Due to the reentrant nature of atrial flutter, it is often possible to ablate the circuit that causes atrial flutter with  radiofrequency catheter ablation  or  pulsed field ablation . Catheter ablation wasconsidered to be a first-line treatment method for many people with typical atrial flutter due to its high rate of success (>90%) and low incidence of complications, [ 1 ]  although pulsed field ablation now offers a non-thermal option. This is done in the cardiac electrophysiology lab by causing a ridge of scar tissue in the cavotricuspid isthmus that crosses the path of the circuit that causes atrial flutter. Eliminating conduction through the isthmus prevents reentry, and if successful, prevents the recurrence of the atrial flutter. Atrial fibrillation often occurs (30% within 5 years) after catheter ablation for atrial flutter. [ 1 ]


Auenbrugger's sign  is a bulging of the  epigastrium  seen in cases of severe  pericardial effusion . It is often not spotted because pericardial effusion can be caught on  echocardiography  before it progresses this far. [ 1 ]  It is named after  Joseph Leopold Auenbrugger . [ citation needed ]


Auenbrugger's sign  at  Who Named It?


This  medical sign  article is a  stub . You can help Wikipedia by  expanding it .


The  Baskerville effect , or the  Hound of the Baskervilles effect , is the alleged  self-fulfilling prophecy  that there is an increase in rate of mortality through  heart attacks  on days considered unlucky because of the psychological stress this causes on superstitious people.  The term derives from the  Sherlock Holmes   novel   The Hound of the Baskervilles  in which a hellish-looking dog chases Sir Charles Baskerville, sufferer of a chronic heart disease. According to legend, the dog cursed his family, Baskerville runs in great fear and dies of a heart attack "with an expression of horror in his face".


The Baskerville effect was named by David Phillips and his colleagues at the  University of California, San Diego , on a paper where they reported that the daily number of deaths of  Chinese  and  Japanese Americans  from heart attacks between 1973 and 1998 was 7 percent higher on the fourth of the month compared to the average for the other days in that month, while this was not observed in the general American population. [ 1 ]


Four (四, formal writing: 肆,  pinyin  si4) is considered an  unlucky number  in  Chinese , and hence in the  Japanese  and  Korean , because it sounds like "death" (死  pinyin  si3).  Some Chinese and Japanese  hotels  and hospitals do not use it as a room number (the way that American architects don't use 13 as a floor number in office or hotel buildings). The authors, seeing how telephone line subscribers could choose the last four digits in their telephone numbers, found evidence that  the number 4 is avoided  among Chinese and Japanese Americans by searching the California Yellow Pages for telephone numbers of Chinese and Japanese restaurants, and finding that these had significantly fewer numbers 4 in this last section (366 out of 4748, or 7.71 percent) than it would be expected by chance (10 percent), a pattern not observed on restaurants listed as American. [ 1 ]  An analysis of the 20,000 computerized death certificates of Asian-Americans in San Diego, Phillips discovered that there was a 13 percent uptick in death rates on the fourth of the month. [ 2 ] [ 3 ]  The hypothesis was that the peak was caused by stress induced by the  superstition  surrounding this number. [ 1 ]


In 2002,  Gary Smith  commented that Phillips and colleagues had omitted data from several heart disease categories, picking only those that happened to have a higher rate on the fourth day, calling them "chronic heart diseases".  Smith also pointed out that they had not done this on their previous studies of Jewish deaths near  Passover  and Chinese deaths near the  Harvest Moon , where they had used all heart disease categories. [ 4 ]


Smith also found no statistically relevant peaks on day 4 in data from 1969–1988 and 1999–2001 for total coronary deaths, inpatients, or the subset of heart diseases used by Phillips and colleagues, adding that there were more deaths on day 5 in the 1969–1988 data, and more deaths on day 3 in the 1999–2001 data. [ 4 ]


In 2003, Nirmal Panesar and colleagues looked for this effect on the Chinese population of  Hong Kong .  They looked at mortality data from 1995 to 2000, comparing the days of the month with "deathly connotations" (4, 14 and 24) with the other days of the month on both the  Lunar  and  Gregorian  calendars, and found no statistically significant difference. [ 5 ]


In early 2018,  Jonathan Jarry  analysed this phenomenon, citing both Smith's and Panesar et al's papers, pointing out that, if the effect was real, a bigger effect would be seen in Asia, while the opposite occurs. [ 6 ]  Jarry states that the peak observed on the original study appears because of what the researchers decided to compare it to, and quotes cardiologist  Christopher Labos  as concluding that "while the number of deaths on day 4 may be higher than average, it is not actually statistically higher than any individual day."


Bendopnea  is a newly described symptom, normally of  heart failure , meaning  shortness of breath  felt when leaning forward. [ 1 ] [ 2 ] [ 3 ] [ 4 ] [ 5 ]  It was introduced by Thibodeau et al. in 2014. [ 1 ] [ 2 ]  Patients with heart failure often experience this when bending over to tie a shoe, putting socks on, or other activities requiring bending downwards. [ 1 ] [ 2 ]  It has been defined as occurring within 30 seconds of bending over, but could occur in as few as 8 seconds in severe cases. [ 3 ]  When a patient is in heart failure, it often means the  ventricular filling pressures  are high at baseline. [ 1 ] [ 2 ]  When said person bends forward, it causes a further increase in ventricular filling pressures that causes dyspnea, especially in patients with lower  cardiac indices . [ 1 ] [ 2 ]


The term "bendopnea" (meaning "bent" and "breath") was coined to be easily identifiable among patients and physicians. [ 3 ]


Bendopnea should be distinguished from  orthopnea  (shortness of breath while lying down),  trepopnea  (shortness of breath while lying on one side), and  platypnea  (shortness of breath relieved by lying down and worsened when upright) with or without  orthodeoxia  (oxygen desaturation).


This medical  symptom  article is a  stub . You can help Wikipedia by  expanding it .


A  bioartificial heart  is an engineered  heart  that contains the  extracellular structure  of a  decellularized  heart and cellular components from a different source. Such hearts are of particular interest for therapy as well as research into  heart disease . The first bioartificial hearts were created in 2008 using cadaveric rat hearts. [ 1 ] [ 2 ] [ 3 ]  In 2014, human-sized bioartificial pig hearts were constructed. [ 4 ]  Bioartificial hearts have not been developed yet for clinical use, although the recellularization of porcine hearts with human cells opens the door to  xenotransplantation . [ 4 ] [ 5 ]


Heart failure is one of the leading causes of death. In 2013, an estimate of 17.3 million deaths per year out of the 54 million total deaths was caused by cardiovascular diseases, meaning that 31.5% of the world's total death was caused by this. [ 6 ]  Often, the only viable treatment for end-stage heart failure is organ transplantation. [ 5 ]  Currently organ supply is insufficient to meet the demand, which presents a large limitation in an end-stage treatment plan. [ 2 ] [ 5 ]  A theoretical alternative to traditional transplantation processes is the engineering of personalized bioartificial hearts. Researchers have had many successful advances in the engineering of cardiovascular tissue and have looked towards using decellularized and recellularized cadaveric hearts in order to create a functional organ. [ 5 ]  Decellularization-recellularization involves using a cadaveric heart, removing the cellular contents while maintaining the protein matrix ( decellularization ), and subsequently facilitating growth of appropriate cardiovascular tissue inside the remaining matrix (recellularization). [ 5 ]


Over the past years, researchers have identified populations of cardiac stem cells that reside in the adult human heart. This discovery sparked the idea of regenerating the heart cells by taking the stem cells inside the heart and reprogramming them into cardiac tissues. [ 7 ]  The importance of these stem cells are self-renewal, the ability to differentiate into  cardiomyocytes , endothelial cells and smooth vascular muscle cells, and clonogenicity. These stem cells are capable of becoming  myocytes , which are for stabilizing the topography of the intercellular components, as well as to help control the size and shape of the heart, as well as vascular cells, which serve as a cell reservoir for the turnover and the maintenance of the mesenchymal tissues. [ 7 ]  However,  in vivo  studies have demonstrated that the regenerative ability of implanted cardiac stem cells lies in the associated macrophage-mediated immune response and concomitant fibroblast-mediated wound healing and not in their functionality, since these effects were observed for both live and dead stem cells. [ 8 ]


The preferred method to remove all cellular components from a heart is perfusion decellularization. This technique involves perfusing the heart with detergents such as  SDS  and  Triton X-100  dissolved in  distilled water . [ 1 ]


The remaining ECM is composed of structural elements such as collagen, laminin, elastin and fibronectin. The ECM scaffold promotes proper cellular proliferation and differentiation, vascular development, as well as providing mechanical support for cellular growth. [ 5 ]  Because minimal DNA material remains after the decellularization process, the engineered organ is biocompatible with the transplant recipient, regardless of species.  Unlike traditional transplant options, recellularized hearts are less immunogenic and have a decreased risk of rejection. [ 2 ] [ 9 ]


Once the decellularized heart has been sterilized to remove any pathogens, the recellularization process can occur. [ 2 ]  Multipotent cardiovascular progenitors are then added to the decellularized heart and with additional exogenous growth factors, are stimulated to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells. [ 10 ]


The most promising results come from recellularized rat hearts. After only 8 days of maturation, the heart models were stimulated with an electrical signal to provide pacing. The heart models showed a unified contraction with a force equivalent to ~2% of a normal rat heart or ~25% of that of a 16-week-old human heart. [ 1 ] [ 5 ]


Although far from use in a clinical setting, there have been great advances in the field of bioartificial heart generation. [ 2 ] [ 5 ] [ 10 ]   The use of decellularization and recellularization processes, has led to the production of a three dimensional matrix that promotes cellular growth; the repopulation of the matrix containing appropriate cell composition; and the bioengineering of organs demonstrating functionality (limited) and responsiveness to stimuli. [ 2 ] [ 5 ]  This area shows immense promise and with future research may redefine treatment of end stage heart failure.


