The Wave Free Carl W. Lucas Online Now Thriller genres

19 de febrero de 2020 - 09:15

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Publisher: Joe Goldberg
Info: #EPNupe Two types of pain we all go through. Pain of discipline or the pain of regret. I like kickboxing and chicken wings

Countries=USA

Katia Winter

Duration=1 h, 30 Minute

tomatometer=6,9 / 10 Star

Genre=Sci-Fi, Thriller

Wow. 7:30. I'm quite happy to go on

Are you sure you want to delete this collection? You have reached your max collections allowed. Select the collections you wish to keep using. All other collections will be locked until you upgrade to a Premium subscription. Get unlimited collections and +2, 504, 500 icons or Choose your 3 favourite collections. Base 64 encoded image HTML image CSS background Copy the base64 encoded data and insert it in your document. Need help? Maybe this link can help you;) Edit icons Grid: This icon replaces the current icon A new icon will be created in your collection. Select a color Replace with Last selected colors You have not selected any color yet Original icon colors Download: Choose a format Select a size (in pixels). Was it easy to find this icon? Tell us how we could improve Do you find the related icons we show you at the bottom useful? Download options Collection: Pack: Introducing collections Collections are the core of our web app. Do you want to know how to use them? Press next to watch the guide. 1 of 9 Collections list This is a list of your collections. You can change their names and they are sorted by use. Click on one of them to start using it. 2 of 9 Create a collection Click on this button to create a collection. 3 of 9 Change name Click here to change the name of the collection 4 of 9 Active collection This is your active collection. One collection can have up to 256 icons if you are a registered user or 50 if you are not registered. 5 of 9 Color Add color to all the icons in your collection. 6 of 9 Edit mode Enter the edit mode by clicking the pencil icon to edit the name and color of each icon separately. 7 of 9 Delete Have you finished with this collection? Delete it and create a new one here. 8 of 9 Enjoy! And that is all, if you have any question you can contact our support team here. Thank you for using Flaticon, we hope you enjoy our service 9 of 9.

Tsunami- WHY ARE U RUNNING WHY ARE U RUNNING! PEOPLE- AHHHHHHHHH. The complete guide to cash flow for small businesses This guide covers the ins and outs of cash flow to help you build a financial plan to keep capital circulating through your business. more Empower yourself with our Fearless Accounting Guide Accounting doesn’t have to be scary. Our guide has pages of easy-to-follow tips and lessons to help you run your business with confidence. The complete guide to getting paid This guide will teach you how to set prices, send professional invoices, accept payments, and protect yourself from unpaid invoices and payment scams. more.

Falafel inc. Guys, don't be silly. it's herbie driving. Just Love : D. Falador massacre runescape. Fala portugal. I think Michael Winterbottom is looking to rival Armando Ianucci as far as script is concerned. Falang translation system. If you do another one, do hibana pls that pv is 😳. Fala chen. Faladdin. Menschen die aus Geschichte lernen... sowas gibts wohl auch nur in Literatur und nicht in der Realität. Why Eva Green always suffers so much in movies and tv shows? God damn, I just want to see her happy. Fala meaning. I feel ashamed that I once was so childish that I hated these wonderful girls because of Naeun's WGM. I want to apologise to Pink Pandas and Apink. Please forgive me, I hope you feel my sincere apologies.

