document_title: Cellular respiration

question_text: most of the atp produced during cellular respiration is produced by

text: Cellular respiration

text: Aerobic respiration

text: Aerobic respiration requires oxygen (O2) in order to create ATP. Although carbohydrates, fats, and proteins are consumed as reactants, it is the preferred method of pyruvate breakdown in glycolysis and requires that pyruvate enter the mitochondria in order to be fully oxidized by the Krebs cycle. The products of this process are carbon dioxide and water, but the energy transferred is used to break bonds in ADP as the third phosphate group is added to form ATP (adenosine triphosphate), by substrate-level phosphorylation, NADH and FADH2

text:
Simplified reaction:
C6H12O6 (s) + 6 O2 (g) → 6 CO2 (g) + 6 H2O (l) + heat

ΔG = −2880 kJ per mol of C6H12O6

text: The negative ΔG indicates that the reaction can occur spontaneously.

text: The potential of NADH and FADH2 is converted to more ATP through an electron transport chain with oxygen as the "terminal electron acceptor". Most of the ATP produced by aerobic cellular respiration is made by oxidative phosphorylation. This works by the energy released in the consumption of pyruvate being used to create a chemiosmotic potential by pumping protons across a membrane. This potential is then used to drive ATP synthase and produce ATP from ADP and a phosphate group. Biology textbooks often state that 38 ATP molecules can be made per oxidised glucose molecule during cellular respiration (2 from glycolysis, 2 from the Krebs cycle, and about 34 from the electron transport system).[2] However, this maximum yield is never quite reached because of losses due to leaky membranes as well as the cost of moving pyruvate and ADP into the mitochondrial matrix, and current estimates range around 29 to 30 ATP per glucose.[2]

text: Aerobic metabolism is up to 15 times more efficient than anaerobic metabolism (which yields 2 molecules ATP per 1 molecule glucose). However some anaerobic organisms, such as methanogens are able to continue with anaerobic respiration, yielding more ATP by using other inorganic molecules (not oxygen) as final electron acceptors in the electron transport chain. They share the initial pathway of glycolysis but aerobic metabolism continues with the Krebs cycle and oxidative phosphorylation. The post-glycolytic reactions take place in the mitochondria in eukaryotic cells, and in the cytoplasm in prokaryotic cells.

text: Glycolysis

text: Glycolysis is a metabolic pathway that takes place in the cytosol of cells in all living organisms. This pathway can function with or without the presence of oxygen. In humans, aerobic conditions produce pyruvate and anaerobic conditions produce lactate. In aerobic conditions, the process converts one molecule of glucose into two molecules of pyruvate (pyruvic acid), generating energy in the form of two net molecules of ATP. Four molecules of ATP per glucose are actually produced, however, two are consumed as part of the preparatory phase. The initial phosphorylation of glucose is required to increase the reactivity (decrease its stability) in order for the molecule to be cleaved into two pyruvate molecules by the enzyme aldolase. During the pay-off phase of glycolysis, four phosphate groups are transferred to ADP by substrate-level phosphorylation to make four ATP, and two NADH are produced when the pyruvate are oxidized. The overall reaction can be expressed this way:

text: Starting with glucose, 1 ATP is used to donate a phosphate to glucose to produce glucose 6-phosphate. Glycogen can be converted into glucose 6-phosphate as well with the help of glycogen phosphorylase. During energy metabolism, glucose 6-phosphate becomes fructose 6-phosphate. An additional ATP is used to phosphorylate fructose 6-phosphate into fructose 1,6-disphosphate by the help of phosphofructokinase. Fructose 1,6-diphosphate then splits into two phosphorylated molecules with three carbon chains which later degrades into pyruvate.

text: Glycolysis can be literally translated as "sugar splitting". [3]

text: Oxidative decarboxylation of pyruvate

text: Pyruvate is oxidized to acetyl-CoA and CO2 by the pyruvate dehydrogenase complex (PDC). The PDC contains multiple copies of three enzymes and is located in the mitochondria of eukaryotic cells and in the cytosol of prokaryotes. In the conversion of pyruvate to acetyl-CoA, one molecule of NADH and one molecule of CO2 is formed.

text: Citric acid cycle

text: This is also called the Krebs cycle or the tricarboxylic acid cycle. When oxygen is present, acetyl-CoA is produced from the pyruvate molecules created from glycolysis. Once acetyl-CoA is formed, aerobic or anaerobic respiration can occur. [4] When oxygen is present, the mitochondria will undergo aerobic respiration which leads to the Krebs cycle. However, if oxygen is not present, fermentation of the pyruvate molecule will occur. In the presence of oxygen, when acetyl-CoA is produced, the molecule then enters the citric acid cycle (Krebs cycle) inside the mitochondrial matrix, and is oxidized to CO2 while at the same time reducing NAD to NADH. NADH can be used by the electron transport chain to create further ATP as part of oxidative phosphorylation. To fully oxidize the equivalent of one glucose molecule, two acetyl-CoA must be metabolized by the Krebs cycle. Two waste products, H2O and CO2, are created during this cycle.

text: The citric acid cycle is an 8-step process involving 18 different enzymes and co-enzymes. [4] During the cycle, acetyl-CoA (2 carbons) + oxaloacetate (4 carbons) yields citrate (6 carbons), which is rearranged to a more reactive form called isocitrate (6 carbons). Isocitrate is modified to become α-ketoglutarate (5 carbons), succinyl-CoA, succinate, fumarate, malate, and, finally, oxaloacetate.

text: The net gain of high-energy compounds from one cycle is 3 NADH, 1 FADH2, and 1 GTP; the GTP may subsequently be used to produce ATP. Thus, the total yield from 1 glucose molecule (2 pyruvate molecules) is 6 NADH, 2 FADH2, and 2 ATP.

text: Oxidative phosphorylation

text: In eukaryotes, oxidative phosphorylation occurs in the mitochondrial cristae. It comprises the electron transport chain that establishes a proton gradient (chemiosmotic potential) across the boundary of inner membrane by oxidizing the NADH produced from the Krebs cycle. ATP is synthesized by the ATP synthase enzyme when the chemiosmotic gradient is used to drive the phosphorylation of ADP. The electrons are finally transferred to exogenous oxygen and, with the addition of two protons, water is formed.

text: Efficiency of ATP production

text: The table below describes the reactions involved when one glucose molecule is fully oxidized into carbon dioxide. It is assumed that all the reduced coenzymes are oxidized by the electron transport chain and used for oxidative phosphorylation.

text:
Step
coenzyme yield
ATP yield
Source of ATP

Glycolysis preparatory phase

−2
Phosphorylation of glucose and fructose 6-phosphate uses two ATP from the cytoplasm.

Glycolysis pay-off phase

4
Substrate-level phosphorylation

2 NADH
3 or 5
Oxidative phosphorylation : Each NADH produces net 1.5 ATP (instead of usual 2.5) due to NADH transport over the mitochondrial membrane

Oxidative decarboxylation of pyruvate
2 NADH
5
Oxidative phosphorylation

Krebs cycle

2
Substrate-level phosphorylation

6 NADH
15
Oxidative phosphorylation

2 FADH2
3
Oxidative phosphorylation

Total yield
30 or 32 ATP
From the complete oxidation of one glucose molecule to carbon dioxide and oxidation of all the reduced coenzymes.

text: Although there is a theoretical yield of 38 ATP molecules per glucose during cellular respiration, such conditions are generally not realized because of losses such as the cost of moving pyruvate (from glycolysis), phosphate, and ADP (substrates for ATP synthesis) into the mitochondria. All are actively transported using carriers that utilize the stored energy in the proton electrochemical gradient.

text:
Pyruvate is taken up by a specific, low Km transporter to bring it into the mitochondrial matrix for oxidation by the pyruvate dehydrogenase complex.
The phosphate carrier (PiC) mediates the electroneutral exchange (antiport) of phosphate (H2PO4−; Pi) for OH− or symport of phosphate and protons (H+) across the inner membrane, and the driving force for moving phosphate ions into the mitochondria is the proton motive force.
The ATP-ADP translocase (also called adenine nucleotide translocase, ANT) is an antiporter and exchanges ADP and ATP across the inner membrane. The driving force is due to the ATP (−4) having a more negative charge than the ADP (−3), and thus it dissipates some of the electrical component of the proton electrochemical gradient.

text: The outcome of these transport processes using the proton electrochemical gradient is that more than 3 H+ are needed to make 1 ATP. Obviously this reduces the theoretical efficiency of the whole process and the likely maximum is closer to 28–30 ATP molecules.[2] In practice the efficiency may be even lower because the inner membrane of the mitochondria is slightly leaky to protons.[5] Other factors may also dissipate the proton gradient creating an apparently leaky mitochondria. An uncoupling protein known as thermogenin is expressed in some cell types and is a channel that can transport protons. When this protein is active in the inner membrane it short circuits the coupling between the electron transport chain and ATP synthesis. The potential energy from the proton gradient is not used to make ATP but generates heat. This is particularly important in brown fat thermogenesis of newborn and hibernating mammals.

text: According to some of newer sources the ATP yield during aerobic respiration is not 36–38, but only about 30–32 ATP molecules / 1 molecule of glucose [6], because:

text:
ATP : NADH+H+ and ATP : FADH2 ratios during the oxidative phosphorylation appear to be not 3 and 2, but 2.5 and 1.5 respectively. Unlike in the substrate-level phosphorylation, the stoichiometry here is difficult to establish.

ATP synthase produces 1 ATP / 3 H+. However the exchange of matrix ATP for cytosolic ADP and Pi (antiport with OH− or symport with H+) mediated by ATP–ADP translocase and phosphate carrier consumes 1 H+ / 1 ATP as a result of regeneration of the transmembrane potential changed during this transfer, so the net ratio is 1 ATP : 4 H+.
The mitochondrial electron transport chain proton pump transfers across the inner membrane 10 H+ / 1 NADH+H+ (4 + 2 + 4) or 6 H+ / 1 FADH2 (2 + 4).

text:
ATP : NADH+H+ coming from glycolysis ratio during the oxidative phosphorylation is

1.5, as for FADH2, if hydrogen atoms (2H++2e−) are transferred from cytosolic NADH+H+ to mitochondrial FAD by the glycerol phosphate shuttle located in the inner mitochondrial membrane.
2.5 in case of malate-aspartate shuttle transferring hydrogen atoms from cytosolic NADH+H+ to mitochondrial NAD+

text: So finally we have, per molecule of glucose

text:
Substrate-level phosphorylation: 2 ATP from glycolysis + 2 ATP (directly GTP) from Krebs cycle
Oxidative phosphorylation

