The cardiovascular centres receive input from a series of visceral receptors with impulses traveling through visceral sensory fibers within the vagus and sympathetic nerves via the cardiac plexus. Among these receptors are various  proprioreceptors ,  baroreceptors , and  chemoreceptors , plus stimuli from the  limbic system  which normally enable the precise regulation of heart function, via cardiac reflexes. Increased physical activity results in increased rates of firing by various proprioreceptors located in muscles, joint capsules, and tendons. The cardiovascular centres monitor these increased rates of firing, suppressing parasympathetic stimulation or increasing sympathetic stimulation as needed in order to increase blood flow. [ 1 ]


Similarly, baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including pulmonary vessels and the right side of the heart itself. Rates of firing from the baroreceptors represent blood pressure, level of physical activity, and the relative distribution of blood. The cardiac centers monitor baroreceptor firing to maintain cardiac homeostasis, a mechanism called the baroreceptor reflex. With increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centers decrease sympathetic stimulation and increase parasympathetic stimulation. As pressure and stretch decrease, the rate of baroreceptor firing decreases, and the cardiac centers increase sympathetic stimulation and decrease parasympathetic stimulation. [ 1 ]


There is a similar reflex, called the atrial reflex or  Bainbridge reflex , associated with varying rates of blood flow to the atria. Increased venous return stretches the walls of the atria where specialized baroreceptors are located. However, as the atrial baroreceptors increase their rate of firing and as they stretch due to the increased blood pressure, the cardiac center responds by increasing sympathetic stimulation and inhibiting parasympathetic stimulation to increase HR. The opposite is also true. [ 1 ]


In addition to the  autonomic nervous system , other factors can affect this. These include epinephrine, norepinephrine, and thyroid hormones; levels of various ions including calcium, potassium, and sodium; body temperature; hypoxia; and pH balance . [ 1 ]


Factors that increase heart rate also trigger an increase in stroke volume. As with skeletal muscles the heart can increase in size and efficiency with exercise. [ 1 ]  Thus endurance athletes such as  marathon runners  may have a heart that has  hypertrophied  by up to 40%. [ 3 ] : 1063–64   The difference between maximum and minimum cardiac outputs is known as the cardiac reserve and this measures the residual capacity to pump blood. [ 1 ]  Heart rates may reach up to 185–195 in exercise, depending on how fit a person is. [ 3 ]


Cardiac output (CO) is a measurement of the amount of blood pumped by each ventricle (stroke volume, SV) in one minute. To calculate this, multiply stroke volume (SV), by heart rate (HR), in  beats per minute . [ 1 ]  It can be represented by the equation: CO = HR x SV [ 1 ]


SV is normally measured using an  echocardiogram  to record end diastolic volume (EDV) and end systolic volume (ESV), and calculating the difference: SV = EDV – ESV. SV can also be measured using a specialized catheter, but this is an invasive procedure and far more dangerous to the patient. A mean SV for a resting 70-kg (150-lb) individual would be approximately 70 mL. There are several important variables, including size of the heart, physical and mental condition of the individual, sex, contractility, duration of contraction, preload or EDV, and afterload or resistance. Normal range for SV would be 55–100 mL. An average resting HR would be approximately 75 bpm but could range from 60 to 100 in some individuals. [ 1 ]  Using these numbers, (which refer to each ventricle, not both) the mean CO is 5.25 L/min, with a range of 4.0–8.0 L/min. [ 1 ]


SVs are also used to calculate ejection fraction, which is the portion of the blood that is pumped or ejected from the heart with each contraction. To calculate ejection fraction, SV is divided by EDV. Despite the name, the ejection fraction is normally expressed as a percentage. Ejection fractions range from approximately 55–70 percent, with a mean of 58 percent. [ 1 ]


Many of the factors that regulate the heart rate also affect cardiac function by altering the  stroke volume . While a number of variables are involved, stroke volume is dependent upon the difference between end diastolic volume and end systolic volume. The three primary factors involved are  preload ,  afterload  and  contractility . [ 1 ]


Preload  is another way of expressing EDV. Therefore, the greater the EDV, the greater the preload. A main factor is ventricular filling time. The faster the contractions are, the shorter the filling time and both the EDV and preload are lower. [ 1 ]


The relationship between ventricular stretch and contraction has been stated in the  Frank-Starling mechanism  which says that the force of contraction is directly proportional to the initial length of muscle fibre. So that the greater the stretch of the ventricle the greater the contraction. Any sympathetic stimulation to the venous system will increase venous return to the heart and ventricular filling. [ 1 ]


The ventricles must develop a certain tension to pump blood against the resistance of the vascular system. This tension is called  afterload . When the resistance is increased particularly due to  stenotic  valve damage the afterload must necessarily increase. A decrease in normal vascular resistance can also occur. Different cardiac responses operate to restore homeostasis of the pressure and blood flow. [ 1 ]


The ability of the myocardium to contract, (its  contractility ), controls the stroke volume which determines the end systolic volume. The greater the contraction the greater the stroke volume and the smaller the end systolic volume. Positive or negative  inotropic factors  via sympathetic and parasympathetic stimulation respectively, can increase or decrease the force of contractions. Sympathetic stimulation triggers the release of norepinephrine from the cardiac nerves and also stimulates the  adrenal cortex  to secrete both epinephrine and norepinephrine. These secretions increase the heart rate, subsequent metabolic rate and contractility. Parasympathetic stimulation stimulates the release of  acetylcholine  (ACh) from the  vagus nerve  which decreases contractility, and stroke volume which increases end systolic volume. [ citation needed ]


Several synthetic drugs have been developed that can act either as a stimulant or inhibitor inotrope. The stimulant inotropes, such as  Digoxin , cause higher concentrations of calcium ions which increase contractility. Excess calcium ( hypercalcemia ) is also a positive inotrope. Drugs that are negative inotropes include  beta blockers  and  calcium channel blockers .  Hypoxia ,  acidosis ,  hyperkalemia  are also negative inotropic agents. [ citation needed ]


The  cardiac plexus  is a  plexus  of nerves situated at the base of the  heart  that innervates the heart.


The cardiac plexus is divided into a superficial part, which lies in the concavity of the  aortic arch , and a deep part, between the aortic arch and the  trachea . The two parts are, however, closely connected. The  sympathetic  component of the cardiac plexus comes from  cardiac nerves , which originate from the sympathetic trunk. The  parasympathetic  component of the cardiac plexus originates from the  cardiac branches of the vagus nerve .


The superficial part of the cardiac plexus lies beneath the  aortic arch , in front of the  right pulmonary artery . It is formed by the superior cervical cardiac branch of the left  sympathetic trunk  and the inferior cardiac branch of the left  vagus nerve . [ 1 ]  A small ganglion, the  cardiac ganglion of Wrisberg , is occasionally found connected with these nerves at their point of junction. This ganglion, when present, is situated immediately beneath the arch of the aorta, on the right side of the  ligamentum arteriosum .


The superficial part of the cardiac plexus gives branches to:


The deep part of the cardiac plexus is situated in front of the bifurcation of the  trachea  (known as the  carina ), above the point of division of the pulmonary artery, and behind the aortic arch. It is formed by the cardiac nerves derived from the cervical ganglia of the sympathetic trunk, and the cardiac branches of the vagus and  recurrent laryngeal nerves .


The only cardiac nerves which do not enter into the formation of the deep part of the cardiac plexus are the superior cardiac nerve of the left sympathetic trunk, and the lower of the two superior cervical cardiac branches from the left vagus nerve, which pass to the superficial part of the plexus.


The branches from the right half of the deep part of the cardiac plexus pass, some in front of, and others behind, the right pulmonary artery; the former, the more numerous, transmit a few filaments to the anterior pulmonary plexus, and are then continued onward to form part of the anterior coronary plexus; those behind the pulmonary artery distribute a few filaments to the right atrium, and are then continued onward to form part of the posterior coronary plexus.


The left half of the deep part of the plexus is connected with the superficial part of the cardiac plexus, and gives filaments to the left atrium, and to the anterior pulmonary plexus, and is then continued to form the greater part of the posterior coronary plexus.


This article incorporates text in the  public domain  from  page 984  of the 20th edition of   Gray's Anatomy   (1918)


According to the  cardiocentric hypothesis , the heart is the primary location of human emotions, cognition, and awareness. [ 1 ]  This notion may be traced back to ancient civilizations such as  Egypt  and  Greece , where the heart was regarded not only as a physical organ but also as a repository of emotions and wisdom. [ 2 ]   Aristotle , a well-known Greek philosopher in this field, contributed to the notion by thinking the heart to be the centre of both emotions and intellect. He believed that the heart was the center of the psycho-physiological system and that it was responsible for controlling sensation, thought, and body movement. He also observed that the heart was the origin of the veins in the body and that the existence of  pneuma  in the heart was to function as a messenger, traveling through blood vessels to produce sensation. [ 3 ]  This point of view remained throughout history, spanning the  Middle Ages  and  Renaissance , influencing medical and intellectual debate. [ 2 ]


An opposing theory called "cephalocentrism", which proposed that the  brain  played the dominant role in controlling the body, was first introduced by  Pythagoras  in 550 BC, who argued that the soul resides in the brain and is immortal. [ 4 ]  His statements were supported by  Plato ,  Hippocrates , and  Galen of Pergamon . Plato believed that the body is a "prison" of the mind and soul and that in death the mind and soul become separated from the body, meaning that neither one of them could die. [ 5 ]


In  ancient Egypt , people believed that the heart is the seat of the soul and the origin of the channels to all other parts of the body, including  arteries ,  veins ,  nerves , and  tendons . The heart was also depicted as determining the fate of ancient Egyptians after they died. It was believed that  Anubis , the god of  mummification , would weigh the deceased person's heart against a feather. If the heart was too heavy, it would be considered guilty and consumed by the  Ammit , a mythological creature. If it was lighter than the feather, the spirit of the deceased would be allowed to go to  heaven . Therefore, the heart was kept in the mummy while other organs were generally removed. [ 6 ]


However, the  ancient Greeks ,  Aristotle  promoted the cardiocentric hypothesis based on his experience with animal dissection. [ 7 ]  He found that certain primitive animals could move and feel without the brain, and so deduced that the brain was not responsible for movement or feeling. Apart from that, he pointed out that the brain was at the top of the body, far from the centre of the body, and felt cold. He also performed anatomical examinations after strangling the specimen, which would cause  vasoconstriction  of the  arterioles  in the  lungs . This likely had the effect of forcing blood to engorge the veins and make them more visible in the following dissection. Aristotle observed that the heart was the origin of the veins in the body, and concluded that the heart was the centre of the psycho-physiological system. He also stated that the existence of  pneuma  in the heart was to function as a messenger, traveling through blood vessels to produce sensation. Movement of body parts was thought to be controlled by the heart as well. From Aristotle's perspective, the heart was composed of  sinews  which allowed the body to move. [ 8 ]


