foundation for Research (grant #32003B_163256/1 to CS).

Purpose This paper aims to analyze and understand the changes in the academic library collection landscape since the Janus Conference in 2005. Design/methodology/approach This paper is reflective, reviewing the outcomes of the Janus Conference and providing a careful analysis of the library collection landscape that has evolved since. Findings Dramatic changes in both library funding and the organization of the scholarly environment have required significant changes to the way one thinks of the library collections and their relation with one another. Originality/value This paper provides a new perspective on the nature of the research librarian and his/her relationship to the building of library collections and the provision of access to them.

Background: The present study aimed to quantitatively measure the pressure-derived function of the palmar arch and forearm arterial collateral circulation during transradial access. Methods and Results: Palmar arch and forearm collateral function was determined using radial artery pressure signals in the nonobstructed vessel and during brief manual occlusions of the more proximal radial artery and of the radial plus ulnar arteries. Collateral flow index (CFI), the ratio of mean occlusive divided by mean nonocclusive arterial blood pressure, both subtracted by central venous pressure, was determined for CFI during radial artery occlusion (CFI rad ) and CFI during radial plus ulnar artery occlusion. Before invasive CFI measurements, arterial palmar arch and forearm function was tested noninvasively by the modified Allen test (MAT). Two hundred fifty patients undergoing transradial access coronary angiography were included in the study. CFI rad was equal to 0.802±0.150 (95% CI, 0.783–0.820). CFI during radial plus ulnar artery occlusion was equal to 0.424±0.188 (95% CI, 0.400–0.447). There was an inverse linear relation between CFI rad and MAT in seconds (s): MAT=64−63×CFI rad ( r 2 =0.229; P 15 seconds) MAT. The group with normal MAT had a CFI rad of 0.830±0.111, and patients with abnormal MAT had a CFI rad of 0.648±0.224 ( P Conclusions: Direct invasive hemodynamic assessment of the palmar arch and forearm arterial function reveals collateral supply to the briefly occluded in comparison to the patent radial artery of 0.802. During external occlusion of both radial and ulnar artery, CFI amounts to an unexpectedly high value of 0.424.

Objective To test the effect of long-term pegfilgrastim on collateral function and myocardial ischaemia in patients with chronic stable coronary artery disease (CAD). Methods This was a prospective clinical trial with randomized 2:1 allocation to pegfilgrastim or placebo for 6 months. The primary study endpoint was collateral flow index (CFI) as obtained during a 1-minute ostial coronary artery balloon occlusion. CFI is the ratio of mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure (mm Hg/mm Hg). Secondary endpoints were signs of myocardial ischaemia determined during the same coronary occlusion, that is quantitative intracoronary (i.c.) ECG ST-segment shift (mV) and the occurrence of angina pectoris. Endpoints were obtained at baseline before and at follow-up after three subcutaneous study drug injections. Results Collateral flow index in the pegfilgrastim group changed from 0.096 ± 0.076 at baseline to 0.126 ± 0.070 at follow-up (P = 0.0039), while in the placebo group CFI changed from 0.157 ± 0.146 to 0.122 ± 0.043, respectively (P = 0.29); the CFI increment at follow-up was +0.030 ± 0.075 in the pegfilgrastim group and -0.034 ± 0.148 in the placebo group (P = 0.0172). In the pegfilgrastim group, i.c. ECG ST-segment shift changed from +1.23 ± 1.01 mV at baseline to +0.93 ± 0.97 mV at follow-up (P = 0.0049), and in the placebo group, it changed from +0.98 ± 1.02 mV to +1.43 ± 1.09 mV, respectively (P = 0.05). At follow-up, the fraction of patients free from angina pectoris during coronary occlusion had increased in the pegfilgrastim but not in the placebo group. Conclusion Pegfilgrastim given over the course of 6 months improves collateral function in chronic stable CAD, which is reflected by reduced myocardial ischaemia during a controlled coronary occlusion.