2 NADH+H+ from glycolysis: 2 × 1.5 ATP (if glycerol phosphate shuttle transfers hydrogen atoms) or 2 × 2.5 ATP (malate-aspartate shuttle)
2 NADH+H+ from the oxidative decarboxylation of pyruvate and 6 from Krebs cycle: 8 × 2.5 ATP
2 FADH2 from the Krebs cycle: 2 × 1.5 ATP

text: Altogether this gives 4 + 3 (or 5) + 20 + 3 = 30 (or 32) ATP per molecule of glucose

text: The total ATP yield in ethanol or lactic acid fermentation is only 2 molecules coming from glycolysis, because pyruvate is not transferred to the mitochondrion and finally oxidized to the carbon dioxide (CO2), but reduced to ethanol or lactic acid in the cytoplasm.[6]

text: Fermentation

text: Without oxygen, pyruvate (pyruvic acid) is not metabolized by cellular respiration but undergoes a process of fermentation. The pyruvate is not transported into the mitochondrion, but remains in the cytoplasm, where it is converted to waste products that may be removed from the cell. This serves the purpose of oxidizing the electron carriers so that they can perform glycolysis again and removing the excess pyruvate. Fermentation oxidizes NADH to NAD+ so it can be re-used in glycolysis. In the absence of oxygen, fermentation prevents the buildup of NADH in the cytoplasm and provides NAD+ for glycolysis. This waste product varies depending on the organism. In skeletal muscles, the waste product is lactic acid. This type of fermentation is called lactic acid fermentation. In strenuous exercise, when energy demands exceed energy supply, the respiratory chain cannot process all of the hydrogen atoms joined by NADH. During anaerobic glycolysis, NAD+ regenerates when pairs of hydrogen combine with pyruvate to form lactate. Lactate formation is catalyzed by lactate dehydrogenase in a reversible reaction. Lactate can also be used as an indirect precursor for liver glycogen. During recovery, when oxygen becomes available, NAD+ attaches to hydrogen from lactate to form ATP. In yeast, the waste products are ethanol and carbon dioxide. This type of fermentation is known as alcoholic or ethanol fermentation. The ATP generated in this process is made by substrate-level phosphorylation, which does not require oxygen.

text: Fermentation is less efficient at using the energy from glucose: only 2 ATP are produced per glucose, compared to the 38 ATP per glucose nominally produced by aerobic respiration. This is because the waste products of fermentation still contain chemical potential energy that can be released by oxidation. Ethanol, for example, can be burned in an internal combustion engine like gasoline. Glycolytic ATP, however, is created more quickly. For prokaryotes to continue a rapid growth rate when they are shifted from an aerobic environment to an anaerobic environment, they must increase the rate of the glycolytic reactions. For multicellular organisms, during short bursts of strenuous activity, muscle cells use fermentation to supplement the ATP production from the slower aerobic respiration, so fermentation may be used by a cell even before the oxygen levels are depleted, as is the case in sports that do not require athletes to pace themselves, such as sprinting.

text: Anaerobic respiration

text: Cellular respiration is the process by which biological fuels are oxidised in the presence of an inorganic electron acceptor (such as oxygen) to produce large amounts of energy, to drive the bulk production of ATP.

text: Anaerobic respiration is used by some microorganisms in which neither oxygen (aerobic respiration) nor pyruvate derivatives (fermentation) is the final electron acceptor. Rather, an inorganic acceptor such as sulfate or nitrate is used. Such organisms are typically found in unusual places such as underwater caves or near hydrothermal vents at the bottom of the ocean.


document_title: Liverpool F.C. in European football

question_text: when did liverpool last win the european champions league

root

text: Liverpool F.C. in European football

text: Background[edit]

text: Club competitions between teams from different European countries can trace their origins as far back as 1897, when the Challenge Cup was created for clubs in the Austro-Hungarian Empire, who did not meet under normal circumstances. The Sir Thomas Lipton Trophy, named after entrepreneur and sportsman Thomas Lipton, was established in 1909 and was contested between clubs from Italy, Great Britain, Germany and Switzerland; the competition lasted for two years.[1] The earliest attempt to create a cup for national champion clubs of Europe was made by Swiss club FC Servette. Founded in 1930, the Coupe des Nations featured clubs of ten major European football leagues and was deemed a success. Due to financial reasons, the competition was abandoned.[2]

tag: p

text: The first continental competition organised by UEFA was the European Cup in 1955. Conceived by Gabriel Hanot, the editor of L'Équipe, as a competition for winners of the European national football leagues, it is considered the most prestigious European football competition.[3][4] When the European Cup was first played, Liverpool were in the Second Division, following relegation from the First Division after the 1953–54 season, and thus were ineligible for the competition.[5] During their time in the Second Division, two further competitions were created: the Inter-Cities Fairs Cup and UEFA Cup Winners' Cup. Established in 1955, the Inter-Cities Fairs Cup was later re-branded as the UEFA Cup when it came under the auspices of UEFA in 1971.[6] Since the 2009–10 season, the competition has been known as the UEFA Europa League.[7] The UEFA Cup Winners' Cup was inaugurated in 1960 for the winners of domestic cup competitions.[6]

text: In 1962 Liverpool were promoted to the First Division. Two years later, they won the Football League championship, thus making their European debut in the 1964–65 European Cup. In the following years, further European competitions were inaugurated. The first, the UEFA Super Cup, was originally a match played between the winners of the European Cup and the Cup Winners' Cup. First established in 1973, it changed formats in 2000; since then, it has been contested between the winners of the Champions League (formerly the European Cup) and the Europa League (formerly the UEFA Cup), following the Cup Winners' Cup amalgamation into the latter.[8] The Intercontinental Cup was a competition for the winners of the European Cup (later, the UEFA Champions League) and the South American equivalent, the Copa Libertadores. Established in 1960, the Intercontinental Cup was jointly organised by UEFA and the Confederación Sudamericana de Fútbol (CONMEBOL). It ran until 2004, when the FIFA Club World Cup, which includes the winners of all six confederations' regional championships replaced it.[9]

text: History[edit]

text: First steps in Europe – the Shankly years (1965–74)[edit]

text: Bill Shankly began managing Liverpool in 1959, and it was under him that the team first competed in European competition in 1964–65, qualifying for the European Cup by winning the First Division championship the previous season.[10] The club's first opponents were Knattspyrnufélag Reykjavíkur of Iceland, who they played in the preliminary round. Liverpool won 11–1 on aggregate. The next round, against Belgian club Anderlecht, was the first time in Liverpool's history that they wore their now common all-red strip. The decision was made to change from red shirts, white shorts and socks by Shankly, who wanted his players to make more of a psychological impact on opponents.[11] They beat Anderlecht and progressed to the semi-finals, where they met Italian team Internazionale. Before the first leg at Anfield, Shankly asked two injured players to parade the FA Cup, which Liverpool had won the previous week, to intimidate the Italians.[12] The team won the match 3–1,[13] but Inter won the second leg 3–0, securing a 4–3 aggregate victory. The second leg was controversial; Shankly described it as "a war".[14] He felt that the referee, Jose Maria Ortiz de Mendibel, had shown bias towards Internazionale,[15] and the Liverpool players felt cheated by his decisions.[14] The club's 1964–65 FA Cup victory ensured qualification for the UEFA Cup Winners' Cup the following season, and in that competition, they reached their first European final. Borussia Dortmund, Liverpool's opponents, employed counter-attacking tactics that had paid dividends in previous rounds and did so again, with the West Germans beating Liverpool 2–1 after extra time.[16]

text: In the next four seasons, they competed in the European Cup and Inter-Cities Fairs Cup, but failed to progress past the third round in either competition.[17] A tie against Dutch team Ajax during the 1966–67 European Cup was to prove pivotal in the history of Liverpool in European competition.[18] Ajax beat Liverpool 7–3 on aggregate. However, the style of football that Ajax played – a patient passing game, inspired by Johann Cruyff – convinced Shankly that Liverpool had to replicate this style to be successful in Europe.[19] Liverpool reached the semi-finals of the 1970–71 Inter-Cities Fairs Cup, losing 1–0 on aggregate to Leeds United.[20] They competed in the 1971–72 European Cup Winners' Cup, despite losing the 1971 FA Cup Final, as the FA Cup winners, Arsenal, had also qualified for the European Cup by winning the league championship. Liverpool were eliminated in the second round by Bayern Munich of Germany, losing 3–1 on aggregate.[21]

text: The changes made to Liverpool's tactics came to fruition during the 1972–73 UEFA Cup. The club reached their second European final, where they faced Borussia Mönchengladbach of Germany. Liverpool won the first leg 3–0 as a result of two goals from Kevin Keegan and one from Larry Lloyd. Victory in this first leg meant Liverpool only needed to avoid losing by three or more goals in order to win the final. This influenced their tactics – The Times reported that Liverpool employed a "holding action" against the "attacking Germans".[22] The tactics worked, allowing Mönchengladbach only two goals, granting Liverpool a 3–2 aggregate victory.[23] Liverpool also won the First Division championship that season, and as a result qualified for the 1973–74 European Cup, where they were eliminated in the second round by Red Star Belgrade of Yugoslavia. At the end of that season, Shankly retired.[24]

text: European domination – the Paisley years (1974–83)[edit]

text: Shankly was succeeded by his assistant, Bob Paisley, in 1974.[25] Liverpool competed in the Cup Winners' Cup during Paisley's first season and defeated Strømsgodset of Norway 11–0 at Anfield. This remains the club's largest margin of victory in all matches.[26] They lost in the next round to Hungarian side Ferencváros on the away goals rule. In 1975–76 the club entered the UEFA Cup after a second-place finish in the First Division. Victories over Hibernian (Scotland), Real Sociedad (Spain), Śląsk Wrocław (Poland), Dynamo Dresden (East Germany) and Barcelona (Spain) took Liverpool to their third European final. Crucial to their progress was goalkeeper Ray Clemence, who made two important penalty saves against Hibernian and Dresden, saving Liverpool from elimination on the away goals rule on both occasions.[27] Their opponents in the final were Club Brugge of Belgium. Liverpool recovered from a two-goal deficit to win the first leg at Anfield 3–2, with Ray Kennedy, Jimmy Case, and Keegan scoring a goal each in a span of six minutes. A 1–1 draw at the Jan Breydel Stadion in Bruges meant Liverpool won 4–3 on aggregate, earning their second UEFA Cup.[28]

text: As the 1975–76 league champions, the club entered the 1976–77 European Cup. They defeated Crusaders of Northern Ireland and Trabzonspor of Turkey to reach the quarter-finals, where they faced the runners-up from the previous season, Saint-Étienne. The French team won the first leg 1–0. The second leg at Anfield began well for Liverpool when Keegan scored in the first two minutes. Saint-Étienne equalised to make the score 2–1 on aggregate in their favour. Kennedy scored for Liverpool, but the away goals rule meant they still needed another goal to win the tie. With six minutes remaining, David Fairclough was brought on to replace John Toshack; he immediately scored in front of the Kop, ensuring a 3–2 aggregate victory for Liverpool.[29] In the semi-finals, they defeated FC Zürich of Switzerland 6–1 on aggregate to reach the final, where they met their opponents from the 1973 UEFA Cup Final, Borussia Mönchengladbach. The final was held in Rome, four days after the club had lost the 1977 FA Cup Final to Manchester United. Before the match, Paisley announced that striker Toshack would be fit to start. However, he was not named in the matchday squad. This change upset the Germans' game plan and allowed Keegan to torment his marker, Berti Vogts.[30] Liverpool won 3–1 to become European champions for the first time.[31]