Integrating brain waves so we absorb, retain and recall information better helps us succeed. Here are details about brain waves from a Scientific American article “What is the Function of the Brainwaves? ” (1) by Ned Herrmann an educator who has developed models of brain activity and integrated them into teaching and management training. Herrmann headed management education at General Electric, where he developed many of his ideas. Here is his explanation. It is well known that the brain is an electrochemical organ; researchers have speculated that a fully functioning brain can generate as much as 10 watts of electrical power. Other more conservative investigators calculate that if all 10 billion interconnected nerve cells discharged at one time that a single electrode placed on the human scalp would record something like five millionths to 50 millionths of a volt. There are four categories of these brainwaves, ranging from the most activity to the least activity. When the brain is aroused and actively engaged in mental activities, it generates beta waves. The next brainwave category in order of frequency is alpha. A person who has completed a task and sits down to rest is often in an alpha state. A person who takes time out to reflect or meditate is usually in an alpha state. A person who takes a break from a conference and walks in the garden is often in an alpha state. The next state, theta brainwaves, are typically of even greater amplitude and slower frequency. A person who has taken time off from a task and begins to daydream is often in a theta brainwave state. Individuals who do a lot of freeway driving often get good ideas during those periods when they are in theta and discovers that they can’t recall the last five miles–induced by the process of freeway driving. The repetitious nature of that form of driving compared to a country road would differentiate a theta state and a beta state in order to perform the driving task safely. It is a state where tasks become so automatic that you can mentally disengage from them. The ideation that can take place during the theta state is often free flow and occurs without censorship or guilt. It is typically a very positive mental state. When we allow the different waves to interconnect freely we gain unimaginable intellect. Our mental and physical being improve. This is why I believe our “Super Spanish” course works is the most important we conduct. This course is based on the power of silence and music. This course is based on the fact that silence and music supercharge and connect your mind, body and soul. The knowledge and experience gained in that course about silence, smart music and super nutrition allows delegates to enhance productivity and creativity. The concepts gained show delegates how to create their own program of greater wisdom and help them build new skills at work in study and play. One benefit is that delegates gain tools to quickly become fluent in Spanish…yet as this former delegate wrote, they learn much more. “Hi Gary & Merri, You two are the BEST!!! Your seminar was fantastic! I am so excited. I had procrastinated fulfilling my continuing education for my Broker’s License and then just before my surgeries, I realized my expiration date isn’t Nov. 12th – it is Sept 12th. Well, as you can see prior to taking your course I had only completed 3 units of the required 45 units. I thought I would take your course and then complete my remaining 42 units over the next 2 weeks. However, I took one class exam on Saturday night, August 27th. I didn’t even take the cellophane off the required Course manuals until after I saw the two of you today less than 5 hours ago! I used your techniques and completed 39 units of continuing education today. I have now completed all 45 units. All of my test scores were in the 90. 6-96% range. My course exam information is listed below. I just wanted to let you know how valuable your course was to me. Thanks again! ” Suzy Kurinsky Gary (1) What is the Function of Brain Waves Learn Spanish in Three Days ONLINE The “Learn Spanish in Three Day Course” is available online. Learn Spanish in a day, or a week, month or any time frame that works for you. I’m Gary Scott. Over fifty years ago I started a business that has helped hundreds of thousands of subscribers learn about investing in Hong Kong (1960s and 1970s), Switzerland, London, Isle of Man (1970s and 1980s) and across Europe. In the 1990s we took investors to Panama, Mexico and Ecuador. That’s when we realized an incredible need for an easy way to learn Spanish. See below how my wife Merri was able to create a program that allowed students to be speaking and understanding Spanish in just three days. Thousands of subscribers have learned Spanish at our three day Super Spanish course. These courses have been taught across the US, in Canada, Panama, Mexico, Ecuador, Uruguay and Spain. A Super Spanish course in Florida. Read below to see how and why we are now offering our Super Spanish course ONLINE for the first time. Speaking Spanish as a second language has huge benefits. You can become one of the rare North Americans who can get along in Spanish speaking countries. You can be one of the special people who can communicate with 10 million non-English speakers in the USA. Spanish is the second most used language in the USA. There are more Spanish speakers than speakers of Chinese, French, German, Italian, Hawaiian, and the Native American languages combined. According to the Census Bureau, Spanish is the primary language of nearly 50 million people in the US. This is the largest Spanish-speaking community outside of Mexico. Only half of these speakers also speak English “very well, ” and 19% do not speak English at all. You become one of a leading few when you speak Spanish. Yet there are more benefits. An article in England’s leading newspaper, the Telegraph, entitled “Why learn a foreign language? Benefits of bilingualism” (1) sum up the biggest benefit of learning a second language and increased intelligence. The article says (bolds are mine): “Learning a foreign language is more than just a boost to your CV or handy for traveling. It will make you smarter, more decisive and even better at English. Physiological studies have found that speaking two or more languages is a great asset to the cognitive process. The brains of bilingual people operate differently than single language speakers, and these differences offer several mental benefits. ” The article then explains studies that show seven cognitive advantages gained from learning a foreign language. #1: You become smarter #2: You build multitasking skills #3: You stave off Alzheimer’s and dementia #4: Your memory improves #5: You become more perceptive #6: Your decision-making skills improve #7: You improve your English Does it sound impossible to learn Spanish in three days? Yes, it is impossible when you try to learn Spanish in the old, traditional way. Y ou may choose to take more time using the ONLINE course to learn Spanish, but thousands of our readers have learned to speak Spanish in only three days at our Spanish courses. There is a scientific method of learning… proven and described in numerous best selling books that create educational jumps by making education natural, easy and fun. This course works because it is education without stress! A special method of learning (called Super Learning) was created and refined by the Bulgarian educational master, Georgi Lozanov. Lozanov transformed the entire Soviet educational system to such a degree that this third world country beat the USA into space. My wife Merri was lucky