AIMS In this study we aimed to test the hypothesis that left ventricular (LV) afterload reduction in severe aortic valve stenosis (AS) by transcatheter aortic valve implantation (TAVI) acutely improves coronary haemodynamics. METHODS AND RESULTS This was a prospective, pathophysiologic study in 40 patients with severe AS undergoing TAVI. Endpoints were determined invasively immediately before and after TAVI without altering coronary stenotic lesions if present. Myocardial hyperaemia was induced by intravenous adenosine. The primary study endpoints were coronary flow reserve (thermodilution-derived CFR), and fractional flow reserve (FFR). The secondary study endpoint was coronary collateral flow index (CFI) as obtained during a one-minute coronary balloon occlusion. CFR was 1.9±0.9 before TAVI and 2.0±1.0 after TAVI (p=0.72). FFR was 0.90±0.08 before TAVI and 0.93±0.08 after TAVI (p=0.0021). The TAVI-induced increase in FFR was related to a significant decrease in hyperaemic mean aortic pressure from 71±16 mmHg before TAVI to 67±15 mmHg after TAVI (p=0.0099). Hyperaemic CFI increased from 0.127±0.083 before to 0.146±0.090 after TAVI (p=0.0508). CONCLUSIONS CFR appears not to be acutely affected by LV afterload reduction among patients with severe AS in response to TAVI. However, it acutely improves FFR; this occurs via lowering of mean aortic pressure. Hyperaemic coronary collateral flow index tends to augment in response to TAVI.

The intraindividual variability and association of human collateral functional supply to different arterial regions is unknown. The primary study end point was collateral flow index (CFI) as obtained in the coronary artery (CA), renal artery (RA), left superficial femoral artery (SFA), and left subclavian artery (SCA) of the same individual. CFI is the ratio between simultaneously recorded mean arterial occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. In 100 patients admitted for diagnostic coronary angiography, CFI was assessed in 3 arterial regions (CA, RA, and SFA), 13 patients underwent CFI measurements in all 4 territories. By quantitative coronary angiography, 82 patients had a stenosis

Arterial waves are seen as possible independent mediators of cardiovascular risks, and the wave intensity analysis (WIA) has therefore been proposed as a method for patient selection for ventricular assist device (VAD) implantation. Interpreting measured wave intensity (WI) is challenging, and complexity is increased by the implantation of a VAD. The waves generated by the VAD interact with the waves generated by the native heart, and this interaction varies with changing VAD settings. Eight sheep were implanted with a pulsatile VAD (PVAD) through ventriculoaortic cannulation. The start of PVAD ejection was synchronized to the native R wave and delayed between 0 and 90% of the cardiac cycle in 10% steps or phase shifts (PS). Pressure and velocity signals were registered, with the use of a combined Doppler and pressure wire positioned in the abdominal aorta, and used to calculate the WI. Depending on the PS, different wave interference phenomena occurred. Maximum unloading of the left ventricle (LV) coincided with constructive interference and maximum blood flow pulsatility, and maximum loading of the LV coincided with destructive interference and minimum blood flow pulsatility. We believe that noninvasive WIA could potentially be used clinically to assess the mechanical load of the LV and to monitor the peripheral hemodynamics such as blood flow pulsatility and risk of intestinal bleeding.

While the existence of structural adaptation of coronary anastomoses is undisputed, the potential of coronary collaterals to be capable of functional adaptation has been questioned. For many years, collateral vessels were thought to be rigid tubes allowing only limited blood flow governed by the pressure gradient across them. This concept was consistent with the notion that although collaterals could provide adequate blood flow to maintain resting levels, they would be unable to increase blood flow sufficiently in situations of increased myocardial oxygen demand. However, more recent studies have demonstrated the capability of the collateral circulation to deliver sufficient blood flow even during exertion or pharmacologic stress. Moreover, it has been shown that increases in collateral flow could be attributed directly to collateral vasomotion. This review summarizes the pathophysiology of the coronary collateral circulation, ie the functional adapation of coronary collaterals to acute alterations in the coronary circulation.