text: By winning the European Cup, they qualified for the European Super Cup and played the winners of the Cup Winners' Cup, German team Hamburg, who had just signed Keegan.[32] Liverpool won the tie 7–1 on aggregate.[33] Liverpool entered the 1977–78 European Cup as champions and received a bye in the first round. They defeated Dynamo Dresden and Portuguese team Benfica in the second round and quarter-finals, respectively. In the semi-final, the club again met Borussia Mönchengladbach, who won the first leg 2–1. Liverpool won the second leg 3–0, progressing to a second successive European Cup final, this time against Club Brugge at Wembley Stadium in London. In the final Kenny Dalglish, who had been signed to replace Keegan, scored the winning goal after receiving the ball from a Graeme Souness pass. The 1–0 victory meant Liverpool became the first British team to retain the European Cup.[34] They faced Anderlecht in the 1978 European Super Cup, but failed to retain the trophy, losing 4–3 on aggregate against the Belgian side.[35] Liverpool were eliminated in the first round of the 1978–79 European Cup by English champions Nottingham Forest. Nottingham Forest won the tie 2–0 on aggregate, and went on to win the competition.[36] Liverpool entered the 1979–80 European Cup as English champions but were again eliminated in the first round, this time beaten 4–2 on aggregate by Dinamo Tbilisi of the Soviet Union.[37]

text: Liverpool participated in the 1980–81 European Cup as English league champions, defeating Finnish champions Oulun Palloseura, Scottish club Aberdeen and CSKA Sofia of Bulgaria to qualify for the semi-finals, where they faced three-time champions Bayern Munich. The first leg at Anfield finished goalless. In the second leg at the Olympiastadion in Munich, Ray Kennedy scored in the 83rd minute and, although the German side equalised, Liverpool went through to the final on the away goals rule.[38] They faced Spanish side Real Madrid in the final, held at the Parc des Princes in Paris. Alan Kennedy scored the only goal to give Liverpool a 1–0 victory, which secured the club's—and Paisley's—third European Cup. As champions of Europe, Liverpool competed in the Intercontinental Cup against South American champions Flamengo of Brazil. Liverpool lost the match 3–0.[39] The club's defence of the European Cup in 1981–82 was ended by CSKA Sofia in the quarter-finals.[40] Another quarter-final exit occurred in the 1982–83 European Cup when Polish club Widzew Łódź eliminated Liverpool 4–3 on aggregate.[41] Paisley retired as manager at the end of the season and was succeeded by his assistant, Joe Fagan.[42]

text: Triumph and tragedy – the Fagan years (1983–85)[edit]

text: Liverpool entered the 1983–84 European Cup as league champions for the fourth time in five seasons. Victories over Odense of Denmark and Spanish champions Athletic Bilbao brought Liverpool to face Portuguese champions Benfica in the quarter-finals.[43] Liverpool won the first leg at Anfield 1–0. In the second leg, their tactic of withdrawing Dalglish into midfield put Benfica's game plan into disarray,[44] leading to a 4–1 match victory and a 5–1 aggregate victory. Their opponents in the semi-finals were Dinamo București of Romania. The tie proved a brutal encounter, characterised by Souness breaking the jaw of the Bucharest captain Lică Movilă, and was won 3–1 on aggregate by Liverpool.[44]

text: Fagan's first season in charge of Liverpool had been a successful one. When they reached their fourth European Cup final, they had already won the Football League Cup and the league championship;[45] victory in the European final against Italian side Roma would complete an unprecedented treble. The final was played at Rome's Stadio Olimpico, and Liverpool went ahead in the 13th minute when Phil Neal scored, though Roma equalised towards the end of the first half. The score remained the same throughout full and extra time; Liverpool won the subsequent penalty shoot-out, with Alan Kennedy scoring the winning penalty after goalkeeper Bruce Grobbelaar had put off Francesco Graziani, causing him to place his penalty over the crossbar.[46] After the game, gangs of Roma fans assaulted Liverpool supporters travelling back to their hotels.[47] Success in the European Cup entitled Liverpool to compete in the 1984 Intercontinental Cup. However, they were unable to beat the winners of the Copa Libertadores, Independiente of Argentina, who claimed a 1–0 victory.[48]

text: Liverpool entered the 1984–85 European Cup as champions, and once again progressed to the final, where their opponents were Juventus of Italy. They aimed to win their fifth European Cup and keep the trophy. The 1985 European Cup Final was held at the Heysel Stadium in Brussels. The choice of venue had been criticised due to the dilapidated state of the stadium, and the club tried to persuade UEFA to change the venue.[49] Before the kick-off, Liverpool fans breached a fence separating the two groups of supporters and charged the Juventus fans. The resulting weight of people caused a retaining wall to collapse, killing 39 people and injuring hundreds more.[50] Despite calls for an abandonment, the match was played, as it was felt that further trouble would be caused otherwise.[51]

text: Juventus won the match 1–0; Michel Platini scored from the penalty spot to give Juventus their first European Cup.[52] UEFA laid the blame for the incident solely on the Liverpool fans: the official UEFA observer stated, "Only the English fans were responsible. Of that there is no doubt".[53] Three days after the final, UEFA banned all English clubs from European competition for an indefinite period. Liverpool were initially given an additional three-year ban.[52] Fagan retired after the 1984–85 season and was succeeded by Dalglish, who took over as player-manager.[54]

text: The ban on English clubs in European competitions ultimately lasted for five years, and even when the ban was lifted in 1990, Liverpool were not re-admitted; they had to serve an extra year. The ban prevented them qualifying for the European Cup in 1986 (as league champions and FA Cup winners), the UEFA Cup in 1987 (as league runners-up), the European Cup in 1988 (as league champions), the European Cup Winners' Cup in 1989 (as FA Cup winners) and the European Cup in 1990 (as league champions).[55]

text: Return to Europe (1991–2004)[edit]

text: Liverpool were allowed to return to European competition in the 1991–92 season, a year later than other English clubs. They qualified for the UEFA Cup as runners-up in the English league. Their manager by this stage was Graeme Souness, who had taken over towards the end of the previous season following Dalglish's resignation.[56]

text: Their first match, in the UEFA Cup, was against Finnish side Kuusyi Lahti, which they won 6–1.[57] A 6–2 aggregate victory set up a tie against Auxerre of France in the second round who they beat 3–2 on aggregate.[58] The club defeated Swarovski Tirol of Austria in the third round 6–0 on aggregate before losing to Genoa (Italy) 4–1 over two legs in the quarter finals.[59]

text: Liverpool's victory over Sunderland in the 1992 FA Cup Final qualified them for the 1992–93 European Cup Winners' Cup, but this campaign was short-lived, as they were eliminated in the second round by Russian side Spartak Moscow.[60] Liverpool finished no higher than sixth in the Premier League during the next two seasons, thus failing to qualify for European competition. In the 1995–96 season, they entered the UEFA Cup, but again progressed no further than the second round, this time losing to Brøndby of Denmark.[61]

text: As runners-up to League champions Manchester United in the 1996 FA Cup Final, Liverpool were able to compete in the 1996–97 UEFA Cup Winners' Cup. This proved the club's most successful campaign since their return to European competition, as they reached the semi-finals, where they were eliminated 3–2 on aggregate by Paris Saint–Germain.[62] In the next two seasons, Liverpool played in the UEFA Cup but were eliminated at an early stage of the competition, by Strasbourg and Celta de Vigo, respectively.[63][64] A seventh-place finish in the 1998–99 FA Premier League meant the club did not qualify for Europe in 1999–2000.[65]

text:
Having finished fourth in the 1999–2000 FA Premier League, Liverpool qualified for the 2000–01 UEFA Cup. Their victory in this competition marked a third win for a club. The entire season was the club's most successful since the 1983–84 season, as they won a cup treble consisting of the UEFA Cup, the FA Cup and the League Cup. Their opponents in the final in Dortmund were Alavés of Spain. The match was tied at 4–4 in extra time when Alavés defender Delfí Geli scored an own goal to give Liverpool victory on the golden goal rule.[66]
The performance of Gary McAllister, whose free-kick resulted in the winning goal, was praised as "outstanding" by Trevor Brooking.[67] This was the club's first European trophy since their European Cup victory in 1984.[68] As UEFA Cup winners, Liverpool played in the 2001 UEFA Super Cup against Champions League winners Bayern Munich and won 3–2.[69]

text: In the 2001–02 season, Liverpool returned to the European Cup, now called the UEFA Champions League, for the first time since the Heysel disaster. A 2–0 victory over Roma in the second group stage meant they progressed to the quarter-finals.[70] They faced German club Bayer Leverkusen and won the first leg 1–0. The outlook for the second leg appeared to be to Liverpool's advantage, as their counter-attacking style of play had served them well during away matches throughout the season;[71] however, they lost the second leg 4–2 and were eliminated 4–3 on aggregate.[72]

text: A second-place finish in the 2001–02 FA Premier League entitled Liverpool to participate in the Champions League for a second successive season, but they only finished third in their group and were eliminated from the competition.[73] The third-place finish meant they entered the 2002–03 UEFA Cup. Liverpool beat Dutch team Vitesse Arnhem and Auxerre to set up an all-British tie with Scottish team Celtic. A 1–1 draw in the first leg meant Liverpool would progress to the semi-finals if they did not concede a goal in the second leg at Anfield. However, Celtic scored before half-time and again in the second half to win 3–1 on aggregate.[74]

text: Liverpool entered the UEFA Cup for the 2003–04 season, after Chelsea beat them on the final day of the previous league season to claim the fourth place needed to qualify for the Champions League.[75] Liverpool were eliminated in the fourth round by eventual runners-up Marseille of France. At the end of the season, manager Gérard Houllier was replaced by Rafael Benítez.[76]

text: Renewed European success – the Benítez years (2004–10)[edit]

text: Liverpool had finished fourth in the 2003–04 season, which qualified them to compete in the Champions League in the 2004–05 season. A poor start in the group stages, with two losses in their first five games, had the club facing elimination. A 3–1 victory over Greek side Olympiacos, however, eventually ensured their passage to the knock-out rounds. Liverpool beat Bayer Leverkusen and Juventus to reach the semi-finals, and progressed to the final after they beat Chelsea 1–0 on aggregate; the goal scored by Luis García was referred to as a "ghost goal" by Chelsea manager José Mourinho, as it was unclear whether the ball crossed the goal line.[77] Liverpool's performances in Europe contrasted strongly with their league form, where they struggled to finish in the top-four and thus ensure qualification for the next Champions League season.[78]

text: Liverpool faced six-time European champions Milan in the final at the Atatürk Stadium in Istanbul on 25 May 2005. Trailing 3–0 at half-time, they scored three goals in a six-minute spell in the second half to level the score at 3–3. There were no goals during extra time, so the match was decided by a penalty shoot-out. With the shoot-out score at 3–2, Liverpool goalkeeper Jerzy Dudek saved Andriy Shevchenko's penalty to give Liverpool victory.[79] The nature of Liverpool's comeback victory has led to the match being referred to as the "miracle of Istanbul."[80] As this was the club's fifth European Cup victory, Liverpool were allowed to keep the European Champion Clubs' Cup permanently, and a new trophy was commissioned for the following year's competition.[81] The victory also entitled Liverpool to compete in the 2005 UEFA Super Cup at Stade Louis II, Monaco in August. They defeated UEFA Cup winners CSKA Moscow of Russia 3–1(aet.) to win their third Super Cup.[82] Their success in the Champions League meant Liverpool also qualified for the 2005 FIFA Club World Championship, where they lost 1–0 in the final to Brazilian team São Paulo.[83]