The  Biomedical Research Center  (BRC) is a research center at  Qatar University  focusing on biomedical research. BRC was founded in 2014, and partners with the  Ministry of Public Health (Qatar) , and  Hamad Medical Corporation (HMC) . [ 1 ] [ 2 ] [ 3 ]


The incidence of genetic disorders in  Qatar  is high, [ 4 ]  with the top three causes of death in the country being cancer, heart diseases, and diabetes. [ 5 ] [ 6 ]  The government saw the creation of BRC as a strategy for proactively preventing diseases to help foster public health. [ 7 ] [ 8 ]


BRC labs received the  ISO/IEC - 17025  accreditation from the American Association for Laboratory Accreditation (A2LA). [ 9 ]  This research center focus on  infectious diseases  ( virology  and  microbiology ),  metabolic disorders , and biomedical  omics . [ 10 ]


Since its establishment in 2014, the BRC has published over 530 research papers. [ 11 ] [ 12 ]  The centre's research projects encompass a range of areas, including:


BRC Introduced the use of  zebrafish  as an animal model in biomedical research [ 36 ] [ 37 ] [ 32 ] [ 38 ] [ 39 ] [ 40 ]  and established a facility for it in 2015. [ 41 ] [ 42 ] [ 43 ]  The facility is used as a research unit to study many genetic diseases. [ 32 ]  The Ministry of Public Health articulated an institutional research policy (IRP) on the use of zebrafish in research, [ 44 ]  which Qatar University backed.


The BRC facilities include: [ 41 ]


A  bioresorbable stent  is a tube-like device ( stent ) that is used to open and widen clogged heart arteries and then dissolves or is absorbed by the body. It is made from a material that can release a drug to prevent scar tissue growth. It can also restore normal vessel function and avoid long-term complications of metal stents. [ 1 ] [ 2 ]


In medicine, a  stent  is any device which is inserted into a  blood vessel  or other anatomical internal duct to expand it to prevent or alleviate a blockage.  Traditionally, such devices are fabricated from metal mesh and remain in the body permanently or until removed through further surgical intervention.  A bioresorbable stent (also called bioresorbable scaffold, biodegradable stent or naturally-dissolving stent) serves the same purpose, but is manufactured from a material that may dissolve or be absorbed in the body. [ 3 ]


The use of metal  drug-eluting stents  presents some potential drawbacks. These include a predisposition to late stent  thrombosis , prevention of late vessel adaptive or expansive remodeling, hindrance of surgical revascularization, and impairment of imaging with multislice  CT . [ 4 ] [ 5 ]


To overcome some of these potential drawbacks, several companies are pursuing the development of bioresorbable scaffolds or bioabsorbable stents. Like metal stents, placement of a bioresorbable stent will restore blood flow and support the vessel through the healing process. However, in the case of a bioresorbable stent, the stent will gradually resorb and be benignly cleared from the body, enabling a natural reconstruction of the arterial wall and restoration of vascular function. [ 6 ]


Studies have shown that the most critical period of vessel healing is largely complete by approximately three to nine months. [ 6 ] [ 7 ] [ 8 ]   Therefore, the goal of a bioresorbable or "temporary" stent is to fully support the vessel during this critical period, and then resorb from the body when it is no longer needed.


Bioabsorbable scaffolds, or naturally dissolving stents, that have been investigated include base materials that are either metals or polymers. While polymer-based scaffolds had a strong presence at first, they have meanwhile lost some appeal due to safety concerns and focus is now moved towards metallic magnesium-based scaffolds. [ 9 ]


Metal stent candidates are  magnesium ,  iron ,  zinc  and their alloys. [ 10 ]


Magnesium -based scaffolds have been approved for use in several countries around the world. The only commercially available magnesium-based scaffold consists of a magnesium alloy, approximately 95% of which resorbs within one year of implantation. [ 11 ] [ 12 ] [ 13 ]  Thousands of commercially available magnesium-based scaffolds have been implanted. Clinical results suggest that magnesium-based scaffolds may be a viable option in avoiding the drawbacks of permanent stents. [ 14 ] [ 15 ] [ 16 ] [ 17 ]  While degrading harmlessly, it has been shown to possess a functional degradation time of about 30 days  in vivo .  This is much short of the three-to-six month window desired for bioabsorbable stents.  Thus, much attention has been given to drastically reducing the rate of magnesium corrosion by alloying, coating, etc. [ 18 ]  Many novel methods have surfaced to minimize the penetration rate and hydrogen evolution rate (or, in layman's terms, the  corrosion  rate).  One of the most successful has involved the creation of  bioabsorbable metallic glasses  via rapid solidification.  Other, alternative solutions have included the development of magnesium– rare-earth  (Mg-RE) alloys, which benefit from the low  cytotoxicity  of RE elements.  Coatings  and sophisticated materials processing routes are currently being developed to further decrease the corrosion rate. However, a number of issues remain limiting the further development of Mg biomaterials in general. [ 19 ]


Iron  stents were shown using an  in vivo  evaluation method based on the murine abdominal aorta to generate an iron oxide-filled cavity in the vascular wall [ 20 ]  that is unlikely to be metabolized safely. [ 21 ]


Zinc  shows desirable physiological corrosion behavior, meeting a benchmark penetration rate of 20 micrometers per year. [ 22 ]  However, Zn has poor mechanical behavior, with a tensile strength of around 100–150 MPa and an elongation of 0.3–2%, which is far from reaching the strength required as an orthopedic implant or stent material. [ 23 ]


Polymer-based stents have been approved for use in some countries around the world. These are based on poly(L-lactide) ( PLLA ), chosen because it is able to maintain a radially strong scaffold that breaks down over time into lactic acid, a naturally occurring molecule that the body can use for metabolism. Other polymers in development include tyrosine poly carbonate and salicylic acid. [ 24 ]


An example of a naturally dissolving stent is the 'Absorb' stent  'produced by  Abbott [ 25 ]  that has several design components and features:  base scaffold : a poly(L-lactide) polymer similar to that in dissolvable stitches is shaped into a tube made up of zigzag hoops linked together by bridges; drug-eluting layer': a mixture of poly-D, L-lactide (PDLLA) and everolimus; 'markers': a pair of radio-opaque platinum markers at the ends that allow the device to be visualized during angiography; 'delivery system': a balloon delivery system. [ citation needed ]


Recently however, Polymer-based scaffolds, in particular Poly-L-Lactide Acid (PLLA) scaffolds, have raised serious concerns on the scaffold performance particularly in terms of safety which led to the commercial discontinuation of the main representative Absorb. [ 26 ] [ 27 ]


Clinical research has shown that resorbable scaffolds, or naturally dissolving stents, offer comparable efficacy and safety profile to drug-eluting stents. Specifically, the Magmaris resorbable magnesium scaffold [ 28 ]  has reported a favorable safety profile with low target lesion failure and scaffold thrombosis rates. These clinical results are comparable to thin-strutted drug-eluting stents in similar patient populations. [ 29 ] [ 30 ] [ 31 ] [ 32 ]


The Absorb naturally dissolving stent has also been investigated in single-arm trials and in randomized trials comparing it to a  drug-eluting stent . Early and late major adverse cardiac events, revascularizations, and scaffold thromboses have been uncommon and similar to the Xience DES, a market leader in the drug eluting stent category. [ 33 ] [ 34 ] [ 35 ] [ 36 ] [ 37 ]  Studies in real-world patients are ongoing. [ 37 ]


Imaging studies show that the Absorb naturally dissolving stent begins to dissolve from six to 12 months and is fully dissolved between two and three years after it is placed in the artery. [ 35 ]  Two small platinum markers remain to mark the location of the original PCI. The artery is able to dilate and contract, called vasomotion, similar to a healthy blood vessel at two years. [ 34 ]


In the US, the first fully absorbable stent was approved by FDA in 2016. [ 1 ]


3N56 ,  1YK1


NM_001287348 NM_008726


NP_002512 NP_002512


NP_001274277 NP_032752


Brain natriuretic peptide  ( BNP ), also known as  B-type natriuretic peptide , is a  hormone  secreted by  cardiomyocytes  in the  heart ventricles  in response to stretching caused by increased ventricular blood volume. [ 5 ]  BNP is one of the three natriuretic peptides, in addition to atrial natriuretic peptide ( ANP ) and C-type natriuretic peptide (  CNP ). [ 6 ]  BNP was first discovered in porcine brain tissue in 1988, which led to its initial naming as "brain natriuretic peptide", although subsequent research revealed that BNP is primarily produced and secreted by the ventricular myocardium (heart muscle) in response to increased ventricular blood volume and stretching. To reflect its true source, BNP is now often referred to as "B-type natriuretic peptide" while retaining the same acronym.  [ 7 ]


The 32-amino acid polypeptide BNP-32 is secreted attached to a 76–amino acid  N-terminal  fragment in the  prohormone  called  NT-proBNP  (BNPT), which is biologically inactive. Once released, BNP binds to and activates the  atrial natriuretic factor receptor NPRA , and to a lesser extent  NPRB , in a fashion similar to  atrial natriuretic peptide  (ANP) but with 10-fold lower affinity. The  biological half-life  of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing.