In the fourth century BC,  Diocles of Carystus  reasserted that the heart was the physiological centre of sensation and thought. He also recognised that the heart had two cardiac ears. Although Diocles also proposed that the  left brain  was responsible for intelligence and the  right one  was for sensation, he believed that the heart was dominant over the brain for listening and understanding. [ 9 ]   Praxagoras of Cos  was a follower of Aristotle's cardiocentric theory and was the first one to distinguish arteries and veins. He conjectured that arteries carry pneuma while transporting blood. [ clarification needed ]  He also proved that a  pulse  can be detected from the arteries and explained that the arteries' ends narrowed into nerves. [ 10 ]


Lucretius  stated around 55 BCE, "The dominant force in the whole body is that guiding principle which we term mind or intellect. This is firmly lodged in the midregion of the breast. Here is the place where fear and alarm pulsate. Here is felt the caressing touch of joy. Here, then, is the seat of the intellect and the mind." [ 11 ] [ 12 ]


Cardiocentrism is accepted in the  Quran . [ 13 ]  The Islamic philosopher and physician  Avicenna  followed  Galen of Pergamon , believing that one's spirit was confined in three chambers of the brain and accepted that nerves originate from the brain and  spinal cord , which control body movement and sensation. However, he maintained the earlier cardiocentric hypothesis. He stated that activation for voluntary movement began in the heart and was then transported to the brain. Similarly, messages were delivered from a peripheral environment to the brain and then via the  vagus nerve  to the heart. [ citation needed ]


In the Middle Ages, the German Catholic friar  Albertus Magnus  made contributions to physiology and biology. His treatise was based on Galen's cephalocentric theory and was profoundly affected by Avicenna's preeminent Canon, which itself had been influenced by Aristotle. He combined these ideas in a new way which suggested that nerves branched off from the brain but that the origin was the heart. He concluded that philosophically, all matters originated from the heart, and in the corporeal explanation, all nerves started from the brain. [ citation needed ]


William Harvey , an early modern English physiologist, also agreed with Aristotle's cardiocentric view. He was the first to describe the basic operation of the circulatory system, by which blood was pumped by the heart to the rest of the body, in detail. He explained that the heart was the centre of the body and the source of life in his treatise  De Motu Cordis et Sanguinis in Animalibus .


Hippocrates of Kos was the first to suggest that the brain was the seat of the soul and intelligence. From his treatise  De morbo sacro , he pointed out that the brain controls the rest of the body and is responsible for sensation and understanding. Apart from that, he believed that all feelings originated from the brain.


Galen of Pergamon was a biologist and physician. His approach to the investigation of the brain was due to his rigorous anatomical methodology. He pointed out that only correct dissection will support the incontrovertible statement. He reached the conclusion that the brain was responsible for sensation and thought, and that nerves originated at the spinal cord and brain. [ 14 ]


The "little brain in the heart" is an intricate system of nerve cells that control and regulate the heart's activity. It is also called the intrinsic cardiac nervous system (ICNS). [ 15 ]  It consists of about 40,000 neurons that form clusters or ganglia around the heart, especially near the top where the blood vessels enter and exit. These neurons communicate with each other and with the brain through chemical and electrical signals. [ 16 ]


The intrinsic cardiac nervous system has several functions, such as:


Cardioprotection   includes all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage. [ 1 ]  Cardioprotection encompasses several regimens that have shown to preserve function and viability of  cardiac muscle  cell tissue subjected to  ischemic insult  or  reoxygenation . Cardioprotection includes strategies that are implemented before an  ischemic event  ( preconditioning , PC), during an ischemic event (perconditioning, PerC) and after the event and during reperfusion (postconditioning, PostC). [ 2 ]  These strategies can be further stratified by performing the intervention locally or remotely, creating classes of conditioning known as remote  ischemic PC  (RIPC), remote ischemic PostC and remote ischemic PerC. [ 2 ]  Classical (local)  preconditioning  has an early phase with an immediate onset lasting 2–3 hours that protects against  myocardial infarction . [ 3 ]  The early phase involves  post-translational modification  of preexisting proteins, brought about by the activation of  G protein-coupled receptors  as well as downstream  MAPK's  and  PI3/Akt . These signaling events act on the  ROS -generating  mitochondria , activate  PKCε  and the Reperfusion Injury Salvage Kinase (RISK) pathway, preventing  mitochondrial permeability transition pore  (MTP) opening. [ 4 ]  The late phase with an onset of 12–24 hours that lasts 3–4 days and protects against both infarction and reversible postischemic contractile dysfunction, termed  myocardial stunning . [ 5 ] [ 6 ] [ 7 ]  This phase involves the synthesis of new cardioprotective  proteins  stimulated by  nitric oxide  (NO),  ROS  and  adenosine  acting on kinases such as  PKCε  and  Src , which in turn activate  gene transcription  and upregulation of late PC molecular players (e.g.,  antioxidant  enzymes,  iNOS ). [ 8 ]


A role for PKCε in more contemporary cardioprotection strategies including RIPC, [ 9 ]  local PostC, [ 10 ]  and remote PostC [ 11 ]  have been either demonstrated or suggested. It was shown that PKCε translocates from the  cytosolic  to the particulate fraction upon RIPC induction and that the protection conferred by RIPC can be inhibited with the PKC inhibitor  chelerythrine [ 12 ] [ 13 ]  Similarly, in models of local PostC,  phosphorylation  and activation of PKCε has been shown to be induced and PKCε inhibition attenuated the beneficial effects of these regimens. [ 14 ] [ 15 ]  A recent study showed that blocking  Hsp90  function with  geldanamycin  inhibits PostC protection and PKCε translocation. [ 16 ]  Additional studies are required to investigate a role for PKCε in remote PostC and PerC, as this has not been conclusively demonstrated.


Cardiovascular physiology  is the study of the  cardiovascular system , specifically addressing the  physiology  of the  heart  ("cardio") and  blood vessels  ("vascular").


These subjects are sometimes addressed separately, under the names  cardiac physiology  and  circulatory physiology . [ 1 ]


Although the different aspects of cardiovascular physiology are closely interrelated, the subject is still usually divided into several subtopics. [ citation needed ]


Under most circumstances, the body attempts to maintain a steady  mean arterial pressure . [ 2 ]


When there is a major and immediate decrease (such as that due to  hemorrhage  or  standing up ), the body can increase the following:


In turn, this can have a significant impact upon several other variables:


The  heart of Frédéric Chopin  was separated from his body after he died in  Paris , France, on 17 October 1849, aged 39. The Polish composer  Frédéric Chopin  had a fear of being  buried alive  and requested that his physician  Jean Cruveilhier  perform an autopsy. While Chopin's body was buried at the  Père Lachaise Cemetery  in Paris, his heart was immersed in alcohol (probably  cognac ) and placed in an oak container.


Before his death, one of Chopin's last requests was that his eldest sister,  Ludwika Jędrzejewicz , take his heart to Poland to be buried at a local church. She complied with his wishes, smuggling his heart through customs at the Austrian border, past Russian border agents and into Poland. It was given to the  Holy Cross Church  in  Warsaw  and kept in the catacombs. After a local journalist discovered the heart in a box, it was transferred to the upper part of the church in 1879 and immured in a pillar.


During the  Warsaw Uprising  in 1944, Chopin's heart was taken from the church by Nazi officials to the headquarters of  SS  commander  Erich von dem Bach-Zelewski . It was later returned to the Polish people and sent to  Milanówek  for safekeeping. On 17 October 1945, a delegation transported the heart back to Warsaw, where it was returned to its place in the Holy Cross Church.


Speculation as to the reason for Chopin's premature death led to requests by scholars and scientists to conduct an analysis of the heart tissue. While he was said to have died from  tuberculosis , it was speculated that he may have had  cystic fibrosis . A request to sample the heart tissue was refused by the Polish government, but the heart's container was secretly removed from the pillar for a visual inspection in 2014. [ 1 ]


Composer  Frédéric Chopin  had poor health throughout his life. He suffered from respiratory problems, chronic diarrhea, and weight loss. [ 2 ]  As an adult, he weighed less than 45 kilograms (99 lb). [ 3 ]  In 1849, knowing that he would soon die, Chopin made arrangements for his funeral. He had a fear of being  buried alive  ( taphophobia ) and requested to his sister that his heart be removed from his body and taken to Warsaw to be buried at a local church. [ 4 ] [ 5 ]


Chopin died in Paris on 17 October 1849. On the day before his death, Chopin requested that his physician,  Jean Cruveilhier , conduct an autopsy. During the autopsy, Cruveilhier removed Chopin's heart and submerged it in alcohol, probably  cognac . [ 6 ]  His body was buried in Paris at the  Père Lachaise Cemetery , while his heart was placed in a crystal jar that was hermetically sealed. Months later, in early 1850, his sister transported the heart to Poland. [ 7 ]  The heart would eventually come to be treated as an exceptional artefact within the  culture of Poland , afforded the respect usually reserved for saintly relics. [ 8 ]


In early January 1850, Chopin's eldest sister,  Ludwika Jędrzejewicz , returned from France by rail to Poland with her daughter and her brother's heart. She carried the heart with her, concealing its container underneath her cloak or skirt [ 6 ]  as she smuggled it through a customs inspection at the Austrian border and past Russian border agents into Poland. [ 4 ]  Soviet music historian  Igor Boelza  wrote about her journey, explaining that Jędrzejewicz had hidden "a small oak trunk under her dress. In it was a casket made of ebony wood, containing a precious vessel holding Chopin's heart". [ 5 ]


Chopin's heart arrived in Warsaw and was kept by his sister and mother, resting on top of a dresser at the home of Jędrzejewicz and the Kalasanty family. [ 5 ]  Prior to Jędrzejewicz's death in 1855, she may have arranged for the transfer of the heart to Warsaw's  Holy Cross Church . There was opposition within the church's clergy to having the heart in the upper part of the church, as Chopin was not a saint. [ 5 ]  Instead, the heart was tucked away in the church's catacombs and lay there undisturbed and unlabeled for over two decades. In 1878, journalist Adam Pług found the heart in a box and wrote about his discovery in a Warsaw journal. [ 9 ]


The clergy of the church were persuaded to move the heart in part due to the fact that the heart of novelist  Klementyna Hoffmanowa  was being kept in the  Wawel Cathedral . With the support of apostolic administrator  Antoni Ksawery Sotkiewicz , the heart was moved to the upper part of the church on 1 March 1879 and immured in the first pillar on the left, facing towards the church's great  nave . The transfer of the heart took place in secret due to fears that Tsarist authorities would seize it. Composer  Władysław Żeleński  was one of the organizers of the transfer ceremony, which was attended by around a dozen people. [ 5 ] [ 4 ]