text: A fifth-place finish in the Premier League in 2004–05 meant Liverpool were not guaranteed entry into the Champions League, and faced the prospect of not being able to defend their European title. UEFA eventually ruled that they would be allowed to do so, but would be required to start in the first qualifying round, with no country protection, meaning they could face a team from England in the group stages.[84] This turned out to be the case—Liverpool advanced through three qualifying rounds and were drawn with Chelsea in the group stages. They progressed from their group as winners but were beaten by Benfica in the first knock-out round.[85]

text: In the 2006–07 Champions League, Liverpool progressed from the group stages and beat holders Barcelona, PSV and Chelsea to face Milan in a rematch of the 2005 final.[86] The Liverpool team, which contained only five players from the 2005 final, enjoyed more possession than in 2005,[87] but two goals from Filippo Inzaghi gave Milan their seventh European Cup in a 2–1 win.[88]

text: Liverpool were eliminated from the 2007–08 Champions League in the semi-finals by Chelsea, who they had beaten in the semi-finals in 2005 and 2007. A fourth-place finish in the 2007–08 Premier League secured their entry into the 2008–09 Champions League. Liverpool reached the quarter-finals and again faced Chelsea, but lost 7–5 on aggregate.[89]

text: A second-place finish in the 2008–09 Premier League entitled Liverpool to compete in the 2009–10 UEFA Champions League, but their campaign was short-lived; they finished third in their group, and were eliminated from the competition. They entered the 2009–10 UEFA Europa League, progressing to the semi-finals, where they were eliminated by eventual winners Atlético Madrid of Spain on the away goals rule after the tie finished 2–2 on aggregate.[90]

text: Decline and Resurgence (2010–present)[edit]

text: Rafael Benítez left the club at the end of the 2009–10 season and was replaced by Roy Hodgson.[91] A seventh-place finish in the 2009–10 Premier League meant Liverpool would be competing in the 2010–11 Europa League. They beat Rabotnički of Macedonia and Trabzonspor of Turkey to progress to the group stage, where Liverpool were drawn alongside Napoli, FC Utrecht and Steaua București. They won two games and drew four to finish top of their group with ten points and progress to the round of 32.[92] They were drawn against Sparta Prague in the next round. Before the tie was played, however, Hodgson was replaced by former manager Kenny Dalglish, who initially served as a caretaker manager.[93] A 1–0 aggregate victory ensured progression to the round of 16, in which Liverpool lost 1–0 on aggregate to eventual runners-up Braga.[94] A sixth-place finish in the 2010–11 Premier League meant the club failed to qualify for European competition for the first time since 1999.[95] On the following season, victory in the League Cup final ensured Liverpool a place in the 2012–13 Europa League.[96]

text: Liverpool qualified for the knockout phase of the 2012–13 Europa League after winning their group at the group stage, but were eliminated from the competition at the round of 32 by Zenit Saint Petersburg on the away goals rule after a 0–2 loss away and a 3–1 win at home.[97] A seventh-place finish in the 2012–13 Premier League and a failure to secure qualification via domestic cups meant Liverpool failed to qualify for any European competition in the 2013–14 season. A second-placed finish in the 2013–14 Premier League, ensured Liverpool qualified for the group stage of the 2014–15 Champions League.[98] One win out of six in the group stage meant they were eliminated and entered into the knockout phase of the 2014–15 Europa League.[99] The campaign was short-lived, as Liverpool eliminated by Beşiktaş in the round of 32.[100]

text:
Finishing sixth in the 2014–15 Premier League qualified Liverpool directly to the group stage of the 2015–16 Europa League, where they faced Sion, Bordeaux and for the first time, Russian side Rubin Kazan.[101] During the group stage, manager Brendan Rodgers was replaced by Jürgen Klopp.[102]  After winning the group, Liverpool qualified for the knockout phase, beating FC Augsburg in the round of 32 before facing bitter rivals Manchester United in the round of 16, the two clubs' first meeting in Europe.[103][104] Liverpool defeated them 3–1 on aggregate and victory led to a quarter-final tie with Klopp's former team Borussia Dortmund.[105][106] After a 1–1 draw in the first leg at Signal Iduna Park, Dortmund went 3–1 up in the return leg at Anfield with 33 minutes remaining, requiring Liverpool to score three goals due to the Away goals rule. Goals from Philippe Coutinho, Mamadou Sakho and a last minute winner from Dejan Lovren, however, saw Liverpool complete the comeback and qualify for their first European semi-final since 2010.[107] There they faced Villarreal, completing a second comeback after overturning a 1–0 defeat in the first leg at El Madrigal to qualify for the final with a 3–1 aggregate win.[108][109] Liverpool played Sevilla in the final at St. Jakob-Park, Basel, on 18 May, losing 3–1. A 4th-place finish in the 2016–17 Premier League qualified Liverpool for the 2017–18 UEFA Champions League and a return to Europe's premier club tournament for only the second time in 8 years during the 2010s.
On 17 October 2017, Liverpool won 7-0 away to Maribor in the third round of matches of the group stage of the 2017–18 UEFA Champions League. The win was a record away win for Liverpool in European competitions and also the biggest away win by an English team in the history of the European Cup.[110][111] After qualifying top of their group, they proceeded to defeat Porto 5-0 at the Estadio de Dragao, before holding them to a 0-0 draw on the return leg, then defeated domestic rivals Manchester City 3-0 and 2-1, and in the semi-finals, defeated Roma 5-2 at Anfield, before a 4-2 loss led to a 7-6 aggregate win, taking them to the final, against holders Real Madrid. Liverpool lost the final by 3-1 but finished 4th in the 2017–18 Premier League to qualify for the 2018–19 UEFA Champions League.[112]

text: Records[edit]

text:
Most appearances in European competition: Jamie Carragher, 150[113]
Most goals in European competition: Steven Gerrard, 41[114]
First European match: Liverpool 6–0 Knattspyrnufélag Reykjavíkur, European Cup, first round, 17 August 1964[115]
First goal scored in Europe: Gordon Wallace, against KR Reykjavik[116]
Biggest win: Liverpool 11–0 Strømsgodset, in the UEFA Cup Winners' Cup, 17 September 1974[115]
Biggest defeat: Liverpool 1–5 Ajax, in the European Cup, 7 December 1966[117]
Highest European home attendance: 55,104, against Barcelona in the 1975–76 UEFA Cup, 14 April 1976[118][119]
Lowest European home attendance: 12,021 against Dundalk in the 1982–83 European Cup[118]

tag: ul

text: By season[edit]

text: Key

text:
P = Played
W = Games won
D = Games drawn
L = Games lost
F = Goals for
A = Goals against
GD = Goal difference
Grp = Group stage

R1 = First round
R2 = Second round
R3 = Third round
R4 = Fourth round
R16 = Round of 16
R32 = Round of 32
QF = Quarter-final
SF = Semi-final

Key to colours:

Gold
Winners

Silver
Runners-up

tag: table

text:
Liverpool F.C. record in European football by season[120][121][122]

Season

Competition

P

W

D

L

F

A

Round

1964–65

European Cup

9

5

3

1

18

5

SF

1965–66

European Cup Winners' Cup

9

5

1

3

12

6

Runners-up

1966–67

European Cup

4

1

1

2

6

8

R2

1967–68

Inter-Cities Fairs Cup

6

3

0

3

13

5

R3

1968–69

Inter-Cities Fairs Cup

1

3

0

1

3

3

R1

1969–70

Inter-Cities Fairs Cup

4

3

0

1

17

3

R2

1970–71

Inter-Cities Fairs Cup

10

5

4

1

13

4

SF

1971–72

European Cup Winners' Cup

4

1

1

2

4

5

R2

1972–73

UEFA Cup

12

8

2

2

17

6

Winners

1973–74

European Cup

4

1

1

2

5

5

R2

1974–75

European Cup Winners' Cup

4

2

2

0

12

1

R2

1975–76

UEFA Cup

12

8

3

1

25

8

Winners

1976–77

European Cup

9

7

0

2

22

5

Winners

1977

European Super Cup

2

1

1

0

7

1

Winners

1977–78

European Cup

7

5

0

2

17

7

Winners

1978

European Super Cup

2

1

0

1

3

4

Runners-up

1978–79

European Cup

2

0

1

1

0

2

R1

1979–80

European Cup

2

1

0

1

2

4

R1

1980–81

European Cup

9

6

3

0

24

4

Winners

1981

Intercontinental Cup

1

0

0

1

0

3

Runners-up

1981–82

European Cup

6

4

1

1

14

6

QF

1982–83

European Cup

6

4

0

2

13

6

QF

1983–84

European Cup

9

7

2

0

16

3

Winners

1984

European Super Cup

1

0

0

1

0

2

Runners-up

1984

Intercontinental Cup

1

0

0

1

0

1

Runners-up

1984–85

European Cup

9

6

1

2

18

5

Runners-up

1991–92

UEFA Cup

8

4

0

4

16

8

QF

1992–93

UEFA Cup Winners' Cup

4

2

0

2

10

8

R2

1995–96

UEFA Cup

4

1

2

1

2

2

R2

1996–97

UEFA Cup Winners' Cup

8

6

1

1

18

9

SF

1997–98

UEFA Cup

4

1

2

1

4

5

R2

1998–99

UEFA Cup

6

2

2

2

11

5

R3

2000–01

UEFA Cup

13

8

4

1

19

9

Winners

2001

UEFA Super Cup

1

1

0

0

3

2

Winners

2001–02

UEFA Champions League

14

5

7

2

14

11

QF

2002–03

UEFA Champions League

6

2

2

2

12

8

Grp

2002–03

UEFA Cup

6

4

1

1

6

3

QF

2003–04

UEFA Cup

8

4

3

1

14

7

R4

2004–05

UEFA Champions League

15

8

3

4

14

11

Winners

2005

UEFA Super Cup

1

1

0

0

3

1

Winners

2005

FIFA Club World Cup

2

1

0

1

3

1

Runners-up

2005–06

UEFA Champions League

14

8

3

3

20

7

R16

2006–07

UEFA Champions League

15

8

4

3

23

12

Runners-up

2007–08

UEFA Champions League

14

8

3

3

34

11

SF

2008–09

UEFA Champions League

12

7

4

1

22

12

QF

2009–10

UEFA Champions League

6

2

1

3

5

7

Grp

2009–10

UEFA Europa League

8

5

0

3

14

8

SF

2010–11

UEFA Europa League

14

7

6

1

16

5

R16

2012–13

UEFA Europa League

12

7

2

3

20

13

R32

2014–15

UEFA Champions League

6

1

2

3

5

9

Grp

2014–15

UEFA Europa League

2

1

0

1

1

1

R32

2015–16

UEFA Europa League

15

6

7

2

19

13

Runners-up

2017–18

UEFA Champions League

15

9

4

2

47

19

Runners-up

text: By competition[edit]

text:
Liverpool F.C. record in European football by competition[123]