The physiologic actions of BNP are similar to those of ANP and include decrease in  systemic   vascular resistance  and  central venous pressure  as well as an increase in  natriuresis . The net effect of these peptides is a decrease in blood pressure due to the decrease in systemic vascular resistance and, thus, afterload. Additionally, the actions of both BNP and ANP result in a decrease in cardiac output due to an overall decrease in central venous pressure and preload as a result of the reduction in blood volume that follows natriuresis and diuresis. [ 8 ]


BNP is synthesized as a 134-amino acid preprohormone (preproBNP), encoded by the human gene NPPB. Removal of the 26-residue N-terminal signal peptide generates the prohormone, proBNP, which is stored intracellularly as an O-linked  glycoprotein ; proBNP is subsequently cleaved between arginine-102 and serine-103 by a specific convertase (probably  furin  or  corin ) into NT-proBNP and the biologically active 32-amino acid polypeptide BNP-32, which are secreted into the blood in equimolar amounts. [ 9 ] [ 10 ]  Cleavage at other sites produces shorter BNP peptides with unknown biological activity. [ 11 ]  Processing of proBNP may be regulated by O-glycosylation of residues near the cleavage sites. [ 12 ]  The synthesis of BNP in cardiomyocytes is stimulated by pro-inflammatory cell factors, such as interleukin-1β, interleukin-6 and tumor necrosis factor-α. [ 13 ]


Relaxes vascular smooth muscle in arterioles and venules by:


Promotes uterine spiral artery remodeling, which is important for preventing pregnancy-induced hypertension. [ 16 ]


BNP and NT-proBNP are measured by  immunoassay . [ 18 ]


A preoperative BNP can be predictive of a risk of an acute cardiac event during vascular surgery.  A  cutoff  of 100 pg/ml has a  sensitivity  of approximately 100%, a  negative predictive value  of approximately 100%, a  specificity  of 90%, and a  positive predictive value  of 78% according to data from the  United Kingdom . [ 23 ]


BNP is cleared by binding to natriuretic peptide receptors (NPRs) and neutral endopeptidase (NEP). Less than 5% of BNP is cleared renally. NT-proBNP is the inactive molecule resulting from cleavage of the prohormone Pro-BNP and is reliant solely on the kidney for excretion. The  achilles heel  of the NT-proBNP molecule is the overlap in kidney disease in the heart failure patient population. [ 24 ] [ 25 ]


Some laboratories report in units ng per Litre (ng/L), which is equivalent to pg/mL


There is a diagnostic 'gray area', often defined as between 100 and 500 pg/mL, for which the test is considered inconclusive, but, in general, levels above 500 pg/ml are considered to be an indicator of heart failure. This so-called gray zone has been addressed in several studies, and using clinical history or other available simple tools can help make the diagnosis. [ 26 ] [ 27 ]


BNP has been suggested as a predictor for a variety of  medical states , including cardiovascular mortality in diabetics [ 28 ]  and cardiac impairment in cancer patients. [ 29 ] [ 30 ]


BNP was found to have an important role in prognostication of heart surgery patients [ 31 ]  and in the emergency department. [ 32 ]  It has been shown that combining BNP with other tools like  impedance cardiography  (ICG) can improve early diagnosis of heart failure and advance prevention strategies. [ 33 ] [ 34 ]  Utility of BNP has also been explored in various settings like  preeclampsia ,  intensive care , shock and  end-stage renal disease  (ESRD). [ 35 ] [ 36 ] [ 37 ]


The effect or race and gender on value of BNP and its utility in that context has been studied extensively. [ 38 ] [ 39 ]


The BNP test is used as an aid in the diagnosis and assessment of severity of heart failure. A recent meta-analysis concerning effects of BNP testing on clinical outcomes of patients presenting to the emergency department with acute dyspnea revealed that BNP testing led to a decrease in admission rates and decrease in mean length of stay, although neither was statistically significant. Effects on all cause hospital mortality was inconclusive. [ 41 ]  The BNP test is also used for the risk stratification of patients with acute coronary syndromes. [ 42 ] [ 43 ]


When interpreting an elevated BNP level, values may be elevated due to factors other than heart failure. Lower levels are often seen in obese patients. [ 44 ]  Higher levels are seen in those with renal disease, in the absence of heart failure.


Recombinant BNP,  nesiritide , has been suggested as a treatment for decompensated heart failure.  However, a clinical trial failed to show a benefit of nesiritide in patients with  acute decompensated heart failure . [ 45 ]  Blockade of  neprilysin , a protease known to degrade members of the natriuretic peptide family, has also been suggested as a possible treatment for heart failure. Dual administration of neprilysin inhibitors and  angiotensin receptor blockers  has been shown to be advantageous to  ACE inhibitors , the current first-line therapy, in multiple settings. [ 46 ] [ 47 ]


attribution : copied from  Brain natriuretic peptide  version as of 13:57, 4 December 2019


Branchial hearts  are accessory pumps that supplement the action of the  systemic heart  in a  cephalopod 's body. They are  myogenic  in nature. [ 1 ]  Branchial hearts are always in pairs located at the base of the  gills . Each branchial heart consists of a single chamber. [ 1 ] [ 2 ]  They pump blood through the gills via the afferent branchial veins. Since they only circulate  venous blood , branchial hearts function under predominantly  anaerobic  conditions. [ 1 ]  Branchial hearts also appear to be involved in  hemocyanin  synthesis. [ 3 ] [ 2 ]


Each branchial heart is directly connected to a branchial heart appendage or pericardial gland. [ 4 ]  The action of the branchial hearts is necessary for the production of primary  urine  in these appendages via pressure filtration. [ 5 ]  Branchial hearts may have evolved from the pericardial glands of  nautiloids , such as those still found in modern  nautiluses . [ 6 ]


This  cephalopod -related article is a  stub . You can help Wikipedia by  expanding it .


The  European Society of CardioVascular Surgery  (ESCVS) is a medical society founded in 1951 in Turin, Italy. Its first president was  René Leriche , first Congress held in Strasbourg in 1952 and its initial members were made up of 40 physicians representing 11 countries in Europe. It is a chapter of the International Society of Angiology, which later became the International Society for Cardiovascular Surgery. [ 1 ] [ 2 ] [ 3 ]


This article about a scientific organization is a  stub . You can help Wikipedia by  expanding it .


The  Broadbent inverted sign  is a  clinical sign  in which pulsation is seen on the postero-lateral wall of the left side of the chest in time with  cardiac systole . This was originally thought to be due to an  aneurysm  of the  left atrium , but is now known to be more commonly associated with  left ventricular hypertrophy . [ 1 ]  The sign is named after  Sir William Broadbent . [ 2 ]


Broadbent sign  is a  clinical sign  in which the 11th and 12th  ribs  are indrawn during systolic phase of a heartbeat, with narrowing of the  intercostal space  posteriorly, which is seen in case  adhesive pericarditis  due to  pericardial  adhesions to the  diaphragm . [ 1 ]


During diseased status of adhesive pericarditis, the pericardium of the heart may adhere not only to the  central tendon of diaphragm , but also to a large area of muscular portion of  diaphragm  as well as anterior chest wall. Thus when the heart contracts, the adhesion portion may be dragged inward and downward (if the main contraction force is toward central tendon of diaphragm). [ 2 ]  Besides, absent palpable apical impulse can also be detected in the case of adhesive pericarditis.


The sign is named after  Walter Broadbent , and was published in his first paper in 1895, although it may have been inspired by his father,  Sir William Broadbent . [ 3 ]


Cannon A waves , or cannon  atrial   waves , are waves seen occasionally in the  jugular vein  of humans with certain  cardiac arrhythmias . When the  atria  and  ventricles  happen to  contract  simultaneously, the  right atrium  contracts against a closed  tricuspid valve , resulting in back pressure into the venous system that can be seen in the  jugular venous pulse  as a high-amplitude "cannon wave". [ 1 ] [ 2 ]  It is associated with heart block, in particular  third-degree (complete) heart block . [ 3 ]  It is also seen in  pulmonary hypertension . [ 3 ]  Cannon A waves may also be seen in  ventricular tachycardia  due to the inherent  AV dissociation  of the arrhythmia. [ citation needed ]


This wave will cause  pulsation  in the neck and abdomen,  headache ,  cough , and  jaw  pain. [ 2 ]


This  cardiovascular system  article is a  stub . You can help Wikipedia by  expanding it .


The  Cardiac Arrest Registry to Enhance Survival  or  CARES  was initiated in 2004 as an agreement between the  Centers for Disease Control and Prevention  and the Department of Emergency Medicine at  Emory University . It is a simple but powerful database that allows cities to collect a small set of performance measures from  9-1-1 ,  first responders ,  fire departments , and  Emergency Medical Services , and link it with outcome data from  hospitals . [ 1 ]  This data enables cities to perform internal benchmarking and improve their response to  cardiac arrest  by strengthening the  chain of  survival  in their community. [ 2 ] [ 3 ]  Because most EMS systems don't measure their response effectively, they are unable to implement change in an effective manner. [ 4 ]  Since the program's inception, survival from cardiac arrest in the city of Atlanta has increased from 3% to 15%. [ 5 ]  For the last half of 2007, survival in Atlanta increased to 31.2%. [ 6 ]


According to the  CDC , the specific objectives of the project are: [ 7 ]


New Castle County, Delaware


The  Cardiac Electrophysiology Society  ( CES ) is an international society of basic and clinical scientists and physicians interested in  cardiac electrophysiology  and  arrhythmias . [ 1 ]  The Cardiac Electrophysiology Society's founder was George Burch in 1949 and its current president is Jonathan C. Makielski, M.D.