to be one of a handful of students outside of Bulgaria who were allowed to be taught this system in the early 1970s. She practiced this unique and remarkable form of education for four decades. It was a delight! Merri and I began integrating these techniques with other shamanic and educational tactics we had gained in our global travels and then applied them to teach Spanish in three days. The course has been proven again and again by the thousands who have used this system. You can read a few of the many raves we have received from students who have learned from the Super Thinking Spanish course we created. Here are a few quotes from delegates of the course. One delegate from St. Louis wrote: Hi Gary, Just ended forty-five years in dentistry last week, and I’m on to a new career. What is my new career? Still formulating, but the eye -opening, mind expanding Super-Spanish course last weekend in St. Louis surely shows me the opportunity exists to expand my horizons. Besides having a lot of nice people to learn our new language; the methods Merri and you developed proved to be just what you said they would be. We all and I in particular relaxed our way to new learning. I feel so very comfortable with the basis of my new language skills that I know I will be spitting out great Spanish sentences by the time I reach Ecuador in October. Last year I spent six weeks in Ecuador and now I plan on conversing with the people. Today’s excerpt of your newsletter really hit home. You do what you say you will. There are no surprises or hidden sales tricks. The only tricks are beneficial to our learning. Thank you for a wonderful experience that I was quite unable to grasp how you would pull it off. You did, however, and I look forward to other courses that you offer, and I have absolutely no doubt they also will work beneficially. Best regards, Denis Molloy. Another wrote about the Super Spanish course: Buenos Dias, here is a testimonial for Super Thinking-Super Spanish. Please feel free to use all or part in promotions for the course. In addition, you may give my email address to any prospect “on the fence” about enrolling. Yesterday, in Cotacachi, Ecuador, I finished Super Spanish. I had high expectations for the course and they were exceeded. After three days, I can speak Spanish in complete sentences. In simple conversations, such as buying groceries or ordering a meal, I can make myself understood. I think that’s incredible! Although I am far from the competence level of a native speaker, I feel I’ve taken a giant step forward in learning Spanish so that I can experience the people and culture of Ecuador. The foregoing benefits would have more than justified the time and money I invested in Super Spanish. And learning some Spanish was not the most important benefit I got from the course. Prior to leaving the USA, I had felt for some time that the pace of life there was unhealthy for me (and for most people) and I did nothing about it. I’ve thought about the pace issue during the course. One of the key elements Merri Scott designed into Super Spanish is placing the student in the optimal state for learning. In class, the past three days, I’ve been re-introduced to guided journeys and introduced to the calming effects of Baroque music (). What a blessing! I’m inclined to make one or both a daily part of my life. Rob Christi. Cotacachi, Ecuador Another attendee from a course wrote: “I took this incredible class a few weeks ago, and I would like to tell anyone that is interested, that it is an amazing three days of learning with lots of laughs included. You leave everyday wanting to learn more and are so excited to do so. “Other Spanish classes and tutoring made us feel like it would take forever to get to the point where we could put it into practice, but this method gave us a more fluent use for everyday life almost immediately AND the confidence to use it. It is a fantastic way to show people how much they know and give confidence to learn and use Spanish creating a momentum. “They made learning Spanish easy and fun in a very relaxed, comfortable atmosphere. I would definitely recommend this course. Even if you know some Spanish, this helps make it easier because of the less stress that no verb conjugations gives you. This gives you more confidence in yourself to try and speak it more. “The stress free atmosphere and tons of interaction and participation were very conducive to learning. The relaxation techniques alone are worth the price. The fact that I can now feel more comfortable conversing in Spanish with my new friends and neighbors is priceless. Muchas, muchas gracias. ” “I loved the relaxed environment. I picked up quite a lot of new vocabulary. I found this course very informative about how the language works, how I can make sentences and understand others better! Muchas Gracias! I had a call from Telcel (the local phone company) after our second class and I was able to speak and understand them for the first time. Despacio (meaning slowly) … a great word! Everyone should take this course before they pick up bad habits. ” “I liked how simply the course was organized and the positive attitude about learning. Thank you so much for helping me to learn Spanish! ” “I liked the laid back yet professional approach. I highly recommend this new, relaxing method of learning Spanish, I feel a lot more confident in the delivery of my words and sentences. It was taught in an excellent and very professional way. “It was a very enjoyable class. ” How The Course Works The first tactic is to use Baroque music to create Relaxed Concentration in the learning process. At least three best selling books, “Superlearning”, the “Mozart Effect” and “Superlearning 2000” have revealed insights about how to learn and think more powerfully based on systems drawn from the Bulgarian educational master, Dr. Georgi Lozanov. Merri was among just a few who learned directly from Lozanov. Super Spanish relaxed concentration session. You gain six valuable ONLINE Relaxed Concentration sessions in the online course that is delivered via the internet. The second tactic uses 17 unique lessons to provide Spanish fluency in a short time. Let me prove to you how this tactic works by teaching you hundreds of Spanish words in less than 30 seconds. Here is the proof. “Most words in English that end in ION are almost identical, just pronounced differently. For example action is accion, education-educacion, manipulation- manipulacion, etc. ” There you have it. How long did it take you to read the sentence? You now know hundreds of Spanish words that you will never forget. See examples of the words you already know below. How long would have taken you to memorize all those words? How soon would you have forgotten them? This is just one of seventeen Spanish lessons in the course. The next lesson teaches how to pronounce each of the nouns. Then, the third lesson teaches almost as many verbs, almost as quickly. The fourth lesson shows how to avoid conjugating verbs by sticking with the infinitive (far easier than it sounds). This simple lesson leaves a person sounding like a Spanish professor without ever conjugating a verb. Lesson five shows how to sound infinitely polite and yet get almost anything desired in Spanish. Lesson six gives valuable connectors and the seventh lesson triples the Spanish capacity with three words for “yesterday, ” “now” and “tomorrow”. By the end of three days you feel comfortable speaking Spanish. Plus the system is Impro-Dynamic. This means your Spanish keeps getting better even though you do not seem to be studying… practicing… or speaking Spanish. I was