Competition

P

W

D

L

F

A

European Cup/UEFA Champions League

196

110

45

41

368

171

UEFA Cup Winners' Cup

29

16

5

8

57

29

UEFA Cup/UEFA Europa League

124

66

34

24

186

94

Inter-Cities Fairs Cup

22

12

4

6

46

15

UEFA Super Cup

7

4

1

2

16

10

Intercontinental Cup

2

0

0

2

0

4

FIFA Club World Cup

2

1

0

1

3

1

Total

382

208

89

85

677

325

text: By country[edit]

text:
Liverpool F.C. record in Continental football by country[124]

Country[a]

Pld

W

D

L

F

A

GD

Win%

 Argentina

7000100000000000000♠1

5000000000000000000♠0

5000000000000000000♠0

7000100000000000000♠1

5000000000000000000♠0

7000100000000000000♠1

−1

005000000000000000000♠0.00

 Austria

7000600000000000000♠6

7000400000000000000♠4

7000100000000000000♠1

7000100000000000000♠1

7001130000000000000♠13

7000300000000000000♠3

+10

07001666700000000000♠66.67

 Belarus

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000400000000000000♠4

5000000000000000000♠0

+4

7002100000000000000♠100.00

 Belgium

7001130000000000000♠13

7001100000000000000♠10

7000200000000000000♠2

7000100000000000000♠1

7001220000000000000♠22

7000900000000000000♠9

+13

07001769200000000000♠76.92

 Brazil

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000200000000000000♠2

5000000000000000000♠0

7000400000000000000♠4

−4

005000000000000000000♠0.00

 Bulgaria

7001100000000000000♠10

7000700000000000000♠7

7000100000000000000♠1

7000200000000000000♠2

7001200000000000000♠20

7001100000000000000♠10

+10

07001700000000000000♠70.00

 Costa Rica

7000100000000000000♠1

7000100000000000000♠1

5000000000000000000♠0

5000000000000000000♠0

7000300000000000000♠3

5000000000000000000♠0

+3

7002100000000000000♠100.00

 Cyprus

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000800000000000000♠8

7000200000000000000♠2

+6

7002100000000000000♠100.00

 Czech Republic

7000400000000000000♠4

7000300000000000000♠3

7000100000000000000♠1

5000000000000000000♠0

7000500000000000000♠5

7000200000000000000♠2

+3

07001750000000000000♠75.00

 Denmark

7000400000000000000♠4

7000200000000000000♠2

7000100000000000000♠1

7000100000000000000♠1

7000600000000000000♠6

7000100000000000000♠1

+5

07001500000000000000♠50.00

 England

7001220000000000000♠22

7000700000000000000♠7

7000900000000000000♠9

7000600000000000000♠6

7001250000000000000♠25

7001210000000000000♠21

+4

07001318200000000000♠31.82

 Finland

7001120000000000000♠12

7000900000000000000♠9

7000200000000000000♠2

7000100000000000000♠1

7001430000000000000♠43

7000700000000000000♠7

+36

07001750000000000000♠75.00

 France

7001260000000000000♠26

7001150000000000000♠15

7000200000000000000♠2

7000900000000000000♠9

7001380000000000000♠38

7001200000000000000♠20

+18

07001576900000000000♠57.69

 Germany

7001420000000000000♠42

7001210000000000000♠21

7001140000000000000♠14

7000700000000000000♠7

7001760000000000000♠76

7001370000000000000♠37

+39

07001500000000000000♠50.00

 Georgia

7000200000000000000♠2

7000100000000000000♠1

5000000000000000000♠0

7000100000000000000♠1

7000200000000000000♠2

7000400000000000000♠4

−2

07001500000000000000♠50.00

 Greece

7000800000000000000♠8

7000600000000000000♠6

7000100000000000000♠1

7000100000000000000♠1

7001180000000000000♠18

7000500000000000000♠5

+13

07001750000000000000♠75.00

 Hungary

7001100000000000000♠10

7000400000000000000♠4

7000400000000000000♠4

7000200000000000000♠2

7000700000000000000♠7

7000400000000000000♠4

+3

07001400000000000000♠40.00

 Iceland

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7001110000000000000♠11

7000100000000000000♠1

+10

7002100000000000000♠100.00

 Ireland

7000400000000000000♠4

7000400000000000000♠4

5000000000000000000♠0

5000000000000000000♠0

7001190000000000000♠19

7000100000000000000♠1

+18

7002100000000000000♠100.00

 Israel

7000200000000000000♠2

7000100000000000000♠1

7000100000000000000♠1

5000000000000000000♠0

7000300000000000000♠3

7000200000000000000♠2

+1

07001500000000000000♠50.00

 Italy

7001270000000000000♠27

7001100000000000000♠10

7000700000000000000♠7

7001100000000000000♠10

7001340000000000000♠34

7001340000000000000♠34

+0

07001370400000000000♠37.04

 Lithuania

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000500000000000000♠5

7000100000000000000♠1

+4

7002100000000000000♠100.00

 Luxembourg

7000200000000000000♠2

7000100000000000000♠1

7000100000000000000♠1

5000000000000000000♠0

7000300000000000000♠3

7000100000000000000♠1

+2

07001500000000000000♠50.00

 Macedonia

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000400000000000000♠4

5000000000000000000♠0

+4

7002100000000000000♠100.00

 Netherlands

7001140000000000000♠14

7000800000000000000♠8

7000500000000000000♠5

7000100000000000000♠1

7001220000000000000♠22

7001120000000000000♠12

+10

07001571400000000000♠57.14

 Northern Ireland

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000700000000000000♠7

5000000000000000000♠0

+7

7002100000000000000♠100.00

 Norway

7000400000000000000♠4

7000300000000000000♠3

7000100000000000000♠1

5000000000000000000♠0

7001160000000000000♠16

7000100000000000000♠1

+15

07001750000000000000♠75.00

 Poland

7000600000000000000♠6

7000500000000000000♠5

5000000000000000000♠0

7000100000000000000♠1

7001130000000000000♠13

7000500000000000000♠5

+8

07001833300000000000♠83.33

 Portugal

7001220000000000000♠22

7001100000000000000♠10

7000600000000000000♠6

7000600000000000000♠6

7001360000000000000♠36

7001190000000000000♠19

+17

07001454500000000000♠45.45

 Romania

7001150000000000000♠15

7001100000000000000♠10

7000400000000000000♠4

7000100000000000000♠1

7001240000000000000♠24

7000900000000000000♠9

+15

07001666700000000000♠66.67

 Russia

7001130000000000000♠13

7000700000000000000♠7

7000200000000000000♠2

7000400000000000000♠4

7001270000000000000♠27

7001140000000000000♠14

+13

07001538500000000000♠53.85

 Scotland

7001140000000000000♠14

7000700000000000000♠7

7000400000000000000♠4

7000300000000000000♠3

7001180000000000000♠18

7000900000000000000♠9

+9

07001500000000000000♠50.00

 Serbia

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000200000000000000♠2

7000200000000000000♠2

7000400000000000000♠4

−2

005000000000000000000♠0.00

 Slovakia

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000800000000000000♠8

5000000000000000000♠0

+8

7002100000000000000♠100.00

 Slovenia

7000400000000000000♠4

7000300000000000000♠3

7000100000000000000♠1

5000000000000000000♠0

7001140000000000000♠14

7000100000000000000♠1

+13

07001750000000000000♠75.00

 Spain

7001400000000000000♠40

7001150000000000000♠15

7001120000000000000♠12

7001130000000000000♠13

7001500000000000000♠50

7001440000000000000♠44

+6

07001375000000000000♠37.50

 Sweden

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000400000000000000♠4

7000100000000000000♠1

+3

7002100000000000000♠100.00

  Switzerland

7001130000000000000♠13

7000600000000000000♠6

7000500000000000000♠5

7000200000000000000♠2

7001290000000000000♠29

7001180000000000000♠18

+11

07001461500000000000♠46.15

 Turkey

7001120000000000000♠12

7000600000000000000♠6

7000200000000000000♠2

7000400000000000000♠4

7001220000000000000♠22

7001110000000000000♠11

+11

07001500000000000000♠50.00

 Ukraine

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000300000000000000♠3

7000100000000000000♠1

+2

7002100000000000000♠100.00

 Wales

7000200000000000000♠2

7000200000000000000♠2

5000000000000000000♠0

5000000000000000000♠0

7000600000000000000♠6

5000000000000000000♠0

+6

7002100000000000000♠100.00

text: Honours[edit]

text:
Liverpool F.C. honours in European competition

Honour

No.

Years

European Cup/UEFA Champions League

5

1977, 1978, 1981, 1984, 2005

UEFA Cup/UEFA Europa League

3

1973, 1976, 2001

UEFA Super Cup

3

1977, 2001, 2005

text: Notes[edit]

text: Jump up ^ The table excludes former nations such as East Germany and the Soviet Union.

tag: ol


document_title: Heart failure

question_text: right side failure in the heart is characterized by

question_tokens: right side failure in the heart is characterized by

text: Heart failure

text: Terminology[edit]

text: Heart failure is a physiological state in which cardiac output is insufficient to meet the needs of the body and lungs.[2] The term "congestive heart failure"  is often used, as one of the common symptoms is congestion, or build-up of fluid in a person's tissues and veins in the lungs or other parts of the body.[2] Specifically, congestion takes the form of water retention and swelling (edema), both as peripheral edema (causing swollen limbs and feet) and as pulmonary edema (causing breathing difficulty), as well as ascites (swollen abdomen). This is a common problem in old age as a result of cardiovascular disease, but it can happen at any age, even in fetuses.

text: The term "acute" is used to mean rapid onset, and "chronic" refers to long duration. Chronic heart failure is a long-term condition, usually kept stable by the treatment of symptoms. Acute decompensated heart failure is a worsening of chronic heart failure symptoms which can result in acute respiratory distress.[20] High-output heart failure can occur when there is an increased cardiac output. The circulatory overload caused, can result in an increased left ventricular diastolic pressure which can develop into pulmonary congestion (pulmonary edema).[21]

text: Heart failure is divided into two types based on ejection fraction, which is the proportion of blood pumped out of the heart during a single contraction.[22] Ejection fraction is given as a percentage with the normal range being between 50 and 75%.[22] The two types are:

text: 1) Heart failure due to reduced ejection fraction (HFrEF). This type is also known as heart failure due to left ventricular systolic dysfunction or systolic heart failure. This type of heart failure occurs when the ejection fraction is less than 40%.[23]

text: 2) Heart failure with preserved ejection fraction (HFpEF). This type is also known as diastolic heart failure or heart failure with normal ejection fraction.[2][16] This type of heart failure occurs when the heart muscle contracts well but the ventricle does not fill with blood well in the relaxation phase.[2]

text: Signs and symptoms[edit]

text: Heart failure symptoms are traditionally and somewhat arbitrarily divided into "left" and "right" sided, recognizing that the left and right ventricles of the heart supply different portions of the circulation. However, heart failure is not exclusively backward failure (in the part of the circulation which drains to the ventricle).

text: There are several other exceptions to a simple left-right division of heart failure symptoms. Additionally, the most common cause of right-sided heart failure is left-sided heart failure.[24] The result is that patients commonly present with both sets of signs and symptoms.