This article about a medical organization or association is a  stub . You can help Wikipedia by  expanding it .


The  cardiac nerves  are autonomic nerves which supply the  heart . [ 1 ]  They include:


The nerves go down to the root of the neck with these following association:


Posterior: "prevertebral fascia overlying anterolateral surface of vertebral bodies"


Superior: "common carotid artery"


Inferior: "subclavian artery"


Laterally: "sympathetic trunk" [ 2 ]


This  neuroanatomy  article is a  stub . You can help Wikipedia by  expanding it .


Cardiac psychology  is a specialization of  health psychology  that focuses on the primary and secondary prevention of  heart disease  by incorporating strategies to address the  emotional  and  behavioral  barriers to  lifestyle  changes (e.g.  smoking cessation ), and that seeks to enhance recovery in cardiac patients by means of providing patients tools (e.g. stress management and psychotherapy) to cope with life and physical changes associated with their disease. Cardiac psychologists can help cardiac patients across the lifespan: prevention, pre-surgery, post-surgery, and  rehabilitation  of cardiac disease with a particular emphasis on achieving optimal  quality of life  outcomes.
Cardiac psychology  includes both  research  and  clinical practice  aspects.


The earliest published mention of cardiac psychology in  Western medicine  literature was in 1628 when  William Harvey  wrote that "a mental disturbance provoking pain, excessive joy, hope or anxiety extends to the heart, where it affects temper." [ 1 ]
Research labs have been founded at  Tilburg University ,  Tilburg  Netherlands [ 2 ]  led by  Susanne Pedersen , [ 3 ]  and at  East Carolina University ,  Greenville, North Carolina [ 4 ]  led by  Samuel Sears , [ 5 ]  that focus on psychological aspects of cardiac disease. Cardiac psychology as a term was first used by Robert Allan, PhD, and Stephen Schiedt, MD, as a title of their 1996 book,  Heart and Mind: The Practice of Cardiac Psychology  and launched increased attention to the clinical practice of cardiac psychology. More recently, additional texts, such as  Psychotherapy with Cardiac Patients , (2008) by Ellen Dornelas, [ 6 ]  have attempted to update the literature related to clinical techniques used in the care of cardiac patients. Significant research reviews have also been published spanning psychological factors in cardiac care, [ 7 ] [ 8 ]  implantable electronic medical devices ( pacemaker ,  implantable cardioverter-defibrillator , etc.) [ 9 ] [ 10 ]  and  congestive heart failure . [ 11 ]


Cardiogeriatrics , or  geriatric cardiology , is the branch of  cardiology  and  geriatric medicine  that deals with the cardiovascular disorders in  elderly people .


Cardiac disorders such as  coronary heart disease , including  myocardial infarction ,  heart failure ,  cardiomyopathy , and  arrhythmias  such as  atrial fibrillation , are common and are a major cause of mortality in elderly people. [ 1 ] [ 2 ] [ 3 ]  Vascular disorders such as  atherosclerosis  and  peripheral arterial disease  cause significant morbidity and mortality in aged people. [ 1 ] [ 2 ] [ 3 ]  Guidelines of the Cardiogeriatrics Department of the Brazilian Cardiology Society were published in English. [ 3 ]


The  American Journal of Geriatric Cardiology [ 4 ]  is the official journal of the  Society of Geriatric Cardiology . [ 5 ]


Cardiomyoplasty  is a surgical procedure in which healthy  muscle  from another part of the body is wrapped around the  heart  to provide support for the failing heart. [ 1 ]  Most often the  latissimus dorsi muscle  is used for this purpose. A special pacemaker is implanted to make the skeletal muscle contract. If cardiomyoplasty is successful and increased cardiac output is achieved, it usually acts as a bridging therapy, giving time for damaged  myocardium  to be treated in other ways, such as remodeling by cellular therapies. [ 2 ] [ 3 ]


Cellular cardiomyoplasty  is a method which augments myocardial function and cardiac output by directly growing new muscle cells in the damaged myocardium (heart muscle). Tissue engineering, which is now being categorized as a form of regenerative medicine, can be defined as biomedical engineering to reconstruct, repair, and improve biological tissues. Research efforts in tissue engineering have been ongoing and it is emerging as one of the key areas of medical research. Furthermore, there are vast developments in tissue engineering, which involve leveraging of technologies from biomaterials, molecular medicine, biochemistry, nanotechnology, genetic and biomedical engineering for regeneration and cell expansion targets to restructure and/or repair human organs. Injection of cardiomyogenic and/or angiogenic stem cells have been proposed as alternatives to existing treatments. For cardiovascular application, skeletal myoblasts are of great interest as they can be easily isolated and are associated with high proliferation rate. These cells have also been demonstrated to be  hypoxia -resistant.


Bone marrow contains different cell populations, which exhibit excellent plasticity toward cardiogenic and endothelial cells. These cell populations are endothelial progenitor cells, hematopoietic stem cells and mesenchymal stem cells.  Adipose tissue host progenitor cells with reported interesting cardiomyogenic and vasculogenic potential in the sense that they improve heart functions and reduce infarction size in rodent animal models.  Subcutaneous adipose tissue is also a source of mesenchymal stem cells and have demonstrated positive outcomes in terms of cardiovascular tissue remodeling. Mammal hearts also host naturally occurring cardiac stem cells which may be capable of differentiating themselves into cardiomyocytes, endothelial cells and cardiac fibroblasts. [ 4 ]  This self-regeneration capacity gives rise to alternatives to classical cellular therapies whereby administration of growth factors such as Thymosin β4 for cell activation and migration are solely necessary. Largely democratized in terms of population information, embryonic stem cells are known for their strong capacity for expansion and differentiation into cardiomyocytes, endothelial cells and cardiac fibroblasts.


However, if non autologous, immunosuppression therapy is associated with such treatment. Hence, research has been focused on induced pluripotent stem cells (iPSCs) from somatic human tissue. Further to cell and necessary relevant growth factor selection, cell delivery is an important issue.  Indeed, the intracoronary route is the most straightforward cell delivery route as associated with intramyocardial cellular retention; retention rates are however low, i.e. exceed 10%. Washed off cells reach other organs or die, which can be an issue at the time of prepare ICH module 8. Other alternative injection routes have been studied, namely injection  via sternotomy, endomyocardial  and intracoronary routes. Nevertheless, all methods aforementioned have been associated with limited cardiac function improvements and limited cell survival once implanted in the fibrous myocardium.


To resume, stem cells and delivery routes aforementioned are suitable for cardiomyoplasty as demonstrated safe with some degree of benefit for the patient. However, cardiac remodelling remains limited due to limited cell residency, impact of mechanical forces onto cell survival and tissue hypoxia. Furthermore, lack of cellular electrochemical coupling can lead to arrhythmias. Another point of consideration concerns the use of embryonic stem cells, whereby indifferentiation yields uncontrolled proliferation and possible consequent formation of teratomas. Also iPSCs have been associated with viral infection and eventual oncogenicity. Cardiac tissue engineering is a new technology based on the use of combinations of cells with regenerative capacity, biological and/or synthetic materials, cell signaling agents to induce the regeneration of an organ or damaged tissue. In an ideal scenario, regenerated tissue would reproduce sophisticated asymmetric helicodoidal architecture of the myocardium with the production of specialized extracellular matrix to stimulate vascularization in the implanted tissue. From a cellular perspective, [ 5 ]  available techniques are monolayer cell construct onto temperature-sensitive polymer, where their detachment is driven by behavior of the mechanical properties of the synthetic support without the need of any enzymatic digestion such as trypsin. Cardiomyocites sheets have also been successfully implanted with an observed contractile function as a result of inter-cellular communication between the host and graft. However, from a practical point of view, such approach lacks of translational character as all studies share the lack of reproducibility, i.e. a construct of similar characteristics of the native tissue does not guarantee the same results. Another approach resides in the use of hydrogels. Natural hydrogels such as Matrigel, [ 6 ]  collagen and fibrin have been used as entrapment matrices, wherein the cells to be injected are embedded. However the associated high pressure of injection is associated with a high mortality rate for the cells thereby negatively impacting the benefit ratio of this approach. Furthermore, from a technical point of view, due to the polydispersity of these natural hydrogels, purification is a requisite but very difficult step. Synthetic hydrogels, such as  polyethylene glycol , polylactic acid, polylactic acid-co-glycolic acid, polycaprolactone, polyacrylamide and polyurethane have been proposed.  Metalloproteinase-sensitive polyethylene is of particular interest. Indeed, this polymer modulates its mechanical and biophysical properties accordingly to enzymatic activities associated with cardiomyogenic differentiation of implanted cells. To date, no hydrogel matrix is FDA-approved for stem cell therapy use despite a large number of biomaterials currently commercially available.


A general comment on hydrogel based technologies:


Natural hydrogel are well tolerated by the host and cells due to their mimicking the natural ECM in terms of backbone and microstructure. However they suffer from batch to batch variation (a drawback for current Good Manufacturing Practices (cGMPs) required for clinical application), high degradation rates, and poor tenability. Synthetic hydrogels are reproducible, tunable and amenable regulatory and manufacturing protocols. [ 7 ] [ 8 ] [ 9 ]  Their chemical modification permits the integration of cellular attachment sites and a certain control over degradation rates. Semi-synthetic hydrogels share characteristics of both classes. Indeed, they permit either the modification of the purified natural biopolymers or by coupling the synthetic component with integrin and/or growth factor binding sites.