Background Ischemia monitoring cannot always be performed by 12-lead ECG. Hence, the individual performance of the ECG leads is crucial. No experimental data on the ECG's specificity for transient ischemia exist. Methods In 45 patients a 19-lead ECG was registered during a 1-minute balloon occlusion of a coronary artery (left anterior descending artery [LAD], right coronary artery [RCA] or left circumflex artery [LCX]). ST-segment shifts and sensitivity/specificity of the leads were measured. Results During LAD occlusion, V3 showed maximal ST-segment elevation (0.26 mV [IQR 0.16–0.33 mV], p = 0.001) and sensitivity/specificity (88% and 80%). During RCA occlusion, III showed maximal ST-elevation (0.2 mV [IQR 0.09–0.26 mV], p = 0.004), aVF had the best sensitivity/specificity (85% and 68%). During LCX occlusion, V6 showed maximal ST-segment elevation (0.04 mV [IQR 0.02–0.14 mV], p = 0.005), and sensitivity/specificity was (31%/92%) but could be improved (63%/72%) using an optimized cut-off for ischemia. Conclusion V3, aVF and V6 show the best performance to detect transient ischemia.

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.

AIM To compare functional assessment of coronary stenosis severity by fractional flow reserve (FFR) measurement as induced by systemic adenosine and by regional reactive myocardial hyperemia. METHODS AND RESULTS The primary study endpoints were coronary pressure-derived FFR values in response to intravenous adenosine infusion (140µg/min/kg) and to a 1-minute proximal coronary artery balloon occlusion (reactive hyperemia) for the same stenosis of interest. The secondary study endpoint was coronary collateral flow index (CFI) during the same occlusion. CFI is the ratio between simultaneous mean arterial occlusive pressure and mean aortic pressure both subtracted by central venous pressure. As a reference, coronary artery stenoses were assessed quantitatively as percent diameter reduction (%S). Hundred-and-twentyfive patients with coronary artery disease were included in the study. There was an inverse association between quantitatively determined structural stenosis severity and adenosine-induced FFR as well as post-ischemic reactive hyperemia FFR (%S=1-0.004FFR; both at p

Background— The objective of this study is to test the effect of permanent right internal mammary artery device closure on coronary collateral function and myocardial ischemia. Methods and Results— This was a prospective, open-label clinical trial in 50 patients with coronary artery disease. The primary study end point was coronary collateral flow index as obtained during a 1-minute proximal right coronary artery (RCA) and left coronary artery balloon occlusion at baseline before and at follow-up examination 6 weeks after distal right internal mammary artery device closure. Collateral flow index is the ratio between simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure, both subtracted by central venous pressure. Secondary study end points were fractional flow reserve during vessel patency, the quantitative intracoronary ECG ST-segment elevation, and angina pectoris during the same 1-minute coronary occlusion. Collateral flow index in the untreated RCA and left coronary artery changed from 0.071±0.082 at baseline to 0.132±0.117 ( P P =0.29), respectively. RCA fractional flow reserve increased significantly ( P =0.0029) from baseline to follow-up examination, despite deferral of coronary intervention in all patients. There was a decrease in intracoronary ECG ST-elevation during RCA occlusion from baseline to follow-up examination ( P =0.0015); it did not change in the left coronary artery. Angina pectoris during RCA occlusion tended to occur in fewer patients at follow-up versus baseline examination ( P =0.06). Conclusions— Permanent right internal mammary artery device closure seems to augment extracardiac ipsilateral coronary supply to the effect of reducing ischemia in the dependent myocardial region. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02475408.