text: Left-sided failure[edit]

text: The left side of the heart is responsible for receiving oxygen-rich blood from the lungs and pumping it forward to the systemic circulation (the rest of the body except for the pulmonary circulation). Failure of the left side of the heart causes blood to back up  (be congested) into the lungs, causing respiratory symptoms as well as fatigue due to insufficient supply of oxygenated blood. Common respiratory signs are increased rate of breathing and increased work of breathing (non-specific signs of respiratory distress). Rales or crackles, heard initially in the lung bases, and when severe, throughout the lung fields suggest the development of pulmonary edema (fluid in the alveoli). Cyanosis which suggests severe low blood oxygen, is a late sign of extremely severe pulmonary edema.

text: Additional signs indicating left ventricular failure include a laterally displaced apex beat (which occurs if the heart is enlarged) and a gallop rhythm (additional heart sounds) may be heard as a marker of increased blood flow or increased intra-cardiac pressure. Heart murmurs may indicate the presence of valvular heart disease, either as a cause (e.g. aortic stenosis) or as a result (e.g. mitral regurgitation) of the heart failure.

text: Backward failure of the left ventricle causes congestion of the lungs' blood vessels, and so the symptoms are predominantly respiratory in nature. Backward failure can be subdivided into the failure of the left atrium, the left ventricle or both within the left circuit. The patient will have dyspnea (shortness of breath) on exertion and in severe cases, dyspnea at rest. Increasing breathlessness on lying flat, called orthopnea, occurs. It is often measured in the number of pillows required to lie comfortably, and in orthopnea, the patient may resort to sleeping while sitting up. Another symptom of heart failure is paroxysmal nocturnal dyspnea: a sudden nighttime attack of severe breathlessness, usually several hours after going to sleep. Easy fatigability and exercise intolerance are also common complaints related to respiratory compromise.

text: "Cardiac asthma" or wheezing may occur.

text: Compromise of left ventricular forward function may result in symptoms of poor systemic circulation such as dizziness, confusion and cool extremities at rest.

text: Right-sided failure[edit]

text: Right-sided heart failure is often caused by pulmonary heart disease (cor pulmonale), which is usually caused by difficulties of the pulmonary circulation, such as pulmonary hypertension or pulmonic stenosis.

text: Physical examination may reveal pitting peripheral edema, ascites, and liver enlargement. Jugular venous pressure is frequently assessed as a marker of fluid status, which can be accentuated by eliciting hepatojugular reflux. If the right ventricular pressure is increased, a parasternal heave may be present, signifying the compensatory increase in contraction strength.

text: Backward failure of the right ventricle leads to congestion of systemic capillaries. This generates excess fluid accumulation in the body. This causes swelling under the skin (termed peripheral edema or anasarca) and usually affects the dependent parts of the body first (causing foot and ankle swelling in people who are standing up, and sacral edema in people who are predominantly lying down). Nocturia (frequent nighttime urination) may occur when fluid from the legs is returned to the bloodstream while lying down at night. In progressively severe cases, ascites (fluid accumulation in the abdominal cavity causing swelling) and liver enlargement may develop. Significant liver congestion may result in impaired liver function (congestive hepatopathy), and jaundice and even coagulopathy (problems of decreased or increased blood clotting) may occur.

text: Biventricular failure[edit]

text: Dullness of the lung fields to finger percussion and reduced breath sounds at the bases of the lung may suggest the development of a pleural effusion (fluid collection between the lung and the chest wall). Though it can occur in isolated left- or right-sided heart failure, it is more common in biventricular failure because pleural veins drain into both the systemic and pulmonary venous systems. When unilateral, effusions are often right sided.

text: If a person with a failure of one ventricle lives long enough, it will tend to progress to failure of both ventricles. For example, left ventricular failure allows pulmonary edema and pulmonary hypertension to occur, which increase stress on the right ventricle. Right ventricular failure is not as deleterious to the other side, but neither is it harmless.

text: Causes[edit]

text: Congestive heart failure[edit]

text: Heart failure may also occur in situations of "high output" (termed "high-output heart failure"), where the amount of blood pumped is more than typical and the heart is unable to keep up.[21] This can occur in overload situations (blood or serum infusions), kidney diseases, chronic severe anemia, beriberi (vitamin B1/thiamine deficiency), hyperthyroidism, cirrhosis, Paget's disease, multiple myeloma, arteriovenous fistulae, or arteriovenous malformations.

text: Viral infections of the heart can lead to inflammation of the muscular layer of the heart and subsequently contribute to the development of heart failure. Heart damage can predispose a person to develop heart failure later in life and has many causes including systemic viral infections (e.g., HIV), chemotherapeutic agents such as daunorubicin, cyclophosphamide, and trastuzumab, and abuse of drugs such as alcohol, cocaine, and methamphetamine. An uncommon cause is exposure to certain toxins such as lead and cobalt. Additionally, infiltrative disorders such as amyloidosis and connective tissue diseases such as systemic lupus erythematosus have similar consequences. Obstructive sleep apnea (a condition of sleep wherein disordered breathing overlaps with obesity, hypertension, and/or diabetes) is regarded as an independent cause of heart failure.

text: Acute decompensation[edit]

text: Chronic stable heart failure may easily decompensate. This most commonly results from an intercurrent illness (such as myocardial infarction (a heart attack), pneumonia), abnormal heart rhythms, uncontrolled hypertension, or a patient's failure to maintain a fluid restriction, diet, or medication.[25] Other well recognized factors that may worsen CHF include the following: anemia and hyperthyroidism which place additional strain on the heart muscle, excessive fluid or salt intake, and medication that causes fluid retention such as NSAIDs and thiazolidinediones.[26] NSAIDs in general increase the risk twofold.[27]

text: Medications[edit]

text: A number of medications may cause or worsen the disease. This includes NSAIDS, a number of anesthetic agents such as ketamine, thiazolidinediones, a number of cancer medications, salbutamol, and tamsulosin among others.[28]

text: Pathophysiology[edit]

text: Heart failure is caused by any condition which reduces the efficiency of the heart muscle, through damage or overloading. As such, it can be caused by a wide number of conditions, including myocardial infarction (in which the heart muscle is starved of oxygen and dies), hypertension (which increases the force of contraction needed to pump blood) and amyloidosis (in which misfolded proteins are deposited in the heart muscle, causing it to stiffen). Over time these increases in workload will produce changes to the heart itself:

text: The heart of a person with heart failure may have a reduced force of contraction due to overloading of the ventricle. In a healthy heart, increased filling of the ventricle results in increased contraction force (by the Frank–Starling law of the heart) and thus a rise in cardiac output. In heart failure, this mechanism fails, as the ventricle is loaded with blood to the point where heart muscle contraction becomes less efficient. This is due to reduced ability to cross-link actin and myosin filaments in over-stretched heart muscle.[29]

text: Diagnosis[edit]

text: No system of diagnostic criteria has been agreed on as the gold standard for heart failure. The National Institute for Health and Care Excellence recommends measuring brain natriuretic peptide (BNP) followed by ultrasound of the heart if positive.[30] This is recommended in those with shortness of breath.[31] In those with heart failure who worsen both a BNP and a troponin are recommended to help determine likely outcomes.[31]

text: Ultrasound[edit]

text: Echocardiography is commonly used to support a clinical diagnosis of heart failure. This modality uses ultrasound to determine the stroke volume (SV, the amount of blood in the heart that exits the ventricles with each beat), the end-diastolic volume (EDV, the total amount of blood at the end of diastole), and the SV in proportion to the EDV, a value known as the ejection fraction (EF). In pediatrics, the shortening fraction is the preferred measure of systolic function. Normally, the EF should be between 50% and 70%; in systolic heart failure, it drops below 40%. Echocardiography can also identify valvular heart disease and assess the state of the pericardium (the connective tissue sac surrounding the heart). Echocardiography may also aid in deciding what treatments will help the patient, such as medication, insertion of an implantable cardioverter-defibrillator or cardiac resynchronization therapy. Echocardiography can also help determine if acute myocardial ischemia is the precipitating cause, and may manifest as regional wall motion abnormalities on echo.

text:
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Ultrasound showing severe systolic heart failure[32]

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Ultrasound showing severe systolic heart failure[32]

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Ultrasound of the lungs showing edema due to severe systolic heart failure[32]

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Ultrasound showing severe systolic heart failure[32]

Ultrasound showing severe systolic heart failure[32]

text: Chest X-ray[edit]

text: Chest X-rays are frequently used to aid in the diagnosis of CHF. In a person who is compensated, this may show cardiomegaly (visible enlargement of the heart), quantified as the cardiothoracic ratio (proportion of the heart size to the chest). In left ventricular failure, there may be evidence of vascular redistribution ("upper lobe blood diversion" or "cephalization"), Kerley lines, cuffing of the areas around the bronchi, and interstitial edema. Ultrasound of the lung may also be able to detect Kerley lines.[33]

text:
Congestive heart failure x-ray.

Congestive heart failure with small bilateral effusions.

Kerley b lines.

text: Electrophysiology[edit]

text: An electrocardiogram (ECG/EKG) may be used to identify arrhythmias, ischemic heart disease, right and left ventricular hypertrophy, and presence of conduction delay or abnormalities (e.g. left bundle branch block). Although these findings are not specific to the diagnosis of heart failure a normal ECG virtually excludes left ventricular systolic dysfunction.[34]

text: Blood tests[edit]

text: Blood tests routinely performed include electrolytes (sodium, potassium), measures of kidney function, liver function tests, thyroid function tests, a complete blood count, and often C-reactive protein if infection is suspected. An elevated B-type natriuretic peptide (BNP) is a specific test indicative of heart failure. Additionally, BNP can be used to differentiate between causes of dyspnea due to heart failure from other causes of dyspnea. If myocardial infarction is suspected, various cardiac markers may be used.

text: According to a meta-analysis comparing BNP and N-terminal pro-BNP (NTproBNP) in the diagnosis of heart failure, BNP is a better indicator for heart failure and left ventricular systolic dysfunction.  In groups of symptomatic patients, a diagnostic odds ratio of 27 for BNP compares with a sensitivity of 85% and specificity of 84% in detecting heart failure.[35]

text: Hyponatremia (low sodium levels) are common in heart failure. Vasopressin levels are usually increased, along with renin, angiotensin II, and catecholamines in order to compensate for reduced circulating volume due to inadequate cardiac output. This leads to increased fluid and sodium retention in the body; the rate of fluid retention is higher than the rate of sodium retention in the body, this phenomenon causes "hypervolemic hyponatremia" (low sodium concentration due to high body fluid retention). This phenomenon is more common in older women with low body mass. Severe hyponatremia can result in accumulation of fluid in the brain, causing cerebral oedema and intracranial haemorrhage.[36]

text: Angiography[edit]

text: Angiography is the X-ray imaging of blood vessels which is done by injecting contrast agents into the bloodstream through a thin plastic tube (catheter) which is placed directly in the blood vessel. X-ray images are called angiograms.[37] Heart failure may be the result of coronary artery disease, and its prognosis depends in part on the ability of the coronary arteries to supply blood to the myocardium (heart muscle). As a result, coronary catheterization may be used to identify possibilities for revascularisation through percutaneous coronary intervention or bypass surgery.