A frequent type of syncope, termed  vasovagal syncope  is originated by intense cardioinhibition, mediated by a sudden  vagal  reflex, that causes transitory  cardiac arrest  by  asystole  and/or transient total  atrioventricular block . [ 1 ] [ 2 ]  It is known as “Vaso-vagal Syncope”, “Neurocardiogenic Syncope” or “Neurally-mediated Reflex Syncope”. [ 3 ]  Although many different therapies have been tried in this condition, severe and refractory cases have been treated with  pacemaker  implantation despite great controversies about its benefit. [ 4 ] [ 5 ]


The “ Cardioneuroablation ” is a technique created in the nineties and patented in  USA , aiming to eliminate the cardiac branch of vagal reflex in order to treat the neurocardiogenic syncope without pacemaker implantation. [ 6 ] [ 7 ]  It is performed without  surgery , by using  radiofrequency   catheter ablation  with one-day hospital. [ citation needed ]


The results up to 100 months follow-up are showing better outcome than clinical measures or pacemaker implantation with changing the tilt-test on to normal and by absence of syncope in more than 90% of patients without medications. [ 8 ] [ 9 ]


Cardiooncology ,  cardio-oncology  or  cardiovascular oncology  is an interdisciplinary field of  medicine  which study the molecular and clinical alterations in  cardiovascular system  during the different methods of  treatment of cancer , especially  chemotherapy  and  targeted therapy . [ 1 ]


Since 2018 the  European Society of Cardiology  has had a council of cardio-oncology. [ 2 ]


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:


A  cardiovascular technician , also known as a  vascular technician , is health professional that deal with the  circulatory system .


Technicians who use  ultrasound  to examine the  heart chambers ,  valves , and  vessels  are referred to as cardiac sonographers. [ 1 ]  They use ultrasound instrumentation to create images called echocardiograms. An  echocardiogram  may be performed while the patient is either resting or physically active. Technicians may administer medication to physically active patients to assess their heart function. Cardiac sonographers also may assist  transesophageal echocardiography , which involves placing a tube in the patient's  esophagus  to obtain ultrasound images. [ citation needed ]


Those who assist in the diagnosis of disorders affecting the circulation are known as vascular technologist, vascular specialists or vascular sonographers. They obtain a medical history, evaluate pulses and assess blood flow in arteries and veins by listening to the vascular flow sounds for abnormalities. Then they perform a  noninvasive  procedure using ultrasound instrumentation to record vascular information such as vascular blood flow,  blood pressure , changes in limb volume,  oxygen saturation ,  cerebral circulation , peripheral circulation, and abdominal circulation. Many of these tests are performed during or immediately after surgery.


Cardiovascular  technicians who obtain EKGs are known as electrocardiograph (or EKG) technicians. To take a basic  EKG , which traces electrical impulses transmitted by the heart, technicians attach  electrodes  to the patient's chest, arms, and legs, and then manipulate switches on an EKG machine to obtain a reading. An EKG is printed out for interpretation by the physician. This test is done before most kinds of surgery or as part of a routine physical examination, especially on persons who have reached middle age or who have a history of cardiovascular problems.


EKG technicians with advanced training setup Holter monitor and stress testing. For Holter monitoring, technicians place electrodes on the patient's chest and attach a portable EKG monitor to the patient's belt. Following 24 or more hours of normal activity by the patient, the technician removes a tape from the monitor and places it in a scanner. After checking the quality of the recorded impulses on an electronic screen, the technician usually prints the information from the tape for analysis by a physician. Physicians use the output from the scanner to diagnose heart ailments, such as heart rhythm abnormalities or problems with  pacemakers .


For a treadmill stress test, EKG technicians document the patient's medical history, explain the procedure, connect the patient to an EKG monitor, and obtain a baseline reading and resting blood pressure. Next, they monitor the heart's performance while the patient is walking on a treadmill, gradually increasing the treadmill's speed to observe the effect of increased exertion.


The position is generally unlicensed and skills are learned on the job; however, two- and four-year training programs to learn advanced ECG technical skills are available at junior colleges and community colleges. [ 2 ]


Carney complex  and its subsets  LAMB syndrome [ 1 ]  and  NAME syndrome [ 1 ]  are  autosomal dominant  conditions comprising  myxomas  of the heart and skin, hyperpigmentation of the skin ( lentiginosis ), and  endocrine  overactivity. [ 2 ] [ 3 ]  It is distinct from  Carney's triad . Approximately 7% of all cardiac myxomas are associated with Carney complex. [ 4 ]


The spotty skin pigmentation and lentigines occur most commonly on the face, especially on the lips, eyelids,  conjunctiva  and oral mucosa. [ 3 ]   Cardiac myxomas  may lead to  embolic strokes  and  heart failure [ 4 ]  and may present with fever, joint pain, shortness of breath, diastolic rumble and tumor plop. Myxomas may also occur outside the heart, usually in the skin and breast. Endocrine tumors may manifest as disorders such as  Cushing syndrome . The most common  endocrine gland  manifestation is an ACTH-independent Cushing's syndrome due to  primary pigmented nodular adrenocortical disease  (PPNAD). [ 5 ]


The LAMB  acronym  refers to  lentigines ,  atrial   myxomas , and  blue nevi . [ 1 ]  NAME refers to  nevi , atrial myxoma, myxoid neurofibromas, and  ephelides . [ 1 ]


Testicular cancer, particularly  Sertoli cell  type, is associated with Carney syndrome. [ 7 ]  Thyroid and pancreas cancer may also occur. [ 8 ] [ 9 ]


Although  J Aidan Carney  also described  Carney's triad  it is entirely different. [ 10 ]


Carney complex is most commonly caused by mutations in the  PRKAR1A  gene on  chromosome 17  (17q23-q24) [ 11 ]
which may function as a  tumor-suppressor gene . The encoded protein is a type 1A regulatory subunit of protein kinase A. Inactivating  germline mutations  of this gene are found in 70% of people with Carney complex. [ 12 ]


Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at  chromosome 2  (2p16). [ 13 ] [ 14 ]


Both types of Carney complex are  autosomal dominant . Despite dissimilar genetics, there appears to be no  phenotypic  difference between PRKAR1A and chromosome 2p16 mutations. [ 13 ]


Cardiac myxomas can be difficult to manage surgically because of recurrence within the heart, often far away from the site of the initial tumor. [ 3 ] [ 4 ]


In 1914 an American neurosurgeon,  Harvey Cushing , reported on a patient with a pituitary tumour on whom he had operated. The post mortem findings as reported were consistent with Carney complex, though at the time this condition had yet to be described. In 2017 archived tissue from the operation in Cushing's report was subjected to DNA sequencing, revealing an Arg74His ( arginine  to  histidine :  guanine  (G)->  adenosine  (A)  transition  in the second  codon  position of the 74th codon in the protein) mutation in the PRKAR1A gene, confirming a diagnosis of Carney complex. Therefore, Cushing's paper appears to be the first report of this complex. [ 15 ]


The  central  governor  is a proposed process in the brain that regulates exercise in regard to a neurally calculated safe  exertion by the body. In particular, physical activity is controlled so that its intensity cannot threaten the body’s  homeostasis  by causing  anoxic  damage to the  heart muscle . The central governor limits exercise by reducing the neural recruitment of muscle fibers. This reduced recruitment causes the sensation of  fatigue . The existence of a central governor was suggested to explain fatigue after prolonged strenuous exercise in long-distance running and other endurance sports, but its ideas could also apply to other causes of exertion-induced fatigue.


The existence of a central governor was proposed by  Tim Noakes  in 1997, but a similar idea was suggested in 1924 by  Archibald Hill . It was first published as a full theory by Tim Noakes, Alan St Clair Gibson and Vicki Lambert in five linked articles in the British Journal of Sports Medicine in 2004-2005 [ 1 ]


In contrast to this idea is the one that fatigue is due to peripheral "limitation" or "catastrophe." In this view, regulation by fatigue occurs as a consequence of a failure of homeostasis directly in muscles.