On 29 February 1880, Chopin's heart was consecrated. A tablet carved from  Carrara marble  by sculptor  Leonard Marconi  and dedicated to the memory of Chopin was installed on the pillar a week later. A biblical verse from  Matthew 6:21  was inscribed onto one of the plaques: "For where your treasure is, there your heart will be also." [ 5 ] [ 9 ]


For decades, the heart was the sole public monument in Warsaw honoring Chopin that the Tsarist authorities allowed. It drew "covert displays of nationalist fervor". Once  Poland achieved independence  in 1918, it became an open shrine. [ 7 ]  In 1926, Archbishop Antoni Szlagowski said of Chopin: "All our past sings in him, all our slavery cries in him, the beating heart of the nation, the great king of sorrows." [ 7 ]


After the German Army  captured Warsaw  in 1939, performances of Chopin's music were banned, the  Fryderyk Chopin Institute  was shuttered, and the  Frédéric Chopin Monument  in Łazienki Park was destroyed. [ 5 ]  During the 1944  Warsaw Uprising , the Holy Cross Church was damaged and captured by the Nazis. A German priest by the name of Schulze requested that the occupying forces be allowed to take possession of Chopin's heart for safekeeping. It was taken by  SS  officer  Heinz Reinefarth [ 7 ]  and then given to SS commander  Erich von dem Bach-Zelewski , who kept it at his headquarters as part of his collection of curios. [ 4 ]


As the occupation was drawing to a close, Bach-Zelewski, known for his  brutal suppression of the uprising , returned the heart. Polish journalist  Andrzej Pettyn  [ pl ] , who wrote a definitive account of Chopin's heart, [ 5 ]  wrote that Bach-Zelewski's gesture "aimed at reducing his own fault and presenting himself to the world in a more favorable light." [ 7 ]  Bach-Zelewski ordered that Chopin's heart be transferred to the   auxiliary bishop of Warsaw   Antoni Szlagowski  [ pl ] . German officials arranged for a film crew to document the transfer of the heart to Szlagowski as a part of  Nazi propaganda . At the moment the urn containing the heart was to be handed over, the spotlights they were using malfunctioned, an event for which Szlagowski said to his colleagues: "Thank the Lord. This time these barbarians will not succeed in their propaganda ploy." [ 7 ]  Szlagowski had the heart transferred to St. Hedwig Church in  Milanówek , escorted by a contingent of German soldiers. [ 9 ]


Upon the arrival of Chopin's heart in Milanówek, it was hidden out of fear that the Germans would try to repossess it. The heart was briefly kept at the house of a professor named Antoniewicz and the apartment of the pianist Maria Findeisen. Thereafter, the heart was kept by Archbishop Szlagowski, atop a piano, in his private chapel until October 1945. A small wooden casket was created to hold the urn.  Bronisław Edward Sydow  [ pl ] , a member of the board of the Fryderyk Chopin Institute, approached officials from the  Provisional Government of National Unity  to arrange a ceremonial return of the heart to the Holy Cross Church, which by that time had been mostly restored. The Executive Committee of the National Celebration of the Return of Chopin's Heart to Warsaw was established on 18 September 1945. [ 5 ]  Sydow asked to check the condition of the relic and examined the heart in Milanówek. The container was opened and Sydow observed:


The urn consisted of an outer box made of oak, smooth, on a dark bylaid, in which there is a second mahogany box polished with  marquetry  (porte lines) embellished. Recessed in the lid is a silver plate in the form of a heart, with an engraved inscription containing Frederic Chopin's birth and death dates. This box is surrounded by lead plates for protection from moisture. Inside this box is a large crystal jar hermetically sealed, in which, in transparent alcohol, is Chopin's perfectly preserved heart. What is striking is the size of the heart, for a figure of average height it is immeasurably large. Presumably under the influence of heart disease, which primarily contributed to Chopin's early death, in addition to tuberculosis. [ 5 ]


On 17 October 1945, the 96th anniversary of Chopin's death, the urn containing his heart was handed over to Leopold Petrzyk in Milanówek in St. Hedwig Church's courtyard. A delegation including pianist  Bolesław Woytowicz  then transported it by car to  Żelazowa Wola , the village where Chopin was born, via a meandering 90-kilometre (56 mi) route taking it through  Grodzisk Mazowiecki  and Błonie. Crowds lined up along the route, which was adorned with white and red Polish flags. [ 5 ] [ 7 ]  Petrzyk passed the urn along to then-President  Bolesław Bierut , who handed it over to Warsaw mayor  Stanisław Tołwiński  [ pl ] . Following a short concert by pianist  Henryk Sztompka  [ pl ] , the delegation proceeded to Warsaw. There,  Wiktor Grodzicki  [ pl ]  gave a welcoming speech, saying in part:


This heart first beat 135 years ago, in nearby Żelazowa Wola, and soon began to beat more vividly to the sound of a folk song resounding from peasant huts, and when not many years had passed, the same peasant, Masurian song, amplified a thousandfold by Chopin's heart and genius, was already resounding throughout Europe, and today, 96 years after that heart stopped beating – it resounds throughout the world, bearing witness to the immortal values of our song, our culture and our nation. [ 5 ]


After the heart arrived in Warsaw, an afternoon commemorative service at Holy Cross Church was broadcast to the nation, with both the president and the prime minister of Poland in attendance. [ 9 ]  A eulogy given by musicology professor  Hieronim Feicht  [ pl ]  was described by the newspaper  Życie Warszawy  as "a profound analysis of the artistic values of Chopin's music". The heart was then returned to the pillar beneath a bust of Chopin created by sculptor  Andrzej Pruszyński  [ pl ] . [ 5 ]


Over the years, speculation about the cause of Chopin's death led to calls to examine the heart. In 2008, scholars requested that a  DNA analysis  of the heart's tissue be conducted to determine if Chopin had died from  cystic fibrosis  rather than tuberculosis. Cystic fibrosis was unknown during his lifetime and was thought to be a better explanation for his symptoms. [ 7 ]  The request was refused by the Polish government. [ 10 ]


On 14 April 2014, a group of church officials, scientists and representatives from the  Fryderyk Chopin Institute  disinterred the jar containing Chopin's heart. Researchers examined the heart in secret, though they limited themselves to a visual inspection and did not open the jar. They took photographs, applied sealing wax to the jar, and only revealed that they had made an inspection five months later. [ 4 ]


The scientists published their findings in a 2017 article in  The American Journal of Medicine . They wrote that the floppy and massively engorged heart appeared to have been removed using the "French method"—pulling it out and severing the  aorta  and  pulmonary artery . The surface of the heart had a frosted appearance, being covered with a "fine, whitish, massive fibrillary coating". Hemorrhagic effusions were observed, as were three small white-glass nodules. The authors of the article concluded that Chopin had  pericarditis  which was brought on by tuberculosis. [ 11 ]  A letter to the editor published in the  American Journal of Medicine  called the diagnosis of tuberculosis into question. [ 12 ]


Another inspection of the heart is not expected to take place until 2064. [ 9 ]


52°14′19.3″N   21°1′01.1″E  /  52.238694°N 21.016972°E  /  52.238694; 21.016972


The  crista terminalis  (also known as the  terminal crest , [ citation needed ]  or  crista terminalis of  His [ 1 ] ) is a vertical ridge on the [ 2 ] : 56   posterolateral [ 3 ]  inner surface of the adult  right atrium  extending between the  superior vena cava , and the  inferior vena cava . [ 2 ] : 56   The crista terminalis denotes where the junction of the embryologic  sinus venosus  and the right atrium occurred during  embryonic development . [ 3 ]  It forms a boundary between the rough [ 2 ] : 56   trabecular [ 4 ]  portion and  the smooth, sinus venosus-derived portion (sinus venarum)  of the internal surface of the right atrium. The  sinoatrial node  is located within the crista terminalis. [ 2 ] : 56


The crista terminalis generally takes the form of a smooth-surfaced, crescent-shaped thickened portion of heart muscle at the opening into the right atrial appendage. [ citation needed ]  It consists of fibromuscular tissue. [ 3 ]


On the external aspect of the right atrium, corresponding to the crista terminalis, is a groove - the  terminal sulcus . [ citation needed ]


The crista terminalis provides the origin for the  pectinate muscles . [ citation needed ]


The  sinoatrial node  is located in the superior part of the crista terminalis at the junction of the right atrium, and  superior vena cava . [ 2 ] : 60


During the development of the human heart, the right horn and transverse portion of the  sinus venosus  ultimately become incorporated with and form a part of the adult  right atrium . [ 1 ]  The right sinus horn [ 4 ]  of the sinus venosus develops into the  sinus venarum ; in the adult right atrium, the portion of right atrium derived from the sinus venosus has a smooth inner surface. [ 2 ] : 56


A prominent crista terminalis may be mistaken for a cardiac mass during heart imaging; a prominent crista terminalis appears as a hyperechoic ridge on  echocardiography , and homogenous to adjacent atrial wall on CT and MRI. [ 3 ]


Decellularized homografts  are  donated  human  heart valves  which have been modified via  tissue engineering . Several techniques exist for  decellularization  with the majority based on detergent or enzymatic protocols which aim to eliminate all donor cells while preserving the mechanical properties of the remaining matrix. [ 1 ]


Aortic valve  disease affects the valve between the  left ventricle  and the  aorta , and can be present as a  congenital condition  at birth or caused by other factors. Several therapeutic options are open to patients once the indication for  aortic valve replacement  has been confirmed. One option is replacement using a  mechanical valve . [ citation needed ]


This, however, necessitates a strict lifelong  anticoagulation  regime to avoid cerebral  thromboembolism . These blood thinners hold an inherent risk for severe bleeding episodes, which affects both professional and leisure activities and the majority of patients opt to not use mechanical valves for this reason. [ citation needed ]


Biological  prostheses , i.e.  pericardial heart valves  of animal origin ( xenogenic ), offer a viable alternative. However, in particular for young patients, it has been found that xenogenic valves do not provide satisfactory durability and rapid valve degeneration can occur within months. [ 2 ]


A further avenue open to patients is a so-called  Ross operation , an extensive surgical procedure in which the diseased aortic valve is replaced by the patient's  pulmonary valve  ( autograft ). The pulmonary valve then needs to be replaced by a heart valve prosthesis. A drawback of this method is that it can frequently result in a "two-valve" diseased heart, as almost all autografts are impaired by progressive dilatation in the long term, and the pulmonary valve prosthesis, often a conventional  cryopreserved   homograft , is subject to the same rate of degeneration as all biological valves. This can thereby lead to frequent reoperations [ 3 ]  which have a substantially higher mortality rate due to postoperative adhesions. [ 4 ]


