Electrochemical Beacon Method to Quantify 10 Attomolar Nucleic Acids with a Semilog Dynamic Range of 7 Orders of Magnitude.

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.

Effect of permanent right internal mammary artery occlusion on right coronary artery supply: A randomized placebo-controlled clinical trial.

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 ±â€¯0.068 in the verum group and -0.021 ±â€¯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.

Crystallization at droplet interfaces for the fabrication of geometrically programmed synthetic magnetosomes.

Biological systems demonstrate exquisite three dimensional (3D) control over crystal nucleation and growth using soft micro/nanoenvironments, such as vesicles, for reagent transport and confinement. It remains challenging to mimic such biomineralization processes using synthetic systems. A synthetic mineralization strategy applicable to the synthesis of artificial magnetosomes with programmable magnetic domains is described. This strategy relies on the compartmentalization of precursors in surfactant-stabilized liquid microdroplets which, when contacted, spontaneously form lipid bilayers that support reagent transport and interface-confined magnetite nucleation and growth. The resulting magnetic domains are polarized and thus readily manipulated using magnetic fields or assembled using droplet-droplet interactions. This strategy presents a new, liquid phase procedure for the synthesis of vesicles with geometrically controlled inorganic features that would be difficult to produce otherwise. The artificial magnetosomes demonstrated could find use in, for example, drug/cargo delivery, droplet microfluidics, and formulation science.

The effect of pegylated granulocyte colony-stimulating factor on collateral function and myocardial ischaemia in chronic coronary artery disease: A randomized controlled trial.

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.

Function of natural internal mammary-to-coronary artery bypasses and its effect on myocardial ischemia.

BACKGROUND: The function of naturally existing internal mammary (IMA)-to-coronary artery bypasses and their quantitative effect on myocardial ischemia are unknown. METHODS AND RESULTS: The primary end point of this study was collateral flow index (CFI) obtained during two 1-minute coronary artery balloon occlusions, the first with and the second without simultaneous distal IMA occlusion. The secondary study end point was the quantitatively determined intracoronary ECG ST-segment elevation. CFI is the ratio of simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. A total of 180 pairs of CFI measurements were performed among 120 patients. With and without IMA occlusion, CFI was 0.110±0.074 and 0.096±0.072, respectively (P<0.0001). The difference of CFI obtained in the presence minus CFI obtained in the absence of IMA occlusion was highest and most consistently positive during left IMA with left anterior descending artery occlusion and during right IMA with right coronary artery occlusion (ipsilateral occlusions): 0.033±0.044 and 0.025±0.027, respectively. This CFI difference was absent during right IMA with left anterior descending artery occlusion and during left IMA with right coronary artery occlusion (contralateral occlusions): -0.007±0.034 and 0.001±0.023, respectively (P=0.0002 versus ipsilateral occlusions). The respective CFI differences during either IMA with left circumflex artery occlusion were inconsistently positive. Intracoronary ECG ST-segment elevations were significantly reduced during ipsilateral IMA occlusions but not during contralateral or left circumflex artery occlusions. CONCLUSION: There is a functional, ischemia-reducing extracardiac coronary artery supply via ipsilateral but not via contralateral natural IMA bypasses. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCTO1676207.

Direct quantitative assessment of the peripheral artery collateral circulation in patients undergoing angiography.

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 (Sao2) 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 Sao2 decreased from 98±2% to 93±7% (P=0.004). Maximal changes of Sao2 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<0.0001) and reached its minimum after 2 minutes of exercise (0.347±0.176), whereas Sao2 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.

Effects of Thoratec pulsatile ventricular assist device timing on the abdominal aortic wave intensity pattern.

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.

Electrocardiographic ST-segment monitoring during controlled occlusion of coronary arteries.

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 (0.26mV [IQR 0.16-0.33mV], p=0.001) and sensitivity/specificity (88% and 80%). During RCA occlusion, III showed maximal ST-elevation (0.2mV [IQR 0.09-0.26mV], p=0.004), aVF had the best sensitivity/specificity (85% and 68%). During LCX occlusion, V6 showed maximal ST-segment elevation (0.04mV [IQR 0.02-0.14mV], 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.

The human coronary collateral circulation: development and clinical importance.

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.

Early Switch From Intravenous to Oral Antibiotics in Skin and Soft Tissue Infections: An Algorithm-Based Prospective Multicenter Pilot Trial.