text: Monitoring[edit]

text: Various measures are often used to assess the progress of patients being treated for heart failure. These include fluid balance (calculation of fluid intake and excretion), monitoring body weight (which in the shorter term reflects fluid shifts).[38] Remote monitoring can be effective to reduce complications for people with heart failure.[39][40]

text: Classification[edit]

text: There are many different ways to categorize heart failure, including:

text:
the side of the heart involved (left heart failure versus right heart failure). Right heart failure compromises pulmonary flow to the lungs. Left heart failure compromises aortic flow to the body and brain. Mixed presentations are common; left heart failure often leads to right heart failure in the longer term.
whether the abnormality is due to insufficient contraction (systolic dysfunction), or due to insufficient relaxation of the heart (diastolic dysfunction), or to both.
whether the problem is primarily increased venous back pressure (preload), or failure to supply adequate arterial perfusion (afterload).
whether the abnormality is due to low cardiac output with high systemic vascular resistance or high cardiac output with low vascular resistance (low-output heart failure vs. high-output heart failure).
the degree of functional impairment conferred by the abnormality (as reflected in the New York Heart Association Functional Classification[41])
the degree of coexisting illness: i.e. heart failure/systemic hypertension, heart failure/pulmonary hypertension, heart failure/diabetes, heart failure/kidney failure, etc.

text: Functional classification generally relies on the New York Heart Association functional classification. The classes (I-IV) are:

text:
Class I: no limitation is experienced in any activities; there are no symptoms from ordinary activities.
Class II: slight, mild limitation of activity; the patient is comfortable at rest or with mild exertion.
Class III: marked limitation of any activity; the patient is comfortable only at rest.
Class IV: any physical activity brings on discomfort and symptoms occur at rest.

text: This score documents the severity of symptoms and can be used to assess response to treatment. While its use is widespread, the NYHA score is not very reproducible and does not reliably predict the walking distance or exercise tolerance on formal testing.[42]

text: In its 2001 guidelines the American College of Cardiology/American Heart Association working group introduced four stages of heart failure:[43]

text:
Stage A: Patients at high risk for developing HF in the future but no functional or structural heart disorder.
Stage B: a structural heart disorder but no symptoms at any stage.
Stage C: previous or current symptoms of heart failure in the context of an underlying structural heart problem, but managed with medical treatment.
Stage D: advanced disease requiring hospital-based support, a heart transplant or palliative care.

text: The ACC staging system is useful in that Stage A encompasses "pre-heart failure" – a stage where intervention with treatment can presumably prevent progression to overt symptoms. ACC Stage A does not have a corresponding NYHA class. ACC Stage B would correspond to NYHA Class I. ACC Stage C corresponds to NYHA Class II and III, while ACC Stage D overlaps with NYHA Class IV.

text: Algorithms[edit]

text: There are various algorithms for the diagnosis of heart failure. For example, the algorithm used by the Framingham Heart Study adds together criteria mainly from physical examination. In contrast, the more extensive algorithm by the European Society of Cardiology (ESC) weights the difference between supporting and opposing parameters from the medical history, physical examination, further medical tests as well as response to therapy.

text: Framingham criteria[edit]

text: By the Framingham criteria, diagnosis of congestive heart failure (heart failure with impaired pumping capability)[44] requires the simultaneous presence of at least 2 of the following major criteria or 1 major criterion in conjunction with 2 of the following minor criteria. Major criteria include an enlarged heart on a chest x-ray, an S3 gallop (a third heart sound), acute pulmonary edema, episodes of waking up from sleep gasping for air, crackles on lung auscultation, central venous pressure of more than 16 cm H2O at the right atrium, jugular vein distension, positive abdominojugular test, and weight loss of more than 4.5 kg in 5 days in response to treatment (sometimes[45] classified as a minor criterion).[46] Minor criteria include an abnormally fast heart rate of more than 120 beats per minute, nocturnal cough, difficulty breathing with physical activity, pleural effusion, a decrease in the vital capacity by one third from maximum recorded, liver enlargement, and bilateral ankle swelling.[46]

text: Minor criteria are acceptable only if they can not be attributed to another medical condition such as pulmonary hypertension, chronic lung disease, cirrhosis, ascites, or the nephrotic syndrome.[46] The Framingham Heart Study criteria are 100% sensitive and 78% specific for identifying persons with definite congestive heart failure.[46]

text: ESC algorithm[edit]

text: The ESC algorithm weights the following parameters in establishing the diagnosis of heart failure:[47]

text:
Diagnostic assessments supporting the presence of heart failure

Assessment

Diagnosis of heart failure

Supports if present
Opposes if normal or absent

Compatible symptoms
++
++

Compatible signs
++
+

Cardiac dysfunction on echocardiography
+++
+++

Response of symptoms or signs to therapy
+++
++

ECG

Normal

++

Abnormal
++
+

Dysrhythmia
+++
+

Laboratory

Elevated BNP/NT-proBNP
+++
+

Low/normal BNP/NT-proBNP
+
+++

Low blood sodium
+
+

Kidney dysfunction
+
+

Mild elevations of troponin
+
+

Chest X-ray

Pulmonary congestion
+++
+

Reduced exercise capacity
+++
++

Abnormal pulmonary function tests
+
+

Abnormal hemodynamics at rest
+++
++

+ = some importance; ++ = intermediate importance; +++ = great importance.

text: Differential diagnosis[edit]

text: There are several terms which are closely related to heart failure and may be the cause of heart failure, but should not be confused with it. Cardiac arrest and asystole refer to situations in which there is no cardiac output at all. Without urgent treatment, these result in sudden death. Myocardial infarction ("Heart attack") refers to heart muscle damage due to insufficient blood supply, usually as a result of a blocked coronary artery. Cardiomyopathy refers specifically to problems within the heart muscle, and these problems can result in heart failure. Ischemic cardiomyopathy implies that the cause of muscle damage is coronary artery disease. Dilated cardiomyopathy implies that the muscle damage has resulted in enlargement of the heart. Hypertrophic cardiomyopathy involves enlargement and thickening of the heart muscle.

text: Prevention[edit]

text: This section needs expansion. You can help by adding to it. (September 2016)

text:
A person's risk of developing heart failure is inversely related to their level of physical activity. Those who achieved at least 500 MET-minutes/week (the recommended minimum by U.S. guidelines) had lower heart failure risk than individuals who did not report exercising during their free time; the reduction in heart failure risk was even greater in those who engaged in higher levels of physical activity than the recommended minimum.[48]
Heart failure can also be prevented by lowering high blood pressure, high blood cholesterol, and controlling diabetes. Also, remaining at the right weight and reducing obesity can help. Lowering salt, alcoholic drinks, quitting smoking, and lowering sugar intake all help.[49]

text: Management[edit]

text: Treatment focuses on improving the symptoms and preventing the progression of the disease.  Reversible causes of the heart failure also need to be addressed (e.g. infection, alcohol ingestion, anemia, thyrotoxicosis, arrhythmia, hypertension). Treatments include lifestyle and pharmacological modalities, and occasionally various forms of device therapy and rarely cardiac transplantation.

text: Acute decompensation[edit]

text: In acute decompensated heart failure (ADHF), the immediate goal is to re-establish adequate perfusion and oxygen delivery to end organs. This entails ensuring that airway, breathing, and circulation are adequate.  Immediate treatments usually involve some combination of vasodilators such as nitroglycerin, diuretics such as furosemide, and possibly noninvasive positive pressure ventilation (NIPPV). Supplemental oxygen is indicated in those with oxygen saturation levels below 90% but is not recommended in those with normal oxygen levels on room air.[50]

text: Chronic management[edit]

text: The goals of treatment for people with chronic heart failure are the prolongation of life, the prevention of acute decompensation and the reduction of symptoms, allowing for greater activity.

text: Heart failure can result from a variety of conditions. In considering therapeutic options, it is important to first exclude reversible causes, including thyroid disease, anemia, chronic tachycardia, alcohol abuse, hypertension and dysfunction of one or more heart valves. Treatment of the underlying cause is usually the first approach to treating heart failure. However, in the majority of cases, either no primary cause is found or treatment of the primary cause does not restore normal heart function. In these cases, behavioral, medical and device treatment strategies exist which can provide a significant improvement in outcomes, including the relief of symptoms, exercise tolerance, and a decrease in the likelihood of hospitalization or death. Breathlessness rehabilitation for chronic obstructive pulmonary disease (COPD) and heart failure has been proposed with exercise training as a core component. Rehabilitation should also include other interventions to address shortness of breath including psychological and education needs of patients and needs of carers.[51]

text: Lifestyle[edit]

text: Behavioral modification is a primary consideration in any chronic heart failure management program, with dietary guidelines regarding fluid and salt intake being of particular importance.[52] Fluid restriction is important to reduce fluid retention in the body and to correct the hyponatremic status of the body.[36]

text: Exercise should be encouraged and tailored to suit individual capabilities. The inclusion of regular physical conditioning as part of a cardiac rehabilitation program can significantly improve quality of life and reduce the risk of hospital admission for worsening symptoms; however, there is no evidence for a reduction in mortality rates as a result of exercise.  Furthermore, it is not clear whether this evidence can be extended to people with heart failure with preserved ejection fraction (HFpEF) or to those whose exercise regimen takes place entirely at home.[53]

text: Home visits and regular monitoring at heart failure clinics reduce the need for hospitalization and improve life expectancy.[54]

text: Medication[edit]

text: First-line therapy for people with heart failure due to reduced systolic function should include angiotensin-converting enzyme (ACE) inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) if the person develops a long term cough as a side effect of the ACE-I.[55] Use of medicines from this class is associated with improved survival and quality of life in people with heart failure.[56]

text: Beta-adrenergic blocking agents (beta blockers) also form part of the first line of treatment, adding to the improvement in symptoms and mortality provided by ACE-I/ARB.[56][57] The mortality benefits of beta blockers in people with systolic dysfunction who also have atrial fibrillation (AF) is more limited than in those who do not have AF.[58] If the ejection fraction is not diminished (HFpEF), the benefits of beta blockers are more modest; a decrease in mortality has been observed but reduction in hospital admission for uncontrolled symptoms has not been observed.[59]

text: In people who are intolerant of ACE-I and ARBs or who have significant kidney dysfunction, the use of combined hydralazine and a long-acting nitrate, such as isosorbide dinitrate, is an effective alternate strategy. This regimen has been shown to reduce mortality in people with moderate heart failure.[60] It is especially beneficial in African-Americans (AA).[60] In AAs who are symptomatic, hydralazine and isosorbide dinitrate (H+I) can be added to ACE-I or ARBs.

text: In people with markedly reduced ejection fraction, the use of an aldosterone antagonist, in addition to beta blockers and ACE-I, can improve symptoms and reduce mortality.[61][62]

text: Second-line medications for CHF do not confer a mortality benefit. Digoxin is one such medication. Its narrow therapeutic window, a high degree of toxicity, and the failure of multiple trials to show a mortality benefit have reduced its role in clinical practice. It is now used in only a small number of people with refractory symptoms, who are in atrial fibrillation and/or who have chronic low blood pressure.