PurposeTo address the need for dialogue between librarians, teachers and scholars in research institutions, as the information environment becomes increasingly complex.Design/methodology/approachA discussion of the impact of technology, budgets and collection storage practices on library users and their research patterns; examination of the methodologies for assessing that impact and continuing to meet user needs in a changing environment.FindingsDespite trends toward shared collections and a library of access rather than ownership, it is still necessary to develop careful knowledge of one's patrons and to shape one's collections and services to meet local needs.Practical implicationsLibraries must aggressively use focus groups, surveys and above all the personal relationship between faculty and library subject specialists to shape the development and management of their collections and the services they offer. These methods must shape not only one's title‐by‐title selection but one's larger, policy decisions and the overall configuration of one's collections.Originality/valueA broad assessment of the relationship between the new information landscape and the manner in which librarians and users communicate.

A 45-year-old sedentary office worker (187 cm, 117 kg, body mass index 34) gradually developed intolerance to physical exercise and suffered from general fatigue. He bought an electric bicycle to commute to work and covered a total distance of 80 km per day five times a week. In the next months, …

Background: There is limited information on the prognostic impact of the collateral circulation in patients with coronary artery disease (CAD). Apart from the lack of data on the relation between collaterals and survival, this is due to the complete unawareness of whether such an association would be causal. Methods and results: 1'181 patients with stable CAD followed-up between March 1996 and April 2011 underwent a total of 1'771 quantitative, coronary pressure-derived collateral flow index (CFI) measurements. 152 patients had been included in randomized trials on the longitudinal effect of different arteriogenic protocols on CFI. The entire study population was prospectively included in a CFI data base containing information on collateral function parameters obtained during a 1-minute coronary balloon occlusion. CFI was calculated as the ratio between mean distal coronary occlusive pressure and mean aortic pressure both subtracted by central venous pressure. Follow-up information on the occurrence of all-cause mortality and major adverse cardiac events after study inclusion was collected. Cumulative 15-year survival rate in relation to all-cause deaths was 48% in patients with CFI

Background— Despite the fact that numerous studies have pursued the strategy of improving collateral function in patients with peripheral artery disease, there is currently no method available to quantify collateral arterial function of the lower limb. Methods and Results— Pressure-derived collateral flow index (CFIp, calculated as (occlusive pressure−central venous pressure)/(aortic pressure−central venous pressure); pressure values in mm Hg) of the left superficial femoral artery was obtained in patients undergoing elective coronary angiography using a combined pressure/Doppler wire (n=30). Distal occlusive pressure and toe oxygen saturation (Sa o 2 ) were measured for 5 minutes under resting conditions, followed by an exercise protocol (repetitive plantar-flexion movements in supine position; n=28). In all patients, balloon occlusion of the superficial femoral artery over 5 minutes was painless under resting conditions. CFIp increased during the first 3 minutes from 0.451±0.168 to 0.551±0.172 ( P =0.0003), whereas Sa o 2 decreased from 98±2% to 93±7% ( P =0.004). Maximal changes of Sa o 2 were inversely related to maximal CFIp ( r 2 =0.33, P =0.003). During exercise, CFIp declined within 1 minute from 0.560±0.178 to 0.393±0.168 ( P o 2 declined to a minimum of 86±6% ( P =0.002). Twenty-five patients (89%) experienced pain or cramps/tired muscles, whereas 3 (11%) remained symptom-free for an occlusion time of 10 minutes. CFIp values were positively related to the pain-free time span ( r 2 =0.50, P =0.002). Conclusions— Quantitatively assessed collateral arterial function at rest determined in the nonstenotic superficial femoral artery is sufficient to prevent ischemic symptoms during a total occlusion of 5 minutes. During exercise, there is a decline in CFIp that indicates a supply-demand mismatch via collaterals or, alternatively, a steal phenomenon. Clinical Trial Registration—URL: http://www.clinicaltrials.gov . Unique identifier: NCT01742455.