Background: In hospitalized patients with skin and soft tissue infections (SSTIs), intravenous (IV) empiric antibiotic treatment is initiated. The best time point for switching from IV to oral treatment is unknown. We used an algorithm-based decision tree for the switch from IV to oral antibiotics within 48 hours and aimed to investigate the treatment outcome of this concept. Methods: In a nonrandomized trial, we prospectively enrolled 128 patients hospitalized with SSTI from July 2019 to May 2021 at 3 institutions. Clinical and biochemical response data during the first week and at follow-up after 30 days were analyzed. Patients fulfilling criteria for the switch from IV to oral antibiotics were assigned to the intervention group. The primary outcome was a composite definition consisting of the proportion of patients with clinical failure or death of any cause. Results: Ninety-seven (75.8%) patients were assigned to the intervention group. All of them showed signs of clinical improvement (ie, absence of fever or reduction of pain) within 48 hours of IV treatment, irrespective of erythema finding or biochemical response. The median total antibiotic treatment duration was 11 (interquartile range [IQR], 9-13) days in the invention group and 15 (IQR, 11-24) days in the nonintervention group (P < .001). The median duration of hospitalization was 5 (IQR, 4-6) days in the intervention group and 8 (IQR, 6-12) days in the nonintervention group (P < .001). There were 5 (5.2%) failures in the intervention group and 1 (3.2%) in the nonintervention group after a median follow-up of 37 days. Conclusions: In this pilot trial, the proposed decision algorithm for early switch from IV to oral antibiotics for SSTI treatment was successful in 95% of cases. Clinical Trials Registration. ISRCTN15245496.

Extracardiac coronary steal induced by upper limb hyperemia: a feature of internal mammary artery arteriogenesis.

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 beneficial functional connection is invertible and can be linked to coronary steal, the verification of whose hypothesis would provide alternate proof to the mentioned functional evidence. This was an observational study including 40 patients with chronic coronary syndrome, distal IMA occlusion, and upper limb hyperemia (verum group), and 40 propensity score matched controls (placebo group) without IMA occlusion or hyperemia. Primary study end point was the intergroup difference and temporal development in coronary collateral function (i.e., collateral flow index; CFI) as obtained at 30, 45, and 60 s 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-min suprasystolic inflation ipsilateral to the sensor-wired coronary artery with release immediately after the first CFI measurement. Between the first and the second CFI measurement, CFI change (i.e., CFI@45s - CFI@30s) was absent in the verum group whereas there was CFI recruitment in the placebo group: 0.000 ± 0.023 and +0.009 ± 0.013, respectively; P = 0.032. Among patients with artificial distal 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.NEW & NOTEWORTHY Induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal among patients with artificial distal internal mammary artery occlusion. Coronary steal via the occluded internal mammary arteries serves as alternate proof of concept of the already existing evidence of their functional extracoronary collateral supply.

Functional assessment of myocardial ischaemia by intracoronary ECG.

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<0.0001). There were inverse linear correlations between FFR and %S: FFR=1.1-6.1*10-3*%S (r2=0.494; p<0.0001), and between iFR and %S: iFR=1.27-8.6*10-3*%S (r2=0.461; p<0.0001). Using a %S-threshold of ≥50% as the reference for structural stenosis relevance, receiver operating characteristics-analysis of absolute icECG ST-segment shift during hyperemia showed an area under the curve (AUC) of 0.678±0.054 (p=0.002; sensitivity=85%, specificity=50% at 0.34 mV). AUC for FFR was 0.854±0.037 (p<0.0001; sensitivity=64%, specificity=96% at 0.78), and for iFR it was 0.816±0.043 (p<0.0001;sensitivity=62%, specificity=96% at 0.83). CONCLUSIONS: Hyperaemic icECG ST-segment shift detects structurally relevant coronary stenotic lesions with high sensitivity, while they are identified highly specific by FFR and iFR.

Effect of acute myocardial ischemia on inferolateral early repolarization.