The 1922  Nobel Prize in Physiology or Medicine  winner  Archibald Hill  proposed in 1924 that the heart was protected from anoxia in strenuous exercise by the existence of a governor.


the heart is able to regulate its output, to some extent, in accordance with the degree of saturation of the arterial blood ... we suggest that, in the body (either in the heart muscle itself or in the nervous system), there is some mechanism which causes a slowing of the circulation as soon as a serious degree of unsaturation occurs, and  vice versa . This mechanism would tend, to some degree, to act as a ‘governor’, maintaining a reasonably high degree of saturation of the blood: the breathing of a gas mixture rich in oxygen would produce a greater degree of saturation of the blood and so allow the output to increase until the ‘governor’ stopped it again. We realise the danger of a hypothesis partly suggested by teleological reasoning: in this case, however, we can see no other explanation of our experimental results pp. 163 [ 2 ]


This hypothesis was disregarded and further research upon exercise fatigue was modeled in terms of it being due to a mechanical failure of the exercising muscles ("peripheral muscle fatigue"). This failure was caused either by an inadequate oxygen supply to the exercising muscles, lactic acid buildup, or total energy depletion in the exhausted muscles. [ 3 ]


Tim Noakes , a professor of exercise and sports science at the  University of Cape Town , in 1997 [ 4 ]  has renewed Hill’s argument on the basis of modern research. Along with collaborators Alan St Clair Gibson and Vicki Lambert, they suggested that the power output by muscles during exercise is continuously adjusted in regard to calculations made by the brain in regard to a safe level of exertion. These neural calculations factor in earlier experience with strenuous exercise, the planning duration of the exercise, and the present metabolic state of the body. These brain models [ 5 ]  ensure that body homeostasis is protected, and an emergency reserve margin is maintained. [ 6 ] [ 7 ] [ 8 ] [ 9 ]  This neural control adjusts the number of activated skeletal muscle motor units, a control which is subjectively experienced as  fatigue . This process, though occurring in the brain, is outside conscious control.


the rising perception of discomfort produced by exhausting exercise progressively reduces the conscious desire to over-ride this control mechanism, which, if it were to be reduced, would lead to the recruitment of more motor units. Thus the presence of conscious over-ride would be undesirable because it would increase or maintain the exercise intensity, thereby threatening homoeostasis ... as exercise performance is centrally regulated by the CNS, then fatigue should no longer be considered a physical event but rather a sensation or emotion, separate from an overt physical manifestation—for example, the reduction in force output by the active muscles. Rather we now suggest that the physical manifestation of any increasing perception of fatigue may simply be an alteration in the subconsciously regulated pace at which the exercise is performed. Hence the novel suggestion is that the conventional understanding of fatigue is flawed because it makes no distinction between the sensation itself and the physical expression of that sensation which, we suggest, is the alteration in the subconsciously regulated pacing strategy consequent on changing motor unit recruitment/derecruitment by the CNS. [ 10 ]


Noakes, St Clair Gibson and Lambert created the idea of the central governor in the context of prolonged endurance exercise. However, they have noted that the central processes involved might also underlie the existence of other kinds of fatigue:


This new interpretation is the first to allow a more reasonable description of a number of phenomena that defy rational explanation according to the traditional ‘‘limitations’’ models of fatigue. These include, among many others, the chronic fatigue syndrome, in which affected individuals experience evident fatigue at rest, and the role of psychological and motivational factors,  centrally (brain) acting pharmaceutical agents,  hypnosis, shouting or sudden unexpected gunshots,  or other forms of distraction including music or premeditated deception on human exercise performance. [ 11 ]


In support of this, placebos (which must be mediated by a central process) have a powerful effect upon not only fatigue in prolonged exercise, [ 12 ] [ 13 ]  but also upon short term endurance exercise such as sprint speed, [ 14 ]  the maximum weight that could be lifted with leg extension, [ 15 ]  and the tolerance of  ischemic  pain and power when a tourniqueted hand squeezes a spring exerciser 12 times. [ 16 ]


The existence of a central governor over physiology has been questioned since ‘physiological catastrophes’ can and do occur in athletes (important examples in  marathons  have been  Dorando Pietri ,  Jim Peters  and  Gabriela Andersen-Schiess ). This suggests that humans can over-ride ‘the central governor’. [ 17 ]  Moreover, a variety of peripheral factors in addition to those such as lactic acid build up can impair muscle power and might act to protect against "catastrophe". [ 18 ]  Another objection is that models incorporating conscious control also provide an alternative explanation  [ 19 ]  (see Noakes’ reply). [ 20 ]


Exercise fatigue has also been attributed to the direct effects of exercise upon the brain such as increased cerebral levels of  serotonin , reduced level of  glutamate  secondary to uptake of ammonia in the brain, brain hyperthermia, and  glycogen  depletion in brain cells. [ 21 ] [ 22 ]


Cerebral circulation  is the movement of  blood  through a network of  cerebral arteries  and  veins  supplying the  brain . The rate of cerebral  blood flow  in an adult  human  is typically 750  milliliters  per  minute , or about 15% of  cardiac output .  Arteries  deliver  oxygenated  blood,  glucose  and other nutrients to the brain.  Veins  carry "used or spent" blood back to the  heart , to remove  carbon dioxide ,  lactic acid , and other  metabolic  products. The  neurovascular unit  regulates cerebral blood flow so that activated neurons can be supplied with energy in the right amount and at the right time. [ 1 ]  Because the  brain  would quickly suffer damage from any stoppage in blood supply, the cerebral circulatory system has safeguards including  autoregulation  of the  blood vessels . The failure of these safeguards may result in a  stroke . The  volume  of blood in circulation is called the  cerebral blood flow . Sudden intense accelerations change the  gravitational forces  perceived by bodies and can severely  impair cerebral circulation  and normal functions to the point of becoming serious life-threatening conditions.


The following description is based on idealized human cerebral circulation. The pattern of circulation and its  nomenclature  vary between organisms.


Blood supply to the brain is normally divided into anterior and posterior segments, relating to the different arteries that supply the brain. The two main pairs of arteries are the  internal carotid arteries  (supply the anterior brain) and  vertebral arteries  (supplying the  brainstem  and posterior brain). [ 2 ]  The anterior and posterior cerebral circulations are interconnected via bilateral  posterior communicating arteries . They are part of the  circle of Willis , which provides backup circulation to the brain. In case one of the supply arteries is occluded, the circle of Willis provides interconnections between the anterior and the posterior cerebral circulation along the floor of the cerebral vault, providing blood to tissues that would otherwise become  ischemic . [ 3 ]


The  anterior  cerebral circulation  is the blood supply to the anterior portion of the brain including  eyes . It is supplied by the following arteries:


The  posterior cerebral circulation  is the blood supply to the posterior portion of the brain, including the  occipital lobes ,  cerebellum  and  brainstem .
It is supplied by the following arteries:


The venous drainage of the cerebrum can be separated into two subdivisions:  superficial and deep.


The superficial system is composed of  dural venous sinuses ,  sinuses  (channels) within the  dura mater . The dural sinuses are therefore located on the surface of the cerebrum.  The most prominent of these sinuses is the  superior sagittal sinus  which is located in the sagittal plane under the midline of the cerebral vault, posteriorly and inferiorly to the  confluence of sinuses , where the superficial drainage joins with the sinus that primarily drains the deep venous system.  From here, two  transverse sinuses  bifurcate and travel laterally and inferiorly in an S-shaped curve that forms the  sigmoid sinuses  which go on to form the two  jugular veins . In the neck, the  jugular veins  parallel the upward course of the  carotid arteries  and drain blood into the  superior vena cava . The veins puncture the relevant dural sinus, piercing the arachnoid and dura mater as  bridging veins  that drain their contents into the sinus. [ 5 ]


The deep venous system is primarily composed of traditional  veins  inside the deep structures of the brain, which join behind the midbrain to form the  great cerebral vein  (vein of Galen).  This vein merges with the  inferior sagittal sinus  to form the  straight sinus  which then joins the superficial venous system mentioned above at the  confluence of sinuses .


The maturation of blood vessels in the brain is a  critical process  that occurs postnatally. [ 6 ]  It involves the acquisition of key barrier and contractile properties essential for brain function. During the early postnatal phase,  endothelial cells  (ECs) and  vascular smooth muscle cells  (VSMCs) undergo significant molecular and functional changes.


Endothelial cells begin to express  P-glycoprotein , a crucial  efflux transporter  that helps protect the brain by expelling harmful substances. [ 7 ]  This efflux capacity is progressively acquired and becomes fully functional by the postnatal period. Additionally, VSMCs, which initially populate the arterial network, start to express contractile proteins such as smooth muscle  actin  (SMA) and  myosin-11 , transforming VSMCs into contractile cells capable of regulating blood vessel tone and cerebral blood flow.


The expression of Myh11 in VSMCs acts as a developmental switch, with significant upregulation occurring from birth to the age of 2 to 5 years. [ 6 ]  This is a critical period needed for the establishment of vessel contractility and the overall functionality of the cerebral circulation.


Cerebral blood flow  (CBF) is the blood supply to the  brain  in a given period of time. [ 8 ]  In an adult, CBF is typically 750 millilitres per minute or 15.8 ± 5.7% of the  cardiac output . [ 9 ]  This equates to an average  perfusion  of 50 to 54 millilitres of blood per 100 grams of brain tissue per minute. [ 10 ] [ 11 ] [ 12 ]


The radio index of cerebral blood flow/cardiac output (CCRI) decreases by 1.3% per decade, even though cardiac output remains unchanged. [ 9 ]  Across the adult lifespan, women have a higher CCRI than men. [ 9 ]  CBF is inversely associated with  body mass index . [ 9 ]


CBF is tightly regulated to meet the brain's  metabolic  demands. [ 10 ] [ 13 ]  Too much blood (a clinical condition of a normal homeostatic response of  hyperemia ) [ 1 ]  can raise  intracranial pressure  (ICP), which can compress and damage delicate brain tissue. Too little blood flow ( ischemia ) results if blood flow to the brain is below 18 to 20 ml per 100 g per minute, and tissue death occurs if flow dips below 8 to 10 ml per 100 g per minute. In brain tissue, a  biochemical cascade  known as the  ischemic cascade  is triggered when the tissue becomes ischemic, potentially resulting in damage to and the death of  brain cells . Medical professionals must take steps to maintain proper CBF in patients who have conditions like  shock ,  stroke ,  cerebral edema , and  traumatic brain injury .