The lack of durable heart valve prostheses for young patients has driven forward research in  tissue engineering  approaches for valve replacement. Current tissue-engineering concepts are based on either artificial  polymeric  or biological scaffolds, derived from donated human tissue ( allogeneic ) or animals (xenogenic). While more readily available, there have been reports of dramatic failure in the use of xenogeneic matrices in  paediatric  patients, leading to scepticism regarding their application. [ 5 ]


Total artificial tissue-engineered heart valve concepts are currently under development and would solve many unmet clinical demands, such as the permanent availability of different sizes and lengths. These concepts have shown good results in the technical implementation of valved polymeric conduit production and have successfully been used for  in vitro  and  in vivo  seeding of different (stem) cell lines. However,  preclinical  testing in long-term animal models has yet to deliver satisfactory results due to a lack of mechanical, leading to early failure of the valvular function. [ 6 ]


Aortic valve replacement using a  homograft  in orthotopic position was first performed over 50 years ago on 24 July 1962 by  Donald Ross  at  Guy's Hospital ,  London  and has been assessed in prospective randomized studies, e.g. in comparison to the Ross procedure. [ 7 ]  Aortic valve replacement using conventional  cryopreserved  homografts is currently performed only in about 3% of all patients, mostly to treat acute aortic valve  endocarditis .1 Severe  calcification  of conventional homografts frequently occurs and is the main reason for its restrictive use, however, current guidelines confirm homografts as a valid alternative for young patients requiring anatomical reconstruction of the outflow tract. [ citation needed ]


DPH have been clinically implanted since 2002 in paediatric patients. [ 8 ]  The indications mainly include patients with pulmonary diseases such as pulmonary valve stenosis, atresia or insufficiency. They have shown excellent early to midterm clinical performance, challenging conventional  cryopreserved  homografts as the "gold standard" for pulmonary valve replacement in congenital heart disease. [ 9 ] [ 10 ]  Compared to cryopreserved homograft, decellularized pulmonary homografts have shown less degeneration and had to be explanted less. [ 11 ]  The main limitation is the low availability of such homografts and the higher costs.


DAH developed at  Hannover Medical School  (MHH) have shown sufficient mechanical stability for the systemic circulation at the greatest possible extent of antigen elimination and have been validated in long-term animal models. [ 12 ]  The first DAH was implanted in human in the year 2008. [ 13 ]


A multicenter european study of aortic valve replacement with the use of DAH in 106 pediatric patients published in 2020 showed outcome data comparable to Ross procedure and mechanical aortic valve implantation and better results compared to cryopreserved homografts. In comparison to Ross procedure, early mortality rates were lower in DAH patients (2,2% versus 4,2%), however this trend was not statistically significant. Complications due to coronary reimplantation during DAH implantation occurred in 3.8% and progressive valve degeneration in 10%. [ 14 ]


A multicenter european study in both pediatric and adult patients compared DAH with Ross procedure and showed almost identical results regarding valve degeneration and freedom from explantation. [ 13 ]


The  Evans County Heart Study  was a long-term  cardiovascular  study on residents of  Evans County, Georgia . The study, which was funded by the  National Institute of Health , began in July, 1958, and was last updated as recent as May 2016. It resulted in more than 560 published papers that ultimately showed the importance of  HDL cholesterol . [ 1 ]  The study was conducted by Dr.  Curtis Gordon Hames , a  family doctor  from  Claxton, Georgia . [ 2 ]  The study took place in Evans Country because the area had a high death count due to heart complications, such as  heart disease and other cardiovascular diseases . The studies showed that there was a significant abundance of heart conditions within a variety of ethnicities. People as young as fourteen and as old as seventy-four participated in the tests, and were divided into different age groups; however only males were eligible for the study. Anyone as old as one-hundred years old could be eligible, and any younger.


The study involved 6,596 people from Evans County and 3,921 people from  Bulloch County . The study population from Evans county consisted of African-American and  Caucasian  males, ages 40–74, along with a 15-39 year old group that were involved in other studies. Then, the people were divided up into 10 random, equal in size, random samples. Also, a 50% random sample of the 15-39 year old group was taken by including people from the first five samples solely. By comprising this type of sampling, secular trends in disease patterns, along with possible aging of laboratory reagents were randomized. [ 3 ]


The study was done in Evans County, Georgia. Evans County is located in the southeastern portion of the United States. It is situated on the coastal plain estimating around 60 miles inland from the seaport of  Savannah, GA . Around half of the population lives on farms while the other half lives in meager little villages. An example is  Claxton . Claxton is a town that has a population of 2,000, about 40 percent of which is black. [ 4 ]  The white population of Evans County was large enough to provide an adequate number for the study, but the black population was considered too small and some blacks from the Bulloch county were incorporated into this study. [ 5 ]


The study can be categorized as a  cohort study  due to the longevity of the research and its focus on the residents of  Evans County, Georgia . It was the leader in the field of  epidemiology  to analyze effects and differences of  coronary heart disease  on race. [ 6 ]  The study aimed to determine how  cardiovascular disease  affected different races among a specific population. To determine the population size, a specific census was conducted in the county for the study during the first two months of 1960, recording 6,596 persons. [ 3 ]   From there, the study population included a total of 3,377 residents within Evans County. These residents included a group of randomly selected blacks and whites age 40-74 and an additional group of blacks were selected from Bulloch sub-County. A group of 15-39 year old residents were also selected into this group mainly to participate in other experiments as well. The study population was subsequently randomly divided into 10 groups. [ citation needed ]


The examination process consisted of two cardiovascular tests including "history and physical,  blood pressure  determination, standard  electrocardiogram  and chest  X-ray , and  cholesterol  determination." [ 3 ]  Ninety-two percent of the study population responded with an examination process. Therefore, data from 3,102 residents was obtained through the process. [ 7 ]


Using a prospective cohort model, the investigators sought to examine the entire population of the county aged over 40 years and half the population aged between 15 and 39 years. They ultimately achieved a 92% response rate for a total study population of 3,102 residents. From 1960 to 1962, each participant was given an initial examination in which serum cholesterol, blood pressure, weight, height and the participant's responses to a number of health behavior and medical history questions. A follow-up consisting of a similar battery of tests was completed from 1967 to 1969. For 90.9% of the study population, a physical similar to the preliminary one was completed. For another 7.9%, health status was ascertained by a phone survey of either subject or a family member. The total rate of follow-up was 98.8%. Factors assessed at the time of follow-up were systolic and diastolic blood pressure, serum cholesterol level, cigarette smoking, body weight,  hematocrit  value, ECG abnormalities and diet. Socioeconomic status was also assessed for whites, but not for blacks, as little variability was found in this factor among black subjects. [ 8 ]


A central finding of the study was that, across race and social class differences, factors associated with increased risk of  coronary heart disease  (CHD) did so equally for blacks and whites whether the risk factors were considered singly or in combination. CHD incidence remained markedly higher for white  Evans County  residents. The only  social grouping  of white residents that had equally low incidence of CHD was white  sharecroppers , which was attributed to higher rates of  physical activity  among sharecroppers when compared to whites of higher  socioeconomic status . [ 5 ]


A strength of the study was the high response rate of the population in its entirety, one of only two of its kind to successfully examine an entire community. The publication of the initial study results did not include statistical analysis. Hames attributes his decision to avoid statistical analysis to the unique design of the study. He wrote, “…it certainly is not clear to us [the investigators] what differences such tests could make in our interpretations in the context of this study… the population over 40 does not constitute a sample of some universe. They are a  universe .” [ citation needed ]


The  Framingham Heart Study  is a long-term, ongoing  cardiovascular   cohort study  of residents of the city of  Framingham ,  Massachusetts . The study began in 1948 with 5,209 adult subjects from Framingham, and is now on its third generation of participants. [ 1 ]   Prior to the study almost nothing was known about the  epidemiology  of hypertensive or  arteriosclerotic cardiovascular disease . [ 2 ]  Much of the now-common knowledge concerning heart disease, such as the effects of  diet ,  exercise , and common medications such as  aspirin , is based on this  longitudinal study . It is a project of the  National Heart, Lung, and Blood Institute , in collaboration with (since 1971)  Boston University . [ 1 ]   Various health professionals from the hospitals and universities of  Greater Boston  staff the project.


In 1948, the study was commissioned by the
 United States Congress , with multiple communities being considered for study.  The final choice was between Framingham, Massachusetts, and  Paintsville, Kentucky . Framingham was chosen when residents showed more general interest in heart research than Paintsville. Thomas Royle Dawber was director of the study from 1949 to 1966. He was appointed as chief epidemiologist shortly after the start of the project, when it was not progressing well. [ 3 ]  The study had been intended to last 20 years; however, interest grew in part due to Dr. Dawber's efforts to promote the study and engage in fundraising after he had been transferred to Boston to accept a chairmanship of preventive medicine. By 1968, it was debated whether the original study had served its purpose and should be terminated as scheduled. A committee gathered and considered that, after 20 years of research, the Framingham study should come to an end, since their hypothesis had been tested and extensive information concerning heart diseases had been gathered. Despite this conclusion, Congress failed to accept the recommendation, instead voting to continue the study. The study has been split into different segments, or "cohorts". [ citation needed ]


William P. Castelli  is a former director of the Framingham Heart Study. [ 4 ]


Over 3,000 peer-reviewed scientific papers have been published related to the Framingham Heart Study. It is generally accepted that the work is outstanding in its scope and duration, and overall is considered very useful. [ citation needed ]


It was rightly assumed from the start of the Framingham Heart Study that cardiac health can be influenced by lifestyle and environmental factors, and by inheritance. The Framingham Heart Study is the source of the term  risk factor . Before the Framingham Heart Study, doctors had little sense of heart disease prevention. In the 1950s, it was believed that clogging of arteries and narrowing of arteries ( atherosclerosis ,  arteriosclerosis ) were normal parts of aging, and that they occurred universally as people became older. High blood pressure ( hypertension ) and elevated serum cholesterol ( hypercholesterolemia ) were also seen as normal consequences of aging in the 1950s, and no treatment was available. These and further risk factors, such as  homocysteine , were gradually discovered over the years. [ 5 ] [ 6 ] [ 7 ] [ 8 ] [ 9 ]


The Framingham Heart Study, along with other important large studies, such as the  Seven Countries Study  and the  Nurses' Health Study , also showed that  healthy diet , not being  overweight  or  obese , and regular  exercise  are all important in maintaining good health, and that there are differences in cardiovascular risk between men and women. [ 10 ] [ 11 ]  Along with other important studies about smoking, such as the  British Doctors Study , it also confirmed that cigarette  smoking  is a highly significant factor in the development of heart disease, leading in many cases to  angina pectoris ,  myocardial infarction  (MI), and coronary death. [ 12 ] [ 13 ]


Recently the Framingham studies have come to be regarded as overestimating risk, particularly in the lower risk groups, such as for UK populations. [ 14 ]


One question in  evidence-based medicine  is how closely the people in a study resemble the patient with whom the health care professional is dealing. [ 15 ]


Researchers recently used contact information given by subjects over the last 30 years to map the  social network  of friends and family in the study. [ 16 ]


The 10-year  cardiovascular risk  of an individual can be estimated with the  Framingham Risk Score , including for individuals without known cardiovascular disease. The Framingham Risk Score is based on findings of the Framingham Heart Study. [ citation needed ]


Major findings from the Framingham Heart Study, according to the researchers themselves: [ 17 ]


The Framingham Heart Study participants, and their children and grandchildren, voluntarily consented to undergo a detailed  medical history ,  physical examination , and  medical tests  every three to five years, [ 21 ]  creating a wealth of data about physical and mental health, especially about cardiovascular disease. A nonprofit charity, called Friends of the Framingham Heart Study, was founded to help defray study costs and spread awareness of heart issues. Membership is limited to participants. [ citation needed ]


In recent years, scientists have been carrying out genetic research within the Framingham Heart Study.