Coronary collaterals are an alternative source of blood supply to myocardium jeopardized by ischaemia. In comparison with other species, the human coronary collateral circulation is very well developed. Among individuals without coronary artery disease (CAD), there are preformed collateral arteries preventing myocardial ischaemia during a brief vascular occlusion in 20-25%. Determinants of such anastomoses are low heart rate and the absence of systemic arterial hypertension. In patients with CAD, collateral arteries preventing myocardial ischaemia during a brief occlusion are present in every third individual. Collateral flow sufficient to prevent myocardial ischaemia during coronary occlusion amounts to one-fifth to one-fourth the normal flow through the open vessel. Myocardial infarct size, the most important prognostic determinant after such an event, is the product of coronary artery occlusion time, area at risk for infarction, and the inverse of collateral supply. Well-developed coronary collateral arteries in patients with CAD mitigate myocardial infarcts and improve survival. Approximately one-fifth of patients with CAD cannot be revascularized by percutaneous coronary intervention or coronary artery bypass grafting. Therapeutic promotion of collateral growth is a valuable treatment strategy in those patients. It should aim at growth of large conductive collateral arteries (arteriogenesis). Potential arteriogenic approaches include the treatment with granulocyte colony-stimulating factor, physical exercise training, and external counterpulsation.

OBJECTIVE This study tested the hypothesis that global physical activity and physical performance parameters are directly related to invasively obtained left superficial femoral artery (SFA) collateral flow index (CFI). BACKGROUND So far, the association between different measures of physical exercise activity and quantitative lower limb collateral function has not been investigated. METHODS The primary study end point was pressure-derived CFI as obtained during a 3 min left SFA balloon occlusion. CFI is the ratio of simultaneously recorded mean SFA distal occlusive pressure divided by mean aortic pressure, both subtracted by central venous pressure. As independent variables, the items of the Global Physical Activity Questionnaire (GPAQ) and physical exercise performance (maximal workload in watts) as achieved during a bicycle or treadmill exercise test were determined. The secondary study end point was transcutaneous left calf partial oxygen pressure (PO2 in mm Hg) divided by transcutaneous PO2 at a non-ischaemic reference site as obtained simultaneously to CFI measurement. RESULTS Of the 110 study patients undergoing diagnostic coronary angiography, 79 belonged to the group without and 31 with engagement in regular intensive leisure time physical activity according to GPAQ. Left SFA CFI tended to be lower in the group without than with intensive leisure time physical activity: 0.514 ±0.141 vs 0.560 ±0.184 (p =0.0566). Transcutaneous PO2 index was associated with simultaneous left SFA CFI: CFI =018 +0.57 PO2 index; p

Background: In the absence of beta-blockers, a low heart rate is known to be related to improved coronary collateral function. So far, the effect of heart rate reduction by ivabradine in patients with chronic stable coronary artery disease (CAD) on coronary collateral function has not been investigated. Methods and results: This was a prospective study in 43 patients with chronic stable CAD who were randomly allocated to placebo or ivabradine given for the duration of 6 months. The primary study endpoint was collateral flow index (CFI) as obtained during a 1-minute coronary artery balloon occlusion at study inclusion (baseline) and at the 6-month follow-up examination. CFI was calculated as the ratio between simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. During follow-up, heart rate changed by +0.2±7.8 beats/min in the placebo group and by -7.7±11.7 beats/min in the ivabradine group (p=0.0143; left panel). In the placebo group, CFI decreased from 0.140±0.095 at baseline to 0.109±0.068 at follow-up (p=0.12); it increased from 0.118±0.089 at baseline to 0.152±0.092 at follow-up in the ivabradine group (p=0.08). 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 +0.038±0.095 in the ivabradine group (p=0.0179; right panel). ![Figure][1] Delta heart rate and delta CFI Conclusions: Heart rate reduction by ivabradine appears to have a positive effect on coronary collateral function in patients with chronic stable CAD. [1]: pending:yes