amazed by this as I traveled back and forth from the USA to Ecuador. The longer I was away from Ecuador… the better my Spanish became. My second language was automatically improving. The self improving feature comes because you learn to create Spanish sentences rather than remember them. The portion of the brain that creates is more powerful than the portion that recalls. When your mind creates something… it owns it! You do not have to remember. During the course you learn 4005 Spanish words that you already know. This eliminates the need to memorize 99% of Spanish words. You then learn how to create Spanish sentences from these words. Throughout the course you learn how to pronounce the sentences you create. When the course ends… the mind keeps working… and creating… so next time you begin to speak Spanish you’ll be surprised. You improve even though you have not actively worked on your lingual skill. Due to the difficulty of getting groups together to learn this valuable technique, we created an online program for subscribers to use the Super Spanish course at home. The normal three day course fee is $499 ($749 for a couple). The ONLINE course is available at the highly reduced price of $79. I’ll be in touch personally via email with each person who signs up for this course to see how it works or what is required to make it better. Once this test is complete, we plan to offer the program on a larger scale and at a much higher price. The ONLINE course has our, full satisfaction or money back, guarantee. Try Super Spanish for 60 days. If not fully satisfied, simply let us know for a full refund. Learn Spanish online $79 - using coupon code SPANISH70 at checkout to immediately save $70 off the regular price of $149. Here are more testimonials from previous Super Spanish Courses. Maggie wrote: It didn’t really seem possible that we would be speaking and understanding Spanish in only 3 days but the course made it happen in a very supportive learning environment. I would highly recommend this course for anyone wishing to learn “practical Spanish”. The teaching methods, use of relaxation, the use of native Spanish speakers for pronunciation and the teachers themselves who were approachable and helpful and always positive made this a very valuable class. This course improved my self confidence in my ability to learn and retain a language. It was presented with genuine enthusiasm, great energy and the style of learning is very effective. Gracias! It was a great experience. Nadine wrote: “Just spent the last 3 days in the most wonderful learning environment learning Spanish. What an amazing learning experience!! First day out of class and I could not stop thinking in Spanish WOW!! I am amazed by how much I learned, retained and how much more is showing up now that I am out of class. And the best part is THERE WAS NO STUDYING!! Indeed this is Super Thinking!!! I would highly recommend this to anyone that has ever had a desire to learn another language or learn anything in record time. And a few days after that …. As I went through my day, just hanging out with my son, I could see myself starting to think in Spanish. At first I thought it was amusing but as it continued and increased I thought “My goodness this is really remarkable amazing” It was really an effortless unfolding. I wasn’t at any point “trying” to think in Spanish, just words I knew would fly across the screen in my mind. And then this afternoon, my son cuddled up on the couch to watch some cartoons on his ipad and was watching Peppa Pig in Spanish…hmm coincidence? I think not, I’m radiating Spanish so much that my son is being influenced! Thanks a million again. This weekend the best learning experience of my life!! If you have ever had a desire to learn Spanish this is the way to do it! By the end of the first day I had more confidence and more practical ability than I had from any previous courses I had taken. It was fun and relaxed and full of laughter. You will leave this class excited to use what you have learned. Rather than leaving overwhelmed with how much you have yet to learn and master, you are equipped with the knowledge and know how to go out and communicate as well as the excitement to do it! ” Gary noted: “The whole approach is positive and conducive to learning at a level that benefits ALL participants. It is not intimidating and does not set up a pass/fail atmosphere. The presenters are terrific and the results unbelievable. It was relaxed, informal, friendly and effective. ” Twila said: “This class provided a very refreshing and relaxed way of learning. The atmosphere felt very safe to say the words you were practicing. I learned a lot in a way that will make it easy to apply. Starting with conversation is way more fun. How quickly you can learn! It was a great group, great instructors and great stories. The atmosphere in the classroom was so relaxed that learning Spanish felt like a breeze and not like a painful task. The relaxation exercises are really conducive to language learning. We learned A LOT in a short time and it was fun and the environment was non-threatening. ” Brigitte sent this: “Buenos Dias, Suzanne. su clase de espanol es excelente! Muchas Gracias!  I have already done what you suggested and went into the program listening to the music and going over the lessons. I know: Repetition……reinforcement…inking in the new language…’s all part of it. I loved your course and will certainly recommend it to friends. Who knows…. I might feel the urge and have the opportunity to repeat it at your beautiful place in Puerto Aventuras…. sabe? Hasta otro dia y saludos a su familia. ” Marie wrote: “I would highly recommend this course. The amount covered in 3 days is amazing! All with no stress. The correlation lessons and pronunciation practice has greatly reduced my anxiety to go out and use my Spanish. I really enjoyed the whole process and thank you for the take away tools. ” Learn Spanish online $79 - using coupon code SPANISH70 at checkout to immediately save $70 off the regular price of $149. Here is the English translation of a few of the many Spanish words you now know and will never forget. How long would it have taken you to memorize them? How soon would you forget? “Most words in English that end in ION are almost identical, just pronounced differently. For example, action is accion, education-educacion, manipulation- manipulacion, etc. ” Some more of these words: Combination, Attrition, Education, Vacation, Petition, Lotion, Motion, Construction, Abduction, Pronunciation, Concentration and a ton of others! Learn Young or Old Most Super Spanish students are all ages, Super Spanish students at this course ranged from nine to over eighty years old. Become a Spanish translator! The wife of one couple who attended explained how after just three days her husband ended up as an accidental translator. She wrote: Gary, I have sent Merri a couple of messages, and a story of Mike being able to translate yesterday for a Spanish person who couldn’t understand what a man was trying to tell him! Does it sound impossible to learn Spanish in three days? Yes, it is impossible when you try to learn Spanish in the old, traditional way. The video below shows a super fast way to gain the basics so you can communicate in Spanish in just three days. Click here for FREE Super Spanish video. Still can’t believe you can learn Spanish in a short time? You have nothing to lose but to try. The ONLINE Super Spanish course has our, full satisfaction or money back, guarantee. Try Super Spanish for 60 days. If not fully satisfied, simply let us know for a full refund. (1).