Inheritance patterns in families, [ 22 ]  heritability and genetic correlations, [ 23 ]  molecular markers, [ 24 ]  and associations have been studied. The association studies include traditional genetic association studies, i.e., looking for associations of cardiovascular risk with gene polymorphisms ( single-nucleotide polymorphisms , SNPs) in candidate genes, and genome wide association studies (GWAS). [ 9 ]  For example, one genome wide study, called the 100 K Study, included almost 1400 participants of the Framingham Heart Study (from the original cohort, and the offspring cohort), and revealed a genetic variant associated with obesity.  The researchers were able to replicate this particular result in four other populations. [ 25 ]  Further, the SHARe Study (SNP Health Association Resource Study) uncovered new candidate genes, and confirmed already known candidate genes (for homocysteine and vitamin B12 levels) in participants of the Framingham Heart Study. [ 26 ]


Because of these exciting  genomic  results, the Framingham Heart Study has been described as "on its way to becoming the gold standard for cardiovascular genetic epidemiology". [ 27 ]


However, clinically, despite these (and other) efforts, the aggregate effect of genes on cardiovascular disease risk beyond that of traditional cardiovascular risk factors has not been established. [ 28 ]


The  Framingham Risk Score  is a sex-specific  algorithm  used to estimate the 10-year  cardiovascular risk  of an individual. The Framingham Risk Score was first developed based on data obtained from the  Framingham Heart Study , to estimate the 10-year risk of developing coronary heart disease. [ 1 ]  In order to assess the 10-year  cardiovascular disease  risk,  cerebrovascular events ,  peripheral artery disease  and  heart failure  were subsequently added as disease outcomes for the 2008 Framingham Risk Score, on top of  coronary heart disease . [ 2 ]


The Framingham Risk Score is one of a number of scoring systems used to determine an individual's chances of developing cardiovascular disease. A number of these scoring systems are available online. [ 3 ] [ 4 ]  Cardiovascular risk scoring systems give an estimate of the probability that a person will develop cardiovascular disease within a specified amount of time, usually 10 to 30 years. [ 5 ]


Because they give an indication of the risk of developing cardiovascular disease, they also indicate who is most likely to benefit from prevention. For this reason, cardiovascular risk scores are used to determine who should be offered preventive drugs such as drugs to lower blood pressure and drugs to lower cholesterol levels. [ citation needed ]


For example, nearly 30% of coronary heart disease (CHD) events in both men and women were singularly attributable to blood pressure levels that exceeded high normal (≥130/85), showing that blood pressure management and monitoring is paramount both to cardiovascular health and prediction of outcomes. [ 1 ]


Because risk scores such as the Framingham Risk Score give an indication of the likely benefits of prevention, they are useful for both the individual patient and for the clinician in helping decide whether lifestyle modification and preventive medical treatment and for patient education, by identifying men and women at increased risk for future cardiovascular events. [ 6 ]


Coronary heart disease  (CHD) risk at 10 years in percent can be calculated with the help of the Framingham Risk Score. Individuals with  low risk  have 10% or less CHD risk at 10 years, with  intermediate risk  10-20%, and with  high risk  20% or more. However, it should be remembered that  these categorisations are arbitrary . [ citation needed ]


A more useful metric is to consider the effects of treatment. If a group of 100 persons has a 20% ten-year risk of cardiovascular disease it means that we should expect that 20 of these 100 individuals will develop cardiovascular disease (coronary heart disease or stroke) in the next 10 years and eighty of them will not develop cardiovascular disease in the next 10 years. [ citation needed ]


If they were to take a combination of treatments (for example drugs to lower cholesterol levels plus drugs to lower blood pressure) that reduced their risk of cardiovascular disease by half it means that 10 of these 100 individuals should be expected to develop cardiovascular disease in the next 10 years and 90 of them should not be expected to develop cardiovascular disease. If that was the case then 10 of these individuals would have avoided cardiovascular disease by taking treatment for 10 years; 10 would get cardiovascular disease whether or not they took treatment, and 80 would not have got cardiovascular disease whether or not they took treatment. [ citation needed ]


Despite their widespread popularity, randomized trials assessing the impact of using cardiovascular disease risk scores show limited impact on patient outcomes. Although there is good evidence that targeting individuals with high total CVD risk is the most efficient way to reduce CVD-related morbidity and mortality, to date trials assessing the usefulness of risk scores at helping clinicians target high risk patients show limited benefit. [ 7 ]


It is important to recognize that the strongest predictor of cardiovascular risk in any risk equation is age. [ 8 ]


Cardiovascular disease  is common in the general population, affecting the majority of adults. It includes: [ citation needed ]


An individual's risk for future cardiovascular events is modifiable, by lifestyle changes and preventive medical treatment. Lifestyle changes can include stopping  smoking ,  healthy diet , regular  exercise , etc. Preventive medical treatment can include a  statin , mini dose  aspirin , treatment for  hypertension , etc. It is important to be able to predict the risk of an individual patient, in order to decide when to initiate lifestyle modification and preventive medical treatment. [ citation needed ]


Multiple risk models for the prediction of cardiovascular risk of individual patients have been developed. One such key  risk model  is the Framingham Risk Score. [ citation needed ]


The Framingham Risk Score is based on findings from the  Framingham Heart Study . [ citation needed ]


The Framingham Risk Score has been validated in the US, both in men and women, both in European Americans and African Americans. [ 9 ]  While several studies have claimed to improve on the FRS, there is little evidence for any improved prediction beyond the Framingham risk score  [ 10 ]


The Framingham Risk Score predicts only future coronary heart disease (CHD) events, however, it does not predict future total cardiovascular events, meaning that it does not predict risk for stroke, transient ischemic attack (TIA), and heart failure. These also important patient outcomes were included in the 2008  Framingham General Cardiovascular Risk Score . [ 2 ]  The predicted risk for an individual usually is higher with the 2008 Framingham General Cardiovascular Risk Score than with the 2002 Framingham Risk Score. [ citation needed ]


The Framingham Risk Score could overestimate (or underestimate) risk in populations other than the US population, [ 11 ] [ 12 ]  and within the US in populations other than European Americans and African Americans, e.g. Hispanic Americans and Native Americans. [ 13 ]  It is not yet clear if this limitation is real, or appears to be real because of differences in methodology, etc. As a result, other countries may prefer to use another risk score, e.g.  SCORE  (HeartScore is the interactive version of SCORE - Systematic COronary Risk Evaluation), [ 14 ]  which has been recommended by the  European Society of Cardiology  in 2007. [ 15 ]


If possible, a  cardiology  professional should select the risk prediction model which is most appropriate for an individual patient and should remember that this is only an estimate. [ citation needed ]


The current version of the Framingham Risk Score was published in 2008. The publishing body is the ATP III, i.e. the «Adult Treatment Panel III», an expert panel of the  National Heart, Lung, and Blood Institute , which is part of the  National Institutes of Health  (NIH), USA.


The prior version was published in 2002  [ 16 ]


The original Framingham Risk Score had been published in 1998. [ 1 ]


The first Framingham Risk Score included age, sex, LDL cholesterol, HDL cholesterol, blood pressure (and also whether the patient is treated or not for his/her hypertension), diabetes, and smoking. It estimated the 10-year risk for coronary heart disease (CHD). It performed well and correctly predicted a 10-year risk for CHD in American men and women of European and African descent. [ citation needed ]


The updated version was modified to include  dyslipidemia , age range, hypertension treatment, smoking, and total cholesterol, and it excluded  diabetes , because Type 2 diabetes meanwhile was considered to be a CHD Risk Equivalent, having the same 10-year risk as individuals with prior CHD. Patients with Type 1 diabetes were considered separately with slightly less aggressive goals; while at increased risk, no study had shown them to be at equivalent risk for CHD as those with previously diagnosed coronary disease or Type 2 diabetes. [ 16 ]


Some patients without known CHD have risk of cardiovascular events that is comparable to that of patients with established CHD. Cardiology professionals refer to such patients as having a CHD risk equivalent. These patients should be managed as patients with known CHD. [ citation needed ]


CHD risk equivalents are patients with a 10-year risk for  MI  or  coronary death  >20%.   CHD risk equivalents are primarily other clinical forms of atherosclerotic disease.   The   National Cholesterol Education Program  NCEP's ATP III guidelines also list diabetes as a CHD risk equivalent since it also has a 10-year risk for CHD around 20%.   NCEP ATP III CHD risk equivalents are:


The Framingham/ATP III criteria were used to estimate CHD risk in the USA. Data from 11,611 patients from a very large study, the  NHANES  III, were used. The patients were 20 to 79 years of age and had no self-reported CHD, stroke, peripheral arterial disease, or diabetes. [ citation needed ]


The results: 82% of patients had low risk (10% or less CHD risk at 10 years). 16% had intermediate risk (10-20%). 3% had high risk (20% or more). [ 23 ]


High risk was most commonly found in patients with advanced age and was more common in men than women. [ medical citation needed ]


Age : 20–34 years: Minus 7 points. 35–39 years: Minus 3 points. 40–44 years: 0 points. 45–49 years: 3 points. 50–54 years: 6 points. 55–59 years: 8 points. 60–64 years: 10 points. 65–69 years: 12 points. 70–74 years: 14 points. 75–79 years: 16 points.


Total cholesterol, mg/dL :


If cigarette smoker : Age 20–39 years: 9 points. • Age 40–49 years: 7 points. • Age 50–59 years: 4 points. • Age 60–69 years: 2 points. • Age 70–79 years: 1 point.


All non smokers : 0 points.


HDL cholesterol, mg/dL : 60 or higher: Minus 1 point. 50-59: 0 points. 40-49: 1 point. Under 40: 2 points.