Cerebral blood flow is determined by a number of factors, such as  viscosity  of blood, how dilated  blood vessels  are, and the net pressure of the flow of blood into the brain, known as  cerebral perfusion pressure , which is determined by the body's  blood pressure . Cerebral perfusion pressure (CPP) is defined as the mean arterial pressure (MAP) minus the intracranial pressure (ICP). In normal individuals, it should be above 50 mm Hg. Intracranial pressure should not be above 15 mm Hg (ICP of 20 mm Hg is considered as intracranial hypertension). [ 14 ]  Cerebral blood vessels are able to change the flow of blood through them by altering their diameters in a process called  cerebral autoregulation ; they constrict when systemic blood pressure is raised and dilate when it is lowered. [ 15 ]  Arterioles also constrict and dilate in response to different chemical concentrations. For example, they dilate in response to higher levels of  carbon dioxide  in the blood and constrict in response to lower levels of carbon dioxide. [ 15 ]


For example, assuming a person with an arterial partial pressure of carbon dioxide ( PaCO2 ) of 40 mmHg (normal range of 38–42 mmHg) [ 16 ]  and a CBF of 50 ml per 100g per min. If the PaCO2 dips to 30 mmHg, this represents a 10 mmHg decrease from the initial value of PaCO2. Consequently, the CBF decreases by 1ml per 100g per min for each 1mmHg decrease in PaCO2, resulting in a new CBF of 40ml per 100g of brain tissue per minute. In fact, for each 1 mmHg increase or decrease in PaCO2, between the range of 20–60 mmHg, there is a corresponding CBF change in the same direction of approximately 1–2 ml/100g/min, or 2–5% of the CBF value. [ 17 ]  This is why small alterations in respiration pattern can cause significant changes in global CBF, specially through PaCO2 variations. [ 17 ]


CBF is equal to the  cerebral perfusion pressure  (CPP) divided by the cerebrovascular resistance (CVR): [ 18 ]


Control of CBF is considered in terms of the factors affecting CPP and the factors affecting CVR. CVR is controlled by four major mechanisms:


Increased  intracranial pressure  (ICP) causes decreased blood perfusion of  brain cells  by mainly two mechanisms:


Cerebral perfusion pressure is the net  pressure  gradient causing  cerebral blood flow  to the brain (brain  perfusion ).  It must be maintained within narrow limits; too little pressure could cause brain tissue to become  ischemic  (having inadequate blood flow), and too much could raise  intracranial pressure .


Arterial spin labeling  (ASL),  phase contrast magnetic resonance imaging  (PC-MRI), and  positron emission tomography  (PET) are  neuroimaging  techniques that can be used to measure CBF. ASL and PET can also be used to measure regional CBF (rCBF) within a specific brain region.
rCBF at one location can be measured over time by  thermal diffusion [ 19 ]


ocular group:   central retinal


The  chain of survival  refers to a series of actions that, properly executed, reduce the mortality associated with  sudden cardiac arrest . Like any chain, the chain of survival is only as strong as its weakest link. [ 1 ] [ 2 ]  The six interdependent links in the chain of survival are early recognition of sudden cardiac arrest and access to emergency medical care, [ 3 ]  early  CPR , early defibrillation, early  advanced cardiac life support , and physical and emotional recovery. The first three links in the chain can be performed by lay bystanders, while the second three links are designated to medical professionals. [ 4 ]  Currently, between 70 and 90% of cardiac arrest patients die before they reach the hospital. [ 4 ]  However, a cardiac arrest does not have to be lethal if bystanders can take the right steps immediately. [ 4 ]


According to the American Heart Association, out-of-hospital cardiac arrest can affect more than 300,000 people in the United States each year. [ 5 ]  Three minutes after the onset of cardiac arrest, a lack of blood flow starts to damage the brain, and 10 minutes after, the chances of survival are low. [ 6 ]  Therefore, bystanders have only a few minutes to act to optimize a person's chances of survival and recovery. [ citation needed ]


To improve survival outcomes for people who have experienced out-of-hospital cardiac arrest, the American Heart Association–International Liaison Committee on Resuscitation recommended the chain of survival concept in the early 2000s. [ 3 ]  Originally, the chain consisted of four steps: early access to emergency medical care was the first link, the second link was early CPR, early defibrillation was the third link, and the final link was early advanced cardiac life support. [ 3 ]  Over the years, the American Heart Association has added two new links to the chain: post-resuscitation care in 2010, [ 7 ] [ 3 ]  and physical and emotional recovery in 2020. [ 4 ]  Also in 2020, the American Heart Association issued a new pediatric chain of survival for infants, children, and adolescents. [ 8 ]


Mary M. Newman, co-founder and president/CEO of the Sudden Cardiac Arrest (SCA) Foundation and previous executive director of the National Center for Early Defibrillation at the University of Pittsburgh, [ 9 ]  developed the chain of survival metaphor and first described it  [ 6 ]  in an article she wrote for the  Journal of Emergency Medical Services  in 1989, [ 10 ]  and further promoted in an editorial she wrote for the first issue of  Currents in Emergency Cardiac Care  in 1990. [ 11 ]  The American Heart Association later adopted the concept and elaborated on it in its 1992 guidelines for  cardiopulmonary resuscitation  and emergency cardiac care, [ 12 ] [ 13 ]  The International Liaison Committee on Resuscitation (ILCOR) echoed the concept in 1997. [ 1 ]  The links of the Chain of survival are described below.


Ideally, someone must recognize an impending cardiac arrest or otherwise witness the cardiac arrest and activate the  EMS system  as early as possible with an immediate call to the emergency services. Unfortunately, many persons experiencing symptoms (for example, angina) that may lead to a cardiac arrest ignore these warning symptoms or, recognizing these warning symptoms correctly, fail to activate the EMS system, preferring to contact relatives instead (e.g., the elderly often contact their adult offspring rather than contact emergency services). [ citation needed ]


To be most effective, bystanders should provide CPR immediately after a patient collapses. In their  2015 guidelines , the American Heart Association re-emphasized the importance of more bystanders performing hands-only CPR until EMS personnel arrive because, at present, fewer than 40% of people who have an out-of-hospital cardiac arrest receive CPR from a bystander. [ 4 ]  The guidelines recommend lay rescuers start CPR on a person with presumed cardiac arrest because the overall risk of harm to patients from CPR is low, even if their heart hasn't stopped beating. [ 4 ]  Properly performed CPR can keep the heart in a shockable rhythm for 10–12 minutes longer. [ citation needed ]


Most adults who can be saved from cardiac arrest are in  ventricular fibrillation  or pulseless  ventricular tachycardia , which means their heart has fallen out of rhythm. [ 14 ]  Early defibrillation is the link in the chain most likely to improve survival since defibrillation can help shock the heart back into a regular beat. [ 15 ]  Early, rapid defibrillation is considered the most important link in the chain of survival. [ 15 ]  Rapid defibrillation outside of the hospital improves the chances of survival by as much as 30%, and involves using an automated external defibrillator (AED) to shock the patient's heart. [ 16 ]


While CPR keeps blood flowing artificially, [ 17 ]  rapid defibrillation is the only way to restart the heart and reset it to a healthy rhythm. [ 18 ]  And while only 40% of adults experiencing cardiac arrest receive CPR, fewer than 12% receive shocks from an AED before EMS arrival. [ 8 ]  What is more, the chances of the patient's survival decrease by as much as 10% with every minute that they do not receive rapid defibrillation. [ 19 ]


AEDs are becoming more common in businesses, schools, and even the home as the public becomes more aware of the importance of rapid defibrillation. [ 20 ] [ 6 ]  AEDs come with pre-recorded instructions and are easy to use. [ 18 ]  If an AED is not available, bystanders will need to continue CPR until emergency responders arrive with a defibrillator, which is why it is important to recognize cardiac arrest and call for help quickly. [ 21 ] [ 6 ]


Public access defibrillation may be the key to improving survival rates in out-of-hospital cardiac arrest, [ 1 ]  but is of the greatest value when the other links in the chain do not fail.


Early  advanced cardiac life support  by paramedics is another critical link in the chain of survival. In communities with survival rates > 20%, a minimum of two of the rescuers are trained to the advanced level. [ citation needed ]


Some ACLS ambulance providers will administer medications to manage pain, arrhythmias, shock, and pulmonary congestion; monitor the heart rhythm to identify any potentially lethal cardiac arrhythmias; or initiate transcutaneous pacing. [ 15 ]  ACLS ambulance providers use the mnemonic "MONA" (morphine, oxygen, nitroglycerin, and aspirin) to reflect the out-of-hospital therapies they will use for cardiac arrest. [ 15 ]


Often, ACLS ambulance providers will attach an electrocardiogram to the patient and transmit its findings to the receiving hospital or care facility, which leads to earlier diagnosis of a heart attack, and significantly reduces time to treatment at the hospital. [ 15 ]  This prearrival ECG and notification has been shown to improve patient outcomes. [ 15 ]  In the event of a complication at the scene of the event or on the way to the hospital, ACLS ambulance providers can administer life saving therapies, including CPR, rapid defibrillation, airway management, and intravenous medications. [ 15 ]


In October 2020, the American Heart Association added the recovery phase as the sixth link in the chain of survival. [ 4 ]  Recovery consists of cardiac arrest survivors receiving treatment, surveillance, and rehabilitation at a hospital. [ 4 ]  It also includes an assessment for anxiety, depression, and post-traumatic stress, which can all lead to future repeated events. Before being discharged from the hospital, the American Heart Association recommends that cardiac arrest survivors receive rehabilitation assessment and treatment for physical, neurologic, cardiopulmonary, and cognitive impairments. [ 4 ] [ 8 ]  They also recommend that cardiac arrest survivors and their caregivers receive comprehensive, multidisciplinary discharge planning to include medical and rehabilitative treatment recommendations and return to activity and work expectations. [ 4 ] [ 8 ]


A patient's recovery from cardiac arrest continues long after their initial hospitalization following the event, so the American Heart Association recommended in their 2020 guidelines that patients have formal assessment and support for their physical, cognitive, and psychosocial needs. [ 8 ]


Computer-aided auscultation  ( CAA ), or  computerized assisted auscultation , is a digital form of  auscultation . It includes the recording, visualization, storage, analysis and sharing of  digital recordings  of heart or lung sounds. The recordings are obtained using an electronic stethoscope or similarly suitable recording device.
Computer-aided auscultation is designed to assist health care professionals who perform auscultation as part of their diagnostic process. Commercial CAA products are usually classified as  clinical decision support systems  that support medical professionals in making a diagnosis. As such they are medical devices and require certification or approval from a competent authority (e.g.  FDA  approval,  CE conformity  issued by notified body).