If its an Elijah wood movie than it wont be a shallow plot like dad just wants his liver or something. Falafel prague. Falafel recipes. This is literally the plot of like the 8th episode of supernatural. Like everything about it is just an extended version of that. Falalalala song. That thumbnail though... Fala hotel ft lauderdale. She was coming out of Marseilles harbor, and was standing out to sea rapidly, her sharp prow cleaving through the waves. "Oh, " cried Edmond, "to think that in half an hour I could join her, did I not fear being questioned, detected, and conveyed back to Marseilles! He rose on the waves, making signs of distress; but no one on board saw him, and the vessel stood on another tack. So she wasn't easily frightened, whatever happened, and when the wind began to howl and whistle, and the waves began to tumble and toss, our little girl didn't mind the uproar the least bit. Around and over it whirled, this way and that, and a few moments later the chicken-coop dropped far away into the sea, where the big waves caught it and slid it up-hill to a foaming crest and then down-hill into a deep valley, as if it were nothing more than a plaything to keep them amused. As he wandered up and down on the banks of the mill-pond he heard a rustling in the water, and when he looked near he saw a white woman rising up from the waves. He had hardly dipped them in the pond when the nixy rose up in the water, and seizing him in her wet arms she dragged him down with her under the waves. Bend thy fair head over the waves, thou lovelier than the ghost of the hills, when it moves, in a sunbeam at noon, over the silence of Morven. He took the wand with which he seals men's eyes in sleep or wakes them just as he pleases, and flew holding it in his hand over Pieria; then he swooped down through the firmament till he reached the level of the sea, whose waves he skimmed like a cormorant that flies fishing every hole and corner of the ocean, and drenching its thick plumage in the spray. On came the fairy boat, till it reached a moss-grown rock; and here it stopped, while the Fairies rested beneath the violet-leaves, and sang with the dancing waves. Once I shipped a sea so heavy that I had to stop and bail, with my heart fluttering like a bird, but gradually I got into the way of the thing and guided my coracle among the waves, with only now and then a blow upon her bows and a dash of foam in my face. Besides, our vessel only mounted to the surface of the waves at night to renew its stock of air; it was steered entirely by the compass and the log. De Guiche, who had been looking among the different boats for one stronger than the others, which might offer a chance of reaching the English vessels, perceiving the pilot-boat getting ready to start, said to Raoul: "Do you not think, Raoul, that intelligent and vigorous men, as we are, ought to be ashamed to retreat before the brute strength of wind and waves? " The modern ship is not the sport of the waves. Let us say that each of her voyages is a triumphant progress; and yet it is a question whether it is not a more subtle and more human triumph to be the sport of the waves and yet survive, achieving your end. On the Lei rose flames, the Fairy stood above, at that time, and beckoned with her right hand clearly and urgently to the infatuated Knight, while with a staff in her left hand she called the waves to her service. The fisherman used to go out all day long a-fishing; and one day, as he sat on the shore with his rod, looking at the sparkling waves and watching his line, all on a sudden his float was dragged away deep into the water: and in drawing it up he pulled out a great fish.