Systolic blood pressure, mm Hg : Untreated: Under 120: 0 points. 120-129: 1 point. 130-139: 2 points. 140-159: 3 points. 160 or higher: 4 points. • Treated: Under 120: 0 points. 120-129: 3 points. 130-139: 4 points. 140-159: 5 points. 160 or higher: 6 points.


10-year risk in % : Points total: Under 9 points: <1%. 9-12 points: 1%. 13-14 points: 2%. 15 points: 3%. 16 points: 4%. 17 points: 5%. 18 points: 6%. 19 points: 8%. 20 points: 11%. 21=14%, 22=17%, 23=22%, 24=27%, >25= Over 30%


Age : 20–34 years: Minus 9 points. 35–39 years: Minus 4 points. 40–44 years: 0 points. 45–49 years: 3 points. 50–54 years: 6 points. 55–59 years: 8 points. 60–64 years: 10 points. 65–69 years: 11 points. 70–74 years: 12 points. 75–79 years: 13 points.


If cigarette smoker : Age 20–39 years: 8 points. • Age 40–49 years: 5 points. • Age 50–59 years: 3 points. • Age 60–69 years: 1 point. • Age 70–79 years: 1 point.


Systolic blood pressure, mm Hg : Untreated: Under 120: 0 points. 120-129: 0 points. 130-139: 1 point. 140-159: 1 point. 160 or higher: 2 points. • Treated: Under 120: 0 points. 120-129: 1 point. 130-139: 2 points. 140-159: 2 points. 160 or higher: 3 points.


10-year risk in % :
Points total:
0 point:  <1%.
1-4 points: 1%.
5-6 points: 2%.
7 points: 3%.
8 points: 4%.
9 points: 5%.
10 points: 6%.
11 points: 8%.
12 points: 10%.
13 points: 12%.
14 points: 16%.
15 points: 20%.
16 points: 25%.
17 points or more: Over 30%. [ 24 ]


Not only coronary heart disease (CHD) events but also further risks can be predicted. Risk prediction models for cardiovascular disease outcomes other than CHD events have also been developed by the Framingham Heart Study researchers. Amongst others, a risk score for 10-year risk for  atrial fibrillation  has been developed. [ 25 ] [ 26 ]


The  Giant Heart  exhibit, originally called the "Engine of Life" exhibit, is one of the most popular and notable exhibits at the  Franklin Institute . [ 1 ]  Built in 1953, the exhibit is roughly two stories tall and 35-feet in diameter. A walk-through exhibit, visitors can explore the different areas of the  heart . [ 2 ]


Visiting The Giant Heart has become a tradition or "right of passage" for many school-aged children, particularly on field trips, in the Philadelphia-area.


The original idea for the walk-through heart exhibit came from Dr. Mildred Pfeiffer, a  physician  and Director of  Cardiovascular Diseases  at the  Pennsylvania Department of Health  who would travel giving lectures about the heart and heart health; she proposed the idea of the heart in an effort to have a centralized resource that people could visit and learn of the heart. [ 3 ] [ 4 ]  The original materials used to construct the heart were  papier-mâché ,  chicken wire  and  lumber .


The Giant Heart was supposed to have only been on display for six months. [ 5 ]  It was the idea of physician Mildred Pfeiffer, who designed The Giant Heart with a medical illustrator and engineer. [ 5 ]  It was originally made out of wood, chicken wire and papier-mâché. [ 5 ]  However, The Giant Heart became a popular attraction and the Franklin Institute opted to keep it. More than 70 years later, it remains one of the most visited exhibits at The Franklin Institute. [ 5 ]


The Giant Heart is 100 times larger than the average human heart. [ 5 ]  As visitors walk-through The Giant Heart there is signage pointing out which part of the "heart" they are walking past. [ 5 ]


The deeper visitors walk deeper into the heart, the sound of a heartbeat gets louder and louder. [ 5 ]  The sound of the heartbeat was originally computer generated, but as part of the 2019 renovations, it was replaced by the sound of a real human heartbeat. [ 5 ]


Stephanie Farr writing in  The Philadelphia Inquirer  said that The Giant Heart has a "universally recognized-but-hard-to-define odor." [ 5 ]


Located next to The Giant Heart is the Bio-science exhibit, which aims to teaching and sparking interest among visitors in the science of the human body.


In 1979, The Giant Heart was rebuilt with fiberglass. [ 5 ]  The Giant Heart was remodeled and updated in 2004 and 2019. [ 6 ]


39°57′30″N   75°10′23″W  /  39.95837°N 75.17319°W  /  39.95837; -75.17319


Heart nanotechnology  is the "Engineering of functional systems at the molecular scale" ("Nanotechnology Research"). [ 1 ]


Nanotechnology  deals with structures and materials that are approximately one to one-hundred nanometers in length. At this microscopic level,  quantum mechanics  take place and are in effect, resulting in behaviors that would seem quite strange compared to what humans see with the naked eye (regular matter). Nanotechnology is used for a wide variety of fields of technology, ranging from  energy  to  electronics  to  medicine . In the category of medicine, nanotechnology is still relatively new and has not yet been widely adopted by the field. It is possible that nanotechnology could be the new breakthrough of medicine and may eventually be the solution and cure for many of the health problems that humans encounter. Nanotechnology may lead to the cure for illnesses such as the  common cold , diseases, and  cancer .  It is already starting to be used as a treatment for some serious health issues; more specifically it is being used to treat the  heart  and cancer. [ citation needed ]


Nanotechnology in the field of medicine is more commonly referred to as  nanomedicine . Nanomedicine that deals with helping the heart is really starting to take off and gain in popularity compared to most of the other fields that nanomedicine currently has to offer.  There are several heart problems that nanotechnology has promising evidence of being effective in the treatment of  heart disease  in the near future.


It should hopefully be able to treat  heart valves  that are defective; and detect and treat  arterial plaque  in the heart ("Nanotechnology Made Clear").  Nanomedicine should be able to help heal the hearts of people that have already been victims of heart disease and  heart attacks .  On the other hand, it will also play a key role in finding people with a high risk of having heart disease, and will be able to help prevent heart attacks from happening in the first place.  Nanotechnology of the heart is a lot less invasive than surgery because everything is occurring at a minuscule level in the body compared to relatively large tissues that are dealt with in surgery.  With our technology today,  heart surgeries  are performed to treat the damaged heart tissue that resulted from a heart attack.  This is a major surgery that usually takes a couple of months to recover from ("WebMD - Better Information. Better Health").  During this period, patients are extremely limited in the activities that they can do.  This long recovery process is an inconvenience to the patients, and with the growth of medicine it most likely won't be very long before a more efficient method for treating heart attack patients will be developed and used. [ citation needed ]  The method that is the frontrunner to replace major heart surgery is the use of nanotechnology.  There are a couple alternate ways to heart surgery that nanotechnology will potentially be able to offer in the future.


With people that have heart disease or that have suffered a heart attack, their hearts are often damaged and weakened.  The more minor forms of  heart failure  do not require surgery and are often treated with  medications  ("WebMD - Better Information. Better Health").  The use of nanotechnology on treating damaged hearts will not replace these milder heart problems, but rather the more serious heart problems that currently require surgery or sometimes even  heart transplants .


A group of engineers, doctors and materials scientists at  MIT  and  Children's Hospital Boston  have teamed together and are starting the movement of finding a way to use nanotechnology to strengthen the weakened heart tissue ("MIT - Massachusetts Institute of Technology"). The first method uses nanotechnology combined with  tissue engineering , and gold  nanowires  are placed and woven into the damaged parts of the heart, essentially replacing the non-functioning or dead tissues. [ 2 ]


The other approach would potentially use minuscule  nanoparticles  that would travel through the body and find dying heart tissue.  The nanoparticles would be carrying objects such as " stem cells ,  growth factors , drugs and other therapeutic compounds,". [ 2 ]   Then the nanoparticles would release the compounds and inject them into the damaged heart tissue.  This would theoretically lead to the regeneration of the tissue. [ 2 ]


Being able to fix cardiac tissue that has been damaged from a heart attack or heart disease is not very simple and it is one of the major challenges today in the field of tissue engineering (" Popular Science "). This is because heart cells are not the easiest objects to create in a lab.  It takes an enormous amount of special care and work to develop the cells so that they beat in sync with one another ("Popular Science"). Even after the heart cells have finally been made, it is also a large task to insert the cells into the inoperable parts of the heart and to get them working in unison with the tissues that were still working properly ("Popular Science").


There have been several successful examples of this with the use of a "stem-cell- based heart patch developed by  Duke University  researchers," ("Popular Science").  The  biomaterials  that make up the patch are usually made of either biological polymers like  alginate  or synthetic polymers such as  polylactic acid  ("Nature Nanotechnology").  These materials are good at organizing the cells into functioning tissues; however they act as insulators and are poor conductors of electricity, which is a major problem especially in the heart ("Nature Nanotechnology"). Since the electrical signals that are sent between calcium ions are what control when the  cardiomyocytes  of the heart contract, which makes the heart beat, the stem-cell heart patch is not very efficient and not as effective as doctors would like it to be ("Popular Science"). The results of the patch not being very conductive is that the cells are not able to attain a smooth, continuous beat throughout the entire tissue containing the stem cells.  This results in the heart not functioning properly, which in turn could mean that more heart problems might arise due to the implanting of the stem cells.


Recently [ when? ]  there have been some new developments in the field of nanotechnology that will be more efficient than the poorly conducting stem-cell-based patch ("Nature Nanotechnology"). Scientists and researchers found a way for these stem cell patches (also known as tissue scaffolds) to be conductive and therefore become exponentially [ citation needed ]  more effective ("Nature Nanotechnology").  They found that by growing gold nanowires into and through the patches, they were able to greatly increase the  electrical conductivity . [ 2 ]   The nanowires are thicker than the original scaffold and the cells are better organized as well. [ 2 ]  There is also an increase in production of the proteins needed for muscle calcium binding and contraction. [ 2 ]  The gold nanowires poke through the stem cell's scaffolding material, which strengthens the electrical communication between surrounding heart cells. [ 2 ]   Without the nanowires, the stem cell patches produced a minute current and the cells would only beat in small clusters at the stimulation origin. [ 2 ]  With the nanowires, the cells seem to contract together even when they are clustered far away from the source of stimulation. [ 2 ]  The use of gold nanowires with the stem cell heart patches is still a relatively new concept and it will probably be awhile before they will be used in humans. It is hoped that the nanowires will be tested in live animals in the near future. [ 2 ]


Another way that nanotechnology will potentially be used to help fix damaged heart tissues is through the use of guided nanoparticle "missiles". [ 2 ]   These nanoparticles can cling to and attach to artery walls and secrete medicine at a slow rate ("MIT-Massachusetts Institute of Technology"). The particles, known as nanoburrs due to the fact that they are coated with little protein fragments that stick to and target certain proteins.  The nanoburrs can be made to release the drug that is attached to them over the course of several days ("MIT-Massachusetts Institute of Technology").  They are unique compared to regular drugs because they can find the particular damaged tissue, attach to it, and release the drug payload that is attached to it ("MIT-Massachusetts Institute of Technology"). What happens is the nanoburrs are targeted to a certain structure, known as the  basement membrane ; this membrane lines the arterial walls and is only present if the area is damaged. Nanoburrs could be able to carry drugs that are effective in treating the heart, and also potentially carry stem cells to help regenerate the damaged heart tissue ("MIT-Massachusetts Institute of Technology").