BACKGROUND: Inferolateral early repolarization (ER) is associated with an increase in arrhythmic risk, particularly in the presence of myocardial ischemia. OBJECTIVE: The purpose of this study was to determine the effect of myocardial ischemia on ER. METHODS: We retrospectively analyzed procedural electrocardiograms (ECGs) of patients with ER undergoing a controlled, 1-minute coronary balloon occlusion for collateral function testing. ECG leads with ER were analyzed immediately before coronary balloon occlusion (PRE), at 60 seconds of coronary balloon occlusion (OCCL), and >30 seconds after balloon deflation. RESULTS: Seventy-seven patients with ER in the preprocedural 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 cases (44%) from 0.00 ± 0.03 to 0.05 ± 0.06 mV (P < .0001). In this group, J-wave amplitude (JWA) increased from 0.10 ± 0.07 to 0.13 ± 0.09 mV (P < .0001). ST in the ER lead decreased or was unchanged in 121 cases (56%) from PRE to OCCL (from 0.01 ± 0.05 to -0.02 ± 0.04 mV; P < .0001). In this group, JWA decreased from 0.10 ± 0.05 to 0.08 ± 0.07 mV (P < .0001). The change in JWA was related to the change in ST (linear regression analysis; R2 = 0.34; P < .0001), while there was no relation between the change in R-wave amplitude and the change in ST (R2 = 0.0003; P = .83). CONCLUSION: During acute ischemia, JWA mirrors ST-segment changes. This may explain increased arrhythmic vulnerability of patients with ER during myocardial ischemia. It also adds weight to the hypothesis of ER being a phenomenon of repolarization.

Mechanically Induced Hydrophobic Recovery of Poly(dimethylsiloxane) (PDMS) for the Generation of Surfaces with Patterned Wettability.

Silicone elastomers are used in a variety of "stretchable" technologies (e.g., wearable electronics and soft robotics) that require the elastomeric components to accommodate varying magnitudes of mechanical stress during operation; however, there is limited understanding of how mechanical stress influences the surface chemistry of these elastomeric components despite the potential importance of this property with regards to overall function. In this study, plasma-oxidized silicone (poly(dimethylsiloxane)) films were systematically subjected to various amounts of tensile stress and the resulting surface chemical changes were monitored using contact angle measurements, X-ray photoelectron spectroscopy, and gas chromatography-mass spectrometry. Understanding the influence of mechanical stress on these materials made possible the development of a facile method for the rapid, on-demand switching of surface wettability and the generation of surface wettability patterns and gradients. The use of mechanical stress to control surface wettability is broadly applicable to the fields of microfluidics, soft robotics, printing, and to the design of adaptable materials and sensors.

Electrocardiographic predictors of mortality in patients after percutaneous coronary interventions - a nested case-control study.

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.

Invasive Assessment of the Human Arterial Palmar Arch and Forearm Collateral Function During Transradial Access.

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 (CFIrad) 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. CFIrad 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 CFIrad and MAT in seconds (s): MAT=64-63×CFIrad ( r2=0.229; P<0.0001). Two hundred eleven patients had a normal and 39 patients an abnormal (>15 seconds) MAT. The group with normal MAT had a CFIrad of 0.830±0.111, and patients with abnormal MAT had a CFIrad of 0.648±0.224 ( P<0.0001). 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.

Left ventricular afterload reduction by transcatheter aortic valve implantation in severe aortic stenosis and its prompt effects on comprehensive coronary haemodynamics.

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.

Effect of Permanent Right Internal Mammary Artery Closure on Coronary Collateral Function and Myocardial Ischemia.

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<0.0001) at follow-up examination and from 0.106±0.092 to 0.081±0.079 (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.

Reactive myocardial hyperaemia for functional assessment of coronary stenosis severity.

AIMS: Our aim was to compare functional assessment of coronary stenosis severity by fractional flow reserve (FFR) measurement, as induced by systemic adenosine, and by regional reactive myocardial hyperaemia. METHODS AND RESULTS: The primary study endpoints were coronary pressure-derived FFR values in response to intravenous adenosine infusion (140 µg/min/kg), and to a one-minute proximal coronary artery balloon occlusion (reactive hyperaemia) 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). One hundred and twenty-five 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-ischaemic reactive hyperaemia FFR (%S=1-0.004 FFR; both at p<0.0001). Sensitivity and specificity for detecting a stenosis of ≥50% at an FFR threshold of 0.80 was 0.891 and 0.605 (adenosine-induced FFR), and 0.817 and 0.684 (post-ischaemic FFR), respectively. The FFR difference for a given stenosis (post-ischaemic minus adenosine-induced FFR) was directly related to CFI. CONCLUSIONS: Regional reactive hyperaemia FFR is not inferior to systemic adenosine FFR in detecting structurally relevant coronary stenosis. Depending on the absence or presence of functional collaterals, systemic adenosine-induced FFR may underestimate or overestimate stenosis severity, respectively.