Lalala song. I've loved Ingrid since I was 5 and I'm 13 😂 She's just sooooooooooo amazing and unique, love her ❤️❤️❤️❤️. Falacia. I watched one marshmallow experiment video and one child found a way to eat the inside but leave the outside to try and trick the people running the experiment. I get such an energy rush when i hear this. Awsome.

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Fala hotel fort lauderdale. Falabella. Without~Registering~The~Wave Watch The Wave Online HBO 2018 Online Streaming Free Without Sign Up The Wave... Something went wrong, but don’t fret — let’s give it another shot. Instantaneous wave-free ratio Synonyms Instant flow reserve Purpose ascertain if individual has a stenosis The instantaneous wave-free ratio ( iFR, sometimes referred to as the instant wave-free ratio or instant flow reserve) is a diagnostic tool used to assess whether a stenosis is causing a limitation of blood flow in coronary arteries with subsequent ischemia. iFR is performed during cardiac catheterisation ( angiography) using invasive coronary pressure wires which are placed in the coronary arteries that are to be assessed. Pressure wires are commonly used by interventional cardiologists to guide decisions to perform revascularization, either by stenting or bypass surgery. Assessment of coronary stenoses [ edit] Coronary artery blockages or stenoses that limit blood flow to the heart muscle can cause angina and can be treated by stenting or bypass surgery. Relief of a stenosis by stenting aims to restore vessel patency with improvement in blood flow leading to a reduction in angina symptoms. However, if stenoses are not flow limiting, then they can be safely left alone without stenting or surgery and this help reduce patient's exposure to unnecessary procedures and potential complications. Identifying stenoses that cause flow limitation, or ischaemia, can be done in a variety of ways. Non-invasive tests can include stress testing such as exercise electrocardiograms, stress echocardiography, or perfusion imaging tests such as scintigraphy or SPECT. Alternatively, invasive tests can be performed at the time of angiography, and these include those that measure coronary flow velocity in the vessel, CFR or index flow against pressure gradients such as hyperaemic or basal stenosis resistance (HSR or BSR). More commonly coronary pressure measurements are used as a surrogate for flow measurement and techniques include iFR and fractional flow reserve (FFR). Cardiologists use a combination of these investigations together with the patient's history, symptoms and clinical risk factors to decide if a stenosis requires further treatment. An example of use in clinical practice is seen here. [1] iFR definition and calculation [ edit] iFR calculation uses a ratio of proximal and distal coronary pressures over the wave-free period in diastole The flow velocity, pressure, and instantaneous microvascular resistance were calculated over the wave-free period and during that of the complete cardiac cycle. Flow velocity is higher, and pressure is lower over the wave-free period. This results in lower microvascular resistance during the wave-free period in comparison to the complete cardiac cycle. Values are expressed as median+/-interquartile range. Used with permission: Sen S, Asrress KN, Nijjer S, et al. J Am Coll Cardiol 2013;61:1409–20. Instantaneous wave-free ratio is performed using high fidelity pressure wires that are passed distal to the coronary stenosis. iFR isolates a specific period in diastole, called the wave-free period, and uses the ratio of distal coronary pressure (Pd) to the pressure observed in the aorta (Pa) over this period. During this wave-free period, the competing forces (waves) that affect coronary flow are quiescent meaning pressure and flow are linearly related as compared to the rest of the cardiac cycle. [2] [3] When stenoses are flow limiting, Pd and Pa pressures over the wave-free period diverge; a normal ratio is 1. 0 and iFR values of below 0. 90 suggest flow limitation. iFR can be calculated using dedicated consoles available for medical use and typically uses an average over 5 heart beats but can be performed using a single heart beat. iFR is measured at rest, without the need for pharmacological vasodilators or stressors and compares well to other invasive and non-invasive markers of ischemia or flow limitation. [4] Studies [ edit] A number of studies using the Imperial College developed iFR algorithm have been conducted. The ADVISE study was a proof of concept study that demonstrated that the wave-free period, usually isolated using wave-intensity analysis, [5] could be reliably determined using a pressure-only approach. [6] This was shown across a variety of stenosis severities and demonstrated that over that specific period in diastole, microcirculatory resistance was the lowest and most stable compared to the rest of the cardiac cycle. During this specific period, pressure and flow are linearly related, allowing pressure-only inferences of transtenotic flow limitation. iFR was compared to the current clinically-used reference standard, FFR, and demonstrated good diagnostic lesion classification. Furthermore, iFR was consistent in utility for the left and right coronary artery, and the wave-free period was stable from beat-to-beat and even in the presence of arrhythmia. The study however was relatively underpowered to determine a clinical cut-point. The ADVISE-Registry was a larger study in which