The particles are made up of three different layers and are sixty nanometers in diameter ("MIT-Massachusetts Institute of Technology").The outer layer is a coating of  polymer  called PEG, and its job is to protect the drug from disintegrating while it is traveling through the body.  The middle layer consists of a fatty substance and the inner core contains the actual drug along with a polymer chain, which controls the amount of time it will take before the drug is released ("MIT-Massachusetts Institute of Technology").


In a study done on rats, the nanoparticles were injected directly into the rat's tail and they still were able to reach the desired target (the left  carotid artery ) at a rate that was twice the amount of the non-targeted nanoparticles ("MIT-Massachusetts Institute of Technology"). Because the particles can deliver drugs over a long period of time, and can be injected intravenously, the patients would not need to have multiple repeated injections, or invasive surgeries on the heart which would be a lot more convenient. The only downside to this is that the existing delivery approaches are invasive, requiring either a direct injection into the heart,  catheter  procedures, or surgical implants. [ 2 ]   There is no question, however, that the future of heart repairs and heart disease/attack prevention will definitely involve the use of nanotechnology in some way. [ citation needed ]


Polyketal nanoparticles are pH-sensitive, hydrophobic nanoparticles formulated from poly(1-4-phenyleneacetone dimethylene ketal). [ 3 ]  They are an acid-sensitive vehicle of drug delivery, specifically designed for targeting the environments of tumors, phagosomes, and inflammatory tissue. [ 3 ]  In such acidic environments, these nanoparticles undergo accelerated hydrolysis into low molecular weight hydrophilic compounds, consequently releasing their therapeutic contents at a faster rate. [ 3 ]  Unlike polyester-based nanoparticles, polyketal nanoparticles do not generate acidic degradation products following hydrolysis  [ 3 ] [ 4 ]


Post- myocardial infarction , inflammatory  leukocytes  invade the  myocardium . Leukocytes contain high amounts of  Nicotinamide adenine dinucleotide phosphate  (NADPH) and Nox2. [ 5 ] [ 6 ]  Nox2 and NADPH oxidase combine to act as a major source of cardiac  superoxide  production, which in excess can lead to  myocyte  hypertrophy, apoptosis, fibrosis, and increased matrix  metalloproteinase -2 expression. [ 5 ]  In a mouse-model study by Somasuntharam et al. 2013, polyketal nanoparticles were used as a delivery vehicle for  siRNA  to target and inhibit Nox2 in the infarcted heart. [ 7 ]  Following intramyocardial injection in vivo, Nox2-siRNA nanoparticles prevented  upregulation  of Nox2-NADPH  oxidase , and improved  fractional shortening . [ 7 ]  When taken up by macrophages in the myocardium following a MI, the nanoparticles degraded in the acidic environment of the  endosomes / phagosomes , releasing Nox2-specific siRNA into the  cytoplasm . [ 7 ]


Polyketal nanoparticles have also been used in the infarcted mouse heart to prevent  ischemia - reperfusion injury  caused by  reactive oxygen species  (ROS). [ 8 ]  Levels of the  antioxidant  Cu/Zn-superoxide dismutase (SOD1), which scavenges harmful ROS, decrease following MI. [ 9 ]  SOD1-enacapsulated polyketal nanoparticles are able to scavenge reperfusion-injury induced ROS. [ 8 ]  Furthermore, this treatment improved fractional shortening, suggesting the benefit of targeted delivery by polyketals. One of the key advantages of polyketal use is that they do not exacerbate the inflammatory response, even when administered at concentrations exceeding therapeutic limits. [ 10 ]  In contrast to commonly used  poly(lactic-co-glycolic acid)  (PLGA) nanoparticles, polyketal nanoparticle administration in mice instigates little recruitment of inflammatory cells. [ 10 ]  Additionally, intramuscular injection of polyketals into the leg of rats shows no significant increases in inflammatory  cytokines  such as  IL-6 ,  IL-1ß ,  TNF-α  and  IL-12 . [ 10 ]


The  Most Sacred Heart of Jesus  ( Latin :  Cor Jesu Sacratissimum ) is one of the most widely practised and well-known  Catholic devotions , wherein the heart of  Jesus Christ  is viewed as a symbol of "God's boundless and passionate love for mankind". [ 1 ]  This devotion to Christ is predominantly used in the  Catholic Church , followed by  high church   Anglicans , and some  Western Rite Orthodox . In the  Latin Church , the liturgical  Solemnity of the Most Sacred Heart of Jesus  is celebrated on the third Friday after  Pentecost . [ 2 ]  The 12 promises of the Most Sacred Heart of Jesus are also popular.


The devotion is especially concerned with what the church deems to be the long-suffering love and compassion of the heart of Christ towards humanity. The popularization of this devotion in its modern form is derived from a Roman Catholic  nun  from  France ,  Margaret Mary Alacoque , who said she learned the devotion from Jesus during a series of  apparitions  to her between 1673 and 1675, [ 3 ]  and later, in the 19th century, from the mystical revelations of another Catholic nun in  Portugal ,  Mary of the Divine Heart , a  religious sister  of the  congregation of the Good Shepherd , who requested in the name of Christ that  Pope Leo XIII  consecrate the entire world to the Sacred Heart of Jesus. Predecessors to the modern devotion arose unmistakably in the  Middle Ages  in various facets of  Catholic mysticism , particularly with  Gertrude the Great . [ 4 ]


The Sacred Heart is often depicted in  Christian art  as a flaming heart [ 5 ]  shining with divine light, pierced by the lance-wound, encircled by the  crown of thorns , surmounted by a cross, and bleeding. Sometimes, the image is shown shining within the bosom of Christ with his wounded hands pointing at the heart. The wounds and crown of thorns allude to the manner of  Christ's passion , while the flames represent a furnace of ardent love. [ 6 ]


Historically, the devotion to the Sacred Heart is an outgrowth of devotion to what is believed to be Christ's sacred humanity. [ 7 ]  During the first ten centuries of Christianity, there is nothing to indicate that any worship was rendered to the wounded Heart of Jesus. [ 8 ]  The revival of religious life and the zealous activity of  Bernard of Clairvaux  and  Francis of Assisi  in the twelfth and thirteenth centuries, together with the enthusiasm of the Crusaders returning from the Holy Land, gave a rise to devotion to the Passion of Jesus Christ and particularly to practices in honour of the  Sacred Wounds . [ 9 ]


Devotion to the Sacred Heart developed out of the devotion to the Holy Wounds, in particular to the Sacred Wound in the side of Jesus. The first indications of devotion to the Sacred Heart are found in the eleventh and twelfth centuries in the fervent atmosphere of the  Benedictine  or  Cistercian   monasteries . [ 10 ]  It is impossible to say with certainty what were its first texts or who were its first devotees.


Bernard of Clairvaux ( d.  1153) said that the piercing of Christ's side revealed his goodness and the charity of his heart for humanity. The earliest known hymn to the Sacred Heart,  "Summi Regis Cor Aveto" , is believed to have been written by the Norbertine Herman Joseph (d. 1241) of Cologne, Germany. The hymn begins: "I hail Thee kingly Heart most high."


From the 13th to the 16th centuries, the devotion was propagated but it did not seem to have been embellished. It was everywhere practised by individuals and by different religious congregations, such as the  Franciscans ,  Dominicans , and  Carthusians . Among the Franciscans the devotion to the Sacred Heart of Jesus has its champions in  Bonaventure  (d. 1274) in his  Vitis Mystica  ("Mystic Vine") and John de la Verna. [ 11 ]  Bonaventure wrote: "Who is there who would not love this wounded heart? Who would not love in return Him, who loves so much?" [ 12 ]  It was, nevertheless, a private, individual devotion of the mystical order. Nothing of a general movement had been inaugurated, except for similarities found in the devotion to the  Five Holy Wounds  by the Franciscans, in which the wound in Jesus's heart figured most prominently.


Bonaventure's  Opusculum 3, Lignum vitae  (a part from which is the reading for the  Divine Office  on the Solemnity of the Sacred Heart) refers to the heart as the fountain from which God's love poured into one's life:


Take thought now, redeemed man, and consider how great and worthy is he who hangs on the cross for you. His death brings the dead to life, but at his passing heaven and earth are plunged into mourning and hard rocks are split asunder. It was a divine decree that permitted one of the soldiers to open his sacred side with a lance. This was done so that the Church might be formed from the side of Christ as he slept the sleep of death on the cross, and so that the Scripture might be fulfilled: 'They shall look on him whom they pierced'. The blood and water, which poured out at that moment, were the price of our salvation. Flowing from the secret abyss of our Lord's heart as from a fountain, this stream gave the sacraments of the Church the power to confer the life of grace, while for those already living in Christ it became a spring of living water welling up to life everlasting. [ 13 ]


According to  Thomas Merton ,  Lutgarde  (d. 1246), a Cistercian mystic of  Aywieres , Belgium, was one of the great precursors of the devotion to the Sacred Heart of Jesus. A contemporary of Francis of Assisi, she "entered upon the mystical life with a vision of the pierced Heart of the Saviour, and had concluded her mystical espousals with the Incarnate Word by an exchange of hearts with Him." [ 14 ]  Sources say that Christ came in a visitation to Lutgarde, offering her whatever gift of grace she should desire; she asked for a better grasp of Latin, that she might better understand the word of God and sing God's praise. Christ granted her request and Lutgarde's mind was flooded with the riches of psalms, antiphons, readings, and responsories. However, a painful emptiness persisted. She returned to Christ, asking to return his gift, and wondering if she might, just possibly, exchange it for another. "And for what would you exchange it?" Christ asked. "Lord, I would exchange it for your Heart." Christ then reached into Lutgarde and, removing her heart, replaced it with his own, at the same time hiding her heart within his breast. [ 15 ]


Mechtilde of Helfta  (d. 1298) became an ardent devotee and promoter of Jesus' heart after it was the subject of many of her visions. The idea of hearing the heartbeat of God was very important to medieval saints who nurtured devotion to the Sacred Heart. [ 16 ]  Mechtilde reported that Jesus appeared to her in a vision and commanded her to love him ardently, and to honor his sacred heart in the  Blessed Sacrament  as much as possible. He gave her his heart as a pledge of his love, as a place of refuge during her life and as her consolation at the hour of her death. From this time Mechtilde had an extraordinary devotion for the Sacred Heart, and said that if she had to write down all the favors and all the blessings which she had received by means of this devotion, a large book would not contain them. [ 17 ]


Gertrude the Great  was an early devotee of the Sacred Heart of Jesus. [ 18 ]  Book 2 of the  Herald of Divine Love  ( Latin :  Legatus divinæ pietatis ) vividly describes Gertrude's visions, which show a considerable elaboration on the hitherto ill-defined veneration of Christ's heart. Bernard articulated this in his commentary on the  Song of Songs . The women of  Helfta  – Gertrude foremost, who surely knew Bernard's commentary, and to a somewhat lesser extent the two Mechthildes – experienced this devotion centrally in their mystical visions. [ 19 ]


In the 16th century, the devotion passed from the domain of  mysticism  into that of  Christian asceticism . It was established as a devotion with prayers already formulated and special exercises, found in the writings of Lanspergius (d. 1539) of the  Carthusians  of Cologne, the Benedictine  Louis de Blois  (d. 1566)  Abbot  of  Liessies  in  Hainaut ,  John of Avila  (d. 1569), and  Francis de Sales  (d. 1622).