text: Diuretics have been a mainstay of treatment for treatment of fluid accumulation, and include diuretics classes such as loop diuretics, thiazide-like diuretic, and potassium-sparing diuretic. Although widely used, evidence on their efficacy and safety is limited, with the exception of mineralocorticoid antagonists such as spironolactone.[61][63] Mineralocorticoid antagonists in those under 75 years old appear to decrease the risk of death.[64] A recent Cochrane review found that in small studies, the use of diuretics appeared to have improved mortality in individuals with heart failure.[65] However, the extent to which these results can be extrapolated to a general population is unclear due to the small number of participants in the cited studies.[63]

text: Anemia is an independent factor in mortality in people with chronic heart failure. The treatment of anemia significantly improves quality of life for those with heart failure, often with a reduction in severity of the NYHA classification, and also improves mortality rates.[66][67] The latest European guidelines (2012) recommend screening for iron-deficient anemia and treating with parenteral iron if anemia is found.[68]

text: The decision to anticoagulate people with HF, typically with left ventricular ejection fractions <35% is debated, but generally, people with coexisting atrial fibrillation, a prior embolic event, or conditions which increase the risk of an embolic event such as amyloidosis, left ventricular noncompaction, familial dilated cardiomyopathy, or a thromboembolic event in a first-degree relative.[69]

text: Vasopressin receptor antagonist can also be used to treat heart failure. Conivaptan is the first drug approved by US Food and Drug Administration for the treatment of euvolemic hyponatremia in those with heart failure.[36] In rare cases hypertonic 3% saline together with diuretics may be used to correct hyponatremia.[36]

text: Minimally invasive therapies[edit]

text: In people with severe cardiomyopathy (left ventricular ejection fraction below 35%), or in those with recurrent VT or malignant arrhythmias, treatment with an automatic implantable cardioverter defibrillator (AICD)  is indicated to reduce the risk of severe life-threatening arrhythmias. The AICD does not improve symptoms or reduce the incidence of malignant arrhythmias but does reduce mortality from those arrhythmias, often in conjunction with antiarrhythmic medications. In people with left ventricular ejection (LVEF) below 35%, the incidence of ventricular tachycardia (VT) or sudden cardiac death is high enough to warrant AICD placement. Its use is therefore recommended in AHA/ACC guidelines.[17]

text: Cardiac contractility modulation (CCM) is a treatment for people with moderate to severe left ventricular systolic heart failure (NYHA class II–IV)  which enhances both the strength of ventricular contraction and the heart's pumping capacity. The CCM mechanism is based on stimulation of the cardiac muscle by non-excitatory electrical signals (NES), which are delivered by a pacemaker-like device. CCM is particularly suitable for the treatment of heart failure with normal QRS complex duration (120 ms or less) and has been demonstrated to improve the symptoms, quality of life and exercise tolerance.[18][70][71][72][73] CCM is approved for use in Europe, but not currently in North America.[74][75]

text: About one third of people with LVEF below 35% have markedly altered conduction to the ventricles, resulting in dyssynchronous depolarization of the right and left ventricles. This is especially problematic in people with left bundle branch block (blockage of one of the two primary conducting fiber bundles that originate at the base of the heart and carries depolarizing impulses to the left ventricle). Using a special pacing algorithm, biventricular cardiac resynchronization therapy (CRT) can initiate a normal sequence of ventricular depolarization. In people with LVEF below 35% and prolonged QRS duration on ECG (LBBB or QRS of 150 ms or more) there is an improvement in symptoms and mortality when CRT is added to standard medical therapy.[76] However, in the two-thirds of people without prolonged QRS duration, CRT may actually be harmful.[17][18][77]

text: Surgical therapies[edit]

text: People with the most severe heart failure may be candidates for ventricular assist devices (VAD). VADs have commonly been used as a bridge to heart transplantation, but have been used more recently as a destination treatment for advanced heart failure.[78]

text: In select cases, heart transplantation can be considered. While this may resolve the problems associated with heart failure, the person must generally remain on an immunosuppressive regimen to prevent rejection, which has its own significant downsides.[79]  A major limitation of this treatment option is the scarcity of hearts available for transplantation.

text: Palliative care[edit]

text: People with CHF often have significant symptoms, such as shortness of breath and chest pain. Palliative care should be initiated early in the HF trajectory, and should not be an option of last resort.[80] Palliative care can not only provide symptom management, but also assist with advanced care planning, goals of care in the case of a significant decline, and making sure the patient has a medical power of attorney and discussed his or her wishes with this individual.[81] A 2016 and 2017 review found that palliative care is associated with improved outcomes, such as quality of life, symptom burden, and satisfaction with care.[82][80]

text: Without transplantation, heart failure may not be reversible and cardiac function typically deteriorates with time.  The growing number of patients with Stage IV heart failure (intractable symptoms of fatigue, shortness of breath or chest pain at rest despite optimal medical therapy) should be considered for palliative care or hospice, according to American College of Cardiology/American Heart Association guidelines.[81]

text: Prognosis[edit]

text: Prognosis in heart failure can be assessed in multiple ways including clinical prediction rules and cardiopulmonary exercise testing. Clinical prediction rules use a composite of clinical factors such as lab tests and blood pressure to estimate prognosis. Among several clinical prediction rules for prognosticating acute heart failure, the 'EFFECT rule' slightly outperformed other rules in stratifying patients and identifying those at low risk of death during hospitalization or within 30 days.[83] Easy methods for identifying low-risk patients are:

text:
ADHERE Tree rule indicates that patients with blood urea nitrogen < 43 mg/dl and systolic blood pressure at least 115 mm Hg have less than 10% chance of inpatient death or complications.
BWH rule indicates that patients with systolic blood pressure over 90 mm Hg, respiratory rate of 30 or fewer breaths per minute, serum sodium over 135 mmol/L, no new ST-T wave changes have less than 10% chance of inpatient death or complications.

text: A very important method for assessing prognosis in advanced heart failure patients is cardiopulmonary exercise testing (CPX testing). CPX testing is usually required prior to heart transplantation as an indicator of prognosis. Cardiopulmonary exercise testing involves measurement of exhaled oxygen and carbon dioxide during exercise. The peak oxygen consumption (VO2 max) is used as an indicator of prognosis. As a general rule, a VO2 max less than 12–14 cc/kg/min indicates a poor survival and suggests that the patient may be a candidate for a heart transplant. Patients with a VO2 max<10 cc/kg/min have a clearly poorer prognosis. The most recent International Society for Heart and Lung Transplantation (ISHLT) guidelines[84] also suggest two other parameters that can be used for evaluation of prognosis in advanced heart failure, the heart failure survival score and the use of a criterion of VE/VCO2 slope > 35 from the CPX test. The heart failure survival score is a score calculated using a combination of clinical predictors and the VO2 max from the cardiopulmonary exercise test.

text: Heart failure is associated with significantly reduced physical and mental health, resulting in a markedly decreased quality of life.[85][86] With the exception of heart failure caused by reversible conditions, the condition usually worsens with time. Although some people survive many years, progressive disease is associated with an overall annual mortality rate of 10%.[87]

text: Approximately 18 of every 1000 persons will experience an ischemic stroke during the first year after diagnosis of HF. As the duration of follow-up increases, the stroke rate rises to nearly 50 strokes per 1000 cases of HF by 5 years.[88]

text: Epidemiology[edit]

text: In 2015 heart failure affected about 40 million people globally.[7] Overall around 2% of adults have heart failure[19] and in those over the age of 65, this increases to 6–10%.[3][8] Above 75 years old rates are greater than 10%.[19]

text: Rates are predicted to increase.[19] Increasing rates are mostly because of increasing life span, but also because of increased risk factors (hypertension, diabetes, dyslipidemia, and obesity) and improved survival rates from other types of cardiovascular disease (myocardial infarction, valvular disease, and arrhythmias).[89][90] Heart failure is the leading cause of hospitalization in people older than 65.[91]

text: United States[edit]

text: In the United States, heart failure affects 5.8 million people, and each year 550,000 new cases are diagnosed.[92] In 2011, congestive heart failure was the most common reason for hospitalization for adults aged 85 years and older, and the second most common for adults aged 65–84 years.[93]  It is estimated that one in five adults at age 40 will develop heart failure during their remaining lifetime and about half of people who develop heart failure die within 5 years of diagnosis.[94] Heart failure is much higher in African Americans, Hispanics, Native Americans and recent immigrants from the eastern bloc countries like Russia. This high prevalence in these ethnic minority populations has been linked to high incidence of diabetes and hypertension. In many new immigrants to the U.S., the high prevalence of heart failure has largely been attributed to lack of preventive health care or substandard treatment.[95]  Nearly one out of every four patients (24.7%) hospitalized in the U.S. with congestive heart failure are readmitted within 30 days.[96] Additionally, more than 50% of people seek re-admission within 6 months after treatment and the average duration of hospital stay is 6 days.

text: Congestive heart failure is a leading cause of hospital readmissions in the U.S. People aged 65 and older were readmitted at a rate of 24.5 per 100 admissions in 2011. In the same year, Medicaid patients were readmitted at a rate of 30.4 per 100 admissions, and uninsured patients were readmitted at a rate of 16.8 per 100 admissions. These are the highest readmission rates for both patient categories. Notably, congestive heart failure was not among the top ten conditions with the most 30-day readmissions among the privately insured.[97]

text: United Kingdom[edit]

text: In the UK has despite moderate improvements in prevention, heart failure rates have increased due to population growth and ageing.[98] Overall heart failure rates are similar to the four most common causes of cancer (breast, lung, prostate and colon) combined.[98] People from deprived backgrounds are more likely to be diagnosed with heart failure and at a younger age.[98]

text: Developing world[edit]

text: In tropical countries, the most common cause of HF is valvular heart disease or some type of cardiomyopathy. As underdeveloped countries have become more affluent, there has also been an increase in the incidence of diabetes, hypertension and obesity, which have in turn raised the incidence of heart failure.[99]

text: Sex[edit]

text: Men have a higher incidence of heart failure, but the overall prevalence rate is similar in both sexes since women survive longer after the onset of heart failure.[100] Women tend to be older when diagnosed with heart failure (after menopause), they are more likely than men to have diastolic dysfunction, and seem to experience a lower overall quality of life than men after diagnosis.[100]

text: Ethnicity[edit]

text: Some sources state that people of Asian descent are at a higher risk of heart failure than other ethnic groups.[101] Other sources however have found that rates of heart failure are similar to rates found in other ethnic groups.[102]

text: Economics[edit]

text: In 2011, non-hypertensive congestive heart failure was one of the ten most expensive conditions seen during inpatient hospitalizations in the U.S., with aggregate inpatient hospital costs of more than $10.5 billion.[103]

text: Heart failure is associated with a high health expenditure, mostly because of the cost of hospitalizations; costs have been estimated to amount to 2% of the total budget of the National Health Service in the United Kingdom, and more than $35 billion in the United States.[104][105]

text: Research directions[edit]

text: There is low-quality evidence that stem cell therapy may help.[106] Although this evidence positively indicated benefit, the evidence was of lower quality than other evidence that does not indicate benefit.[107]

text: A previous claim, which came from a 2011 article published by the British Journal Heart, stated that a low salt diet increased the risk of death in those with congestive heart failure. This claim has since been withdrawn. The paper was retracted by the journal in 2013 because two of the cited studies contained duplicate data that could not be verified, and the data have since been lost.[108][109][110]

text: A 2016 Cochrane review found tentative evidence of longer life expectancy and improved left ventricular ejection fraction in persons treated with bone marrow-derived stem cells.[111]