pressure wire data collected from patients undergoing functional assessment for clinical management, was analysed to compare iFR and FFR. [7] This study recognised that matching FFR was limited by the capacity of FFR to match itself with repeated measures and accordingly presented per-range agreements. An independent consecutive blinded comparison of iFR and FFR in Asian patients reported similar results. The CLARIFY study was a physiological study in which iFR and FFR were compared to an independent third measure, hyperaemic stenosis resistance (HSR) which uses a combination of pressure and flow assessment to detect ischemia. [8] Both measures compared equally well to this flow-based index. In stenoses classified as ischemic, the wave-free period provided a similar reduction in microvascular resistance as adenosine-mediated hyperaemia over the whole cardiac cycle. The Hybrid iFR-FFR approach has been proposed as method of minimising patient exposure to adenosine or other vasodilators. [9] In this approach, an iFR can be measured, and stenoses with an iFR >0. 93 may be deferred while those with an iFR <0. 86 can be treated by revascularization. Stenoses with an iFR between 0. 86-0. 93 can undergo an FFR assessment to guide therapy. This range can be changed by the physician according to how closely they want to match an FFR-classification of lesions. Using this typical range, almost 60% of stenoses can be spared from needing vasodilator infusion. ADVISE-II has prospectively assessed the hybrid approach in an independent international multi-centre study which confirmed the findings of the earlier Hybrid analysis. Interim results were reported by Javier Escaned at EuroPCR, the final findings were presented at TCT 2013. [10] These findings have been in keeping with an international collaborative study, RESOLVE, which pooled retrospective data from many centres worldwide with independent core-lab analysis of raw pressure traces. [11] Conflicting data, when re-analysed using the clinically available iFR-algorithms produced results similar to the ADVISE-Registry and ADVISE Hybrid studies. [12] iFR has also been compared to FFR and the resting Pd/Pa ratio in the post-coronary intervention setting. In a manner similar to FFR, iFR can be used to measure the haemodynamic change induced by stent placement and detect the impact of any residual stenoses. [13] The ADVISE-in-Practice study reported the first clinical experience of the commercially available iFR console. [14] Video examples of iFR technology in clinical use are available here [1]. iFR Clinical Outcome Studies [ edit] Two outcome studies, DEFINE-FLAIR [15] and the iFR-SWEDEHEART [16] will assess whether patient outcomes differ if stenoses are treated according to iFR or FFR classification of stenosis severity. DEFINE-FLAIR, which aims to recruit 2500 patients, will be the largest physiological study to date and will provide the first randomised data of the use of iFR and FFR in patients with both stable coronary disease and acute coronary syndromes. It will also provide the first randomised data of the clinical utility of FFR in guiding and deferring coronary intervention outside of the FAME and DEFER studies. Both DEFINE-FLAIR and iFR-SWEDEHEART have harmonised clinical endpoints which will enable combined analysis of over 4500 patients. SYTNAX II is a modern PCI study assessing the clinical utility of stenting three-vessel coronary disease. [17] Patients with three-vessel coronary disease whom the Heart Team decide are in equipoise between surgical revascularization or PCI intervention, undergo physiologically guided stenting. The SYNTAX II clinical risk calculator is used to determine equipoise. All major vessels undergo pressure wire assessment using the iFR-FFR hybrid approach, and only those positive for ischaemia undergo stenting. Intravascular ultrasound is used to ensure optimal stent delivery. Clinical outcomes will be compared to a historical surgical cohort from SYNTAX-I study. An example of a patient enrolled into the SYNTAX-II study is shown in this video. iFR physiological mapping of coronary vessels [ edit] The instantaneous wave-free ratio can also be calculated on a beat-to-beat basis. If performed during the slow withdrawal of a pressure wire (referred to as 'pullback') under resting conditions, it is possible to plot the change of iFR or trans-stenotic gradient over the wave-free period throughout the vessel. [18] [19] This can help identify focal and diffuse coronary disease potentially amenable to revascularisation. An example of pullback in clinical use can be seen in this video. The pressure wire data can be co-registered with the angiographic findings to aid ease of interpretation. With mechanised pullback approaches which move the pressure wire at a fixed speed, the physiological length of a stenosis can be determined. With advanced live co-registration this is also feasible with during manual pullback. Advanced computer processing can utilise iFR-pullback data to predict the hemodynamic consequences of performing percutaneous coronary intervention (PCI) to a chosen segment of the coronary vessel. The predicted iFR values produced by the virtual-PCI on the iFR-pullback are closely related to those observed after PCI in the coronary vessel. [18] This predictive capacity may provide added advantage to Interventional Cardiologists when assessing multiple coronary stenoses in a single vessel and planning the treatment approach. iFR-pullback technologies are undergoing evaluation in European centres. [20] Controversy [ edit] Alternative iFR computation systems have been proposed, for example incorporating part of systole into the definition of diastole and optionally different time-shifts between Pd and Pa signals, [21] yielding unsatisfactory results. [22] The same datasets reanalysed using the standard algorithms confirm the mainstream findings. [11] Various explanations have been proposed. [12] References [ edit] ^ "iFR FFR Hybrid assessment technique to evaluate ischaemia of intermediate coronary stenosis". YouTube. 