The historical record from that time shows an early bringing to light of the devotion. Ascetic writers spoke of it, especially those of the  Society of Jesus  (Jesuits). The image of the Sacred Heart of Jesus was everywhere in evidence, largely due to the Franciscan devotion to the  Five Wounds  and to the Jesuits placing the image on the title-page of their books and on the walls of their churches.


The first to establish the theological basis for the devotion was Polish Jesuit  Kasper Drużbicki  (1590–1662) in his book  Meta cordium – Cor Jesu  ( The goal of hearts – Heart of Jesus ). Not much later  John Eudes  wrote an office, and promoted a feast for it. John Eudes is regarded as "tireless apostle of the devotion of the Sacred Hearts", [ 20 ]  entitling him as 'Father', doctor and apostle of the liturgical cult of the hearts of Jesus and Mary. [ 21 ]


Little by little, the devotion to the Sacred Hearts became distinct, and on 31 August 1670 the first feast of the Sacred Heart of Jesus was celebrated in the Grand Seminary of  Rennes .  Coutances  followed suit on October 20, a day with which the  Eudist  feast was from then on to be connected. The feast soon spread to other dioceses, and the devotion was likewise adopted in various religious communities. It gradually came into contact with the devotion begun by  Margaret Mary Alacoque  at  Paray-le-Monial , and the two merged.


The most significant source for the devotion to the Sacred Heart in the form it is known today was Margaret Mary Alacoque (1647–1690), a nun of the  Order of the Visitation of Holy Mary , who claimed to have received Sacred Heart revelations from  Jesus Christ  between 1673 and 1675 in the Burgundian French village of  Paray-le-Monial .


The first apparition took place on 27 December 1673, the day of the feast of Saint  John the Evangelist , during which Jesus allowed Margaret Mary to rest her head upon his heart, telling her that he wanted to make his love known to all mankind and that he had chosen her to spread the devotion to his Sacred Heart. Right after this, she had a vision of his heart with a crown of thorns, surrounded by flames and above which a cross was planted. [ 22 ]  This representation will become the popular image of the Sacred Heart which Margaret Mary used to propagate the devotion.


Between 1674 and 1675, other apparitions followed in which  Jesus Christ  revealed to Alacoque different forms of devotion to the Sacred Heart. The  First Fridays Devotion , which is the reception of  Holy Communion  on nine first Fridays of each month, was revealed to her through a "Great Promise" of final penance granted to those who practice this act of  reparation . [ 23 ]  Margaret Mary also said that she was instructed to spend an hour every Thursday night, from eleven to midnight, to pray and meditate on Jesus' agony in the Garden of Gethsemane. Her prayers intended to ask mercy for sinners as well as to make reparation for the abandonment Jesus felt from his apostles in the garden. This practice is now known as the " Holy Hour " [ 24 ]  and is also frequently performed during an hour of  Eucharistic adoration .


During the  octave  of  Corpus Christi  in 1675, probably on June 16, the vision known as the "great revelation" reportedly took place, where Jesus said: "Behold the heart which has so loved men that it has spared nothing, even to exhausting and consuming itself, in order to testify its love; and in return, I receive from the greater part only ingratitude, by their irreverence and sacrilege, and by the coldness and contempt they have for me in this sacrament of love." [ 25 ]  He then asked Margaret Mary for a feast of reparation of the Friday after the octave of Corpus Christi, bidding her consult her confessor  Claude de la Colombière , then superior of the small Jesuit house at Paray-le-Monial. [ 26 ]  This request was transmitted and the  feast of the Sacred Heart  was progressively instituted throughout the Church. The feast later became a  solemnity  in the  liturgical calendar , a feast of the highest rank, celebrated eight days after the Feast of Corpus Christi just as Jesus requested. On 21 June 1675, following that apparition, Claude consecrated himself to the Sacred Heart, making him the first person to be  consecrated to the Sacred Heart of Jesus  after Margaret Mary, and began spreading the devotion. [ 27 ] [ 28 ]


De la Colombière directed her to write an account of the apparitions, which he discreetly circulated in France and England. After his death on 15 February 1682, his journal of spiritual retreats was found to contain a copy in his handwriting of the account that he had requested of Margaret Mary, together with a few reflections on the usefulness of the devotion. This journal, including the account – an "offering" to the Sacred Heart in which the devotion was explained – was published at Lyon in 1684. The little book was widely read, especially at Paray-le-Monial. Margaret Mary reported feeling "dreadful confusion" over the book's contents, but resolved to make the best of it, approving of the book for the spreading of her cherished devotion. Along with the Visitandines, priests,  religious , and laymen espoused the devotion, particularly the  Capuchins . The reported apparitions served as a catalyst for the promotion of the devotion to the Sacred Heart. [ 29 ]  In 1691 Jesuit priest John Croiset wrote a book called  De la Dévotion au Sacré Cœur , and  Joseph de Gallifet  promoted the devotion. The mission of propagating the new devotion was especially confided to the religious of the Visitation and to the priests of the Society of Jesus.


Alacoque said that in her apparitions Jesus promised specific blessings to those who practice devotion to his Sacred Heart. The last promise, also called the "Great Promise", is a promise of final penance granted to those who practice the First Fridays Devotion.


Another source for the devotion to the Sacred Heart of Jesus was  Mary of the Divine Heart  (1863–1899), a  religious sister  from the  Congregation of Our Lady of Charity of the Good Shepherd , who reported to have received several  interior locutions  and visions of Jesus Christ. The first interior locution Mary of the Divine Heart reported was during her youth spent with the family in the  Castle of Darfeld  [ de ] , near  Münster , Germany, and the last vision and private revelation was reported during her presence as mother superior in the Convent of the Sisters of the Good Shepherd in  Porto , Portugal.


Based on the messages she said she received in her revelations of Christ, on 10 June 1898 her confessor at the Good Shepherd monastery wrote to  Pope Leo XIII  stating that Mary of the Divine Heart had received a message from Christ, requesting the pope to consecrate the entire world to the Sacred Heart. The pope initially attached no credence to it and took no action. However, on 6 January 1899 she sent another letter asking that in addition to the consecration, the first Fridays of the month be observed in honor of the Sacred Heart.


Mary of the Divine Heart died in her monastery in  Portugal  when the church was singing the first vespers of the Sacred Heart of Jesus on 8 June 1899. The following day, in  Annum sacrum ,  Pope Leo XIII  consecrated the entire world to the Sacred Heart of Jesus.


Mary of the Divine Heart said that in her mystical experiences Jesus Christ inspired her to build a shrine dedicated to his Sacred Heart. According to the writings of Sister Mary of the Divine Heart, Jesus said: "I will make it a place of graces. I will distribute copiously graces to all who live in this house [the convent], those who live here now, those who will live here after, and even to their relatives." [ 30 ]


She did not live to see this come to fruition. The imposing  Church of the Sacred Heart of Jesus  (also referred as Church of the Good Shepherd or Sanctuary of the Sacred Heart of Jesus) was built between 14 July 1957 and 21 April 1966, in the civil parish of  Ermesinde  in north  Portugal , and consecrated to the Heart of Christ in fulfillment of the vow made by the nun. She is buried in the Church of the Sacred Heart of Jesus in  Ermesinde .


In 1353,  Pope Innocent VI  instituted a Mass honoring the mystery of the Sacred Heart. [ 29 ]


In 1693 the  Holy See  imparted  indulgences  to the Confraternities of the Sacred Heart, and in 1697 granted the feast to the Visitandines with the Mass of the Five Wounds, but refused a feast common to all, with special Mass and Office. The devotion spread, particularly in religious communities. The  Marseille plague  in 1720 furnished perhaps the first occasion for a solemn consecration and public worship outside of religious communities. Other cities of southern Europe followed the example of Marseille.


After Pope Leo XIII received correspondence from Mary of the Divine Heart asking him to consecrate the entire world to the Sacred Heart of Jesus, he commissioned a group of theologians to examine the petition on the basis of revelation and sacred tradition. The outcome of this investigation was positive, and in 1899 he decreed that the consecration of the entire human race to the Sacred Heart of Jesus should take place on 11 June 1899. The  encyclical letter  also encouraged the entire Roman Catholic episcopate to promote the  First Friday Devotions , established June as the Month of the Sacred Heart, and included the  Prayer of Consecration to the Sacred Heart . [ 31 ]  The idea of this act, which Leo XIII called "the great act" of his pontificate.


Pope Pius X  decreed that the consecration of the human race performed by Leo XIII be renewed each year. Pius X also granted a Pontifical decree for the imposition of a golden crown to the lowly foot of a statue of the Sacred Heart of Jesus in the  Nevers Cathedral  on 9 July 1908 (via the Archbishop of  Nevers  and  Besancon , Francois Leon Gauthey, both signed and notarized by the  Sacred Congregation of Rites ).


Pope Pius XI  affirmed the church's position with respect to Margaret Mary Alacoque's visions of Jesus Christ by stating that Jesus had "manifested Himself" to Alacoque and had "promised her that all those who rendered this honor to his Heart would be endowed with an abundance of heavenly graces". [ 32 ]  His encyclical letter  Miserentissimus Redemptor  (1928) reaffirmed the importance of consecration and reparation to the Sacred Heart of Jesus.


By inserting the "Great Promise" of the First Fridays Devotion into the  Bull of Canonization  of  Margaret Mary Alacoque  on 13 May 1920,  Pope Benedict XV  encouraged the practice of this  act of reparation  of the  first nine fridays  in honor of the Sacred Heart. [ 33 ]