2014-03-05. Retrieved 2016-05-20. ^ Sen, Sayan (31 March 2012). "Development and Validation of a New Adenosine-Independent Index of Stenosis Severity From Coronary Wave–Intensity Analysis". Journal of the American College of Cardiology. 59 (15): 1392–1402. doi: 10. 1016/. PMID 22154731. ^ Parker, Kim. "The instantaneous wave-free ratio (iFR)". Wave Intensity Analysis. Retrieved 2 March 2015. ^ Sen, Sayan (31 March 2013). "Diagnostic Classification of the Instantaneous Wave-Free Ratio Is Equivalent to Fractional Flow Reserve and Is Not Improved With Adenosine Administration". 61 (13): 1409–1420. PMID 23500218. ^ Sen, S; Petraco, R; Mayet, J; Davies, J (May 3, 2013). "Wave Intensity Analysis in the Human Coronary Circulation in Health and Disease". Current Cardiology Reviews. 10 (1): 17–23. 2174/1573403x10999140226121300. PMC 3968589. PMID 23642024. ^ Sen, S (Apr 10, 2012). "Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) study". 59 (15): 1392–402. PMID 22154731. ^ Petraco, R (May 20, 2013). "Classification performance of instantaneous wave-free ratio (iFR) and fractional flow reserve in a clinical population of intermediate coronary stenoses: results of the ADVISE registry". EuroIntervention. 9 (1): 91–101. 4244/eijv9i1a14. PMID 22917666. ^ Sen, S (Apr 2, 2013). "Diagnostic classification of the instantaneous wave-free ratio is equivalent to fractional flow reserve and is not improved with adenosine administration. Results of CLARIFY (Classification Accuracy of Pressure-Only Ratios Against Indices Using Flow Study)". 61 (13): 1409–20. PMID 23500218. ^ Petraco, R (Feb 22, 2013). "Hybrid iFR-FFR decision-making strategy: implications for enhancing universal adoption of physiology-guided coronary revascularisation". 8 (10): 1157–65. 4244/EIJV8I10A179. PMID 23256988. ^ "ADVISE-II Results announced". ^ a b Jeremias, A (Oct 22, 2013). "Multicenter Core Laboratory Comparison of the Instantaneous Wave-Free Ratio and Resting P d /P a with Fractional Flow Reserve: The RESOLVE Study". 63 (13): 1253–1261. PMID 24211503. ^ a b Nijjer, S. "RESOLVE could not verify the VERIFY study". Heart: published online 23 October 2013. Retrieved 18 November 2013. ^ Nijjer, SS (December 2013). "Improvement in coronary haemodynamics after percutaneous coronary intervention: assessment using instantaneous wave-free ratio". Heart. 99 (23): 1740–8. 1136/heartjnl-2013-304387. PMC 3841762. PMID 24047640. ^ Petraco, R; Al-Lamee, R; Gotberg, M; Sharp, A; Hellig, F; Nijjer, SS; Echavarria-Pinto, M; van de Hoef, TP; Sen, S; Tanaka, N; Van Belle, E; Bojara, W; Sakoda, K; Mates, M; Indolfi, C; De Rosa, S; Vrints, CJ; Haine, S; Yokoi, H; Ribichini, FL; Meuwissen, M; Matsuo, H; Janssens, L; Katsumi, U; Di Mario, C; Escaned, J; Piek, J; Davies, JE (November 2014). "Real-time use of instantaneous wave-free ratio: results of the ADVISE in-practice: an international, multicenter evaluation of instantaneous wave-free ratio in clinical practice". American Heart Journal. 168 (5): 739–48. PMC 4220017. PMID 25440803. ^ "Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation - Full Text View".. Retrieved 2016-05-20. ^ "Evaluation of iFR vs FFR in Stable Angina or Acute Coronary Syndrome - Full Text View".. Retrieved 2016-05-20. ^ "A Trial to Evaluate a New Strategy in the Functional Assessment of 3-vessel Disease Using the SYNTAX II Score in Patients Treated With PCI - Full Text View".. Retrieved 2016-05-20. ^ a b Nijjer, SS; Sen, S; Petraco, R; Escaned, J; Echavarria-Pinto, M; Broyd, C; Al-Lamee, R; Foin, N; Foale, RA; Malik, IS; Mikhail, GW; Sethi, AS; Al-Bustami, M; Kaprielian, RR; Khan, MA; Baker, CS; Bellamy, MF; Hughes, AD; Mayet, J; Francis, DP; Di Mario, C; Davies, JE (December 2014). "Pre-angioplasty instantaneous wave-free ratio pullback provides virtual intervention and predicts hemodynamic outcome for serial lesions and diffuse coronary artery disease". JACC. Cardiovascular Interventions. 7 (12): 1386–96. PMID 25459526. ^ Nijjer, Sukhjinder S. ; Sen, Sayan; Petraco, Ricardo; Mayet, Jamil; Francis, Darrel P. ; Davies, Justin E. R. (January 2015). "The Instantaneous wave-Free Ratio (iFR) pullback: A novel innovation using baseline physiology to optimise coronary angioplasty in tandem lesions". Cardiovascular Revascularization Medicine. 16 (3): 167–171. PMID 25977227. ^ "Drs Justin Davies and Iqbal Malik use IFR Scout to discriminate diffuse from focal coronary disease". 2015-01-28. Retrieved 2016-05-20. ^ Berry, Colin. "VERIFY: Definition of diastole". VERIFY. American College of Cardiology Foundation. Retrieved 18 December 2013. ^ Berry, C; van 't Veer, M; Witt, N; Kala, P; Bocek, O; Pyxaras, SA; McClure, JD; Fearon, WF; Barbato, E; Tonino, PA; De Bruyne, B; Pijls, NH; Oldroyd, KG (Apr 2, 2013). "VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice): a multicenter study in consecutive patients". 61 (13): 1421–7. PMID 23395076.
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