Compared to traditional auscultation, computer-aided auscultation (CAA) offers a range of improvements beneficial to multiple stakeholders:


In a CAA system, sounds are recorded through an electronic stethoscope. The audio data is transferred to an electronic device via  Bluetooth  or an audio cable connection. Special software on that device visualizes, stores and analyzes the data. With some of the more sophisticated CAA systems, the CAA analysis yields results that can be used to objectify diagnoses ( decision support system ). [ citation needed ]


The components of a CAA system depend on its complexity. Whereas some of the simpler systems provide only visualization or storage options, other systems combine visualization, storage, analysis and the ability to electronically manage said data.


Electronic stethoscopes  (also digital stethoscopes) convert acoustic sound waves into digital electrical signals. These signals are then amplified by means of transducers and currently reach levels up to 100 times higher than traditional acoustic stethoscopes. Additionally, electronic stethoscopes can be used to filter out background noise, a feature that can be safety-relevant and facilitate more accurate diagnoses. Whereas sound amplification and filtering are the main functions of an electronic stethoscope, the ability to access the sounds through external means via Bluetooth or audio cables makes them an ideal sound-capturing device for CAA systems. [ citation needed ]


Devices that can be used to connect to an electronic stethoscope and record the audio signal (e.g. heart or lung sounds) include PC, laptop and mobile devices like smartphones or tablets. Generally, CAA systems include software that can visualize the incoming audio signal. More sophisticated CAA systems include live noise detection algorithms, designed to help the user achieve the best possible recording quality.


A key feature of CAA systems is the automated analysis of the recorded audio signals by signal processing algorithms. Such algorithms can run directly on the device used for making the recording, or be hosted in a cloud connected to the device. The degree of autonomy of currently available analysis algorithms varies greatly. While some systems operate fully autonomously, [ 7 ]  early PC-based systems required significant user interaction and interpretation of results, [ 8 ]  and other analysis systems require some degree of assistance by the user like manual confirmation/correction of estimated heart rates. [ 9 ]


Recorded sounds and associated analytical and patient data can be electronically stored, managed or archived. Patient identifying information might be handled or stored in the process. If the stored data classifies as PHI (protected health information), a system hosting such data must be compliant with country-specific data protection laws like  HIPAA  for the US or the  Data Protection Directive  for the EU. Storage options for current CAA systems range from the basic ability to retrieve a downloadable PDF report to a comprehensive cloud-based interface for electronic management of all auscultation-based data. [ citation needed ]


The user can review all their patient records (including replaying the audio files) via a user interface, e.g. via a web-portal in the browser or stand-alone software on the electronic device. Other functionalities include sharing records with other users, exporting patient records and integration into  EHR systems .


Computer-aided auscultation aimed at detecting and characterizing heart murmurs is called computer-aided heart auscultation (also known as automatic heart sound analysis).


Auscultation of the heart using a stethoscope is the standard examination method worldwide to screen for heart defects by identifying murmurs. It requires that an examining physician have acute hearing and extensive experience. An accurate diagnosis remains challenging for various reasons including noise, high heart rates, and the ability to distinguish innocent from pathological murmurs.
Properly performed, the auscultatory examination of the heart is commonly regarded as an inexpensive, widely available tool in the detection and management of heart disease. [ 10 ]  The auscultation skills of physicians, however, have been reported to be declining. [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ]
This leads to missed disease diagnoses and/or excessive costs for unnecessary and expensive diagnostic testing. A study suggests that more than one third of previously undiagnosed congenital heart defects in newborns are missed by their 6-week examination. [ 18 ]  More than 60% of referrals to medical specialists for costly echocardiography are due to a misdiagnosis of an innocent murmur. [ 14 ]  CAA of the heart thus has the potential to become a cost-effective screening and diagnostic tool, provided that its underlying algorithms have been clinical tested in stringent, blinded fashions for their ability to detect the difference between normal and abnormal heart sounds.


Heart murmurs  (or cardiac murmurs) are audible noises through a stethoscope, generated by a turbulent flow of blood. Heart murmurs need to be distinguished from  heart sounds  which are primarily generated by the beating heart and the heart valves snapping open and shut.
Generally, heart murmurs are classified as  innocent  (also called physiological or functional) or pathological (abnormal). Innocent murmurs are usually harmless, often caused by physiological conditions outside the heart, and the result of certain benign structural defects. Pathological murmurs are most often associated with heart valve problems but may also be caused by a wide array of structural heart defects.
Various characteristics constitute a qualitative description of heart murmurs, including timing ( systolic murmur  and  diastolic murmur ), shape, location, radiation,  intensity , pitch and quality.
CAA systems typically categorize heart sounds and murmurs as Class I and Class III according to the American Heart Association: [ 19 ]


More sophisticated CAA systems provide additional descriptive murmur information like murmur timing, grading, or the ability to identify the positions of the S1/S2 heart sounds.


The detection of heart murmurs in CAA systems is based on the analysis of digitally recorded heart sounds.
Most approaches use the following four stages:


The most common types of performance measures for CAA systems are based on two approaches: retrospective (non-blinded) studies using existing data and prospective blinded clinical studies on new patients.
In retrospective CAA studies, a classifier is trained with  machine learning  algorithms using existing data. The performance of the classifier is then assessed using the same data. Different approaches are used to do this (e.g.,  k-Fold cross-validation ,  leave-one-out cross-validation ).
The main shortcoming of judging the quality (sensitivity, specificity) of a CAA system based on retrospective performance data alone comes from the risk that the approaches used can overestimate the true performance of a given system. Using the same data for training and validation can itself lead to significant  overfitting  of the validation set, because most classifiers can be designed to analyse known data very well, but might not be general enough to correctly classify unknown data; i.e. the results look much better than they would if tested on new, unseen patients. “The true performance of a selected network (CAA system) should be confirmed by measuring its performance on a third independent set of data called a test set”. [ 20 ]  In summary, the reliability of retrospective, non-blinded studies are usually considered to be much lower than that of prospective clinical studies because they are prone to selection bias and retrospective bias. Published examples include Pretorius et al. [ 21 ]
Prospective clinical studies, on the other hand, are better suited to assess the true performance of a CAA system (provided that the study is blinded and well controlled). In a prospective clinical study to evaluate the performance of a CAA system, the output of the CAA system is compared to the  gold standard  diagnoses. In the case of heart murmurs, a suitable gold standard diagnosis would be auscultation-based expert physician diagnosis, stratified by an  echocardiogram-based  diagnosis. Published examples include Lai et al. [ 1 ]


Computing in Cardiology  (formerly known as  Computers in Cardiology ) is a scientific conference held annually since 1974. It brings together scientists from medicine, bioengineering, and other related fields, focused on the application of computational methods in  cardiology . Papers presented at the conference are published by the  Institute of Electrical and Electronics Engineers . Since 2006, papers at the conference have been published under a  Creative Commons  license. The current president of the board of directors is Rob S. Macleod. [ 1 ]


Since 2000, the conference has hosted the annual Physionet/CinC data challenge. [ 2 ] [ 3 ]


Computing in Cardiology is abstracted and indexed in:


Contrast-enhanced ultrasound  ( CEUS ) is the application of  ultrasound   contrast medium  to traditional  medical sonography . Ultrasound  contrast agents  rely on the different ways in which sound waves are reflected from interfaces between substances. This may be the surface of a small air bubble or a more complex structure. Commercially available contrast media are gas-filled  microbubbles  that are administered intravenously to the  systemic circulation . Microbubbles have a high degree of  echogenicity  (the ability of an object to reflect ultrasound waves). There is a great difference in echogenicity between the gas in the microbubbles and the soft  tissue  surroundings of the body. Thus,  ultrasonic imaging  using microbubble contrast agents enhances the ultrasound  backscatter , (reflection) of the ultrasound waves, to produce a  sonogram  with increased contrast due to the high echogenicity difference. Contrast-enhanced ultrasound can be used to image blood  perfusion  in organs, measure  blood flow  rate in the  heart  and other organs, and for other applications.


Targeting  ligands  that bind to  receptors  characteristic of  intravascular  diseases can be conjugated to  microbubbles , enabling the microbubble complex to accumulate selectively in areas of interest, such as  diseased  or abnormal tissues. This form of molecular imaging, known as targeted contrast-enhanced ultrasound, will only generate a strong ultrasound signal if targeted microbubbles bind in the area of interest. Targeted contrast-enhanced ultrasound may have many applications in both  medical diagnostics  and medical therapeutics. However, the targeted technique has not yet been approved by the FDA for clinical use in the United States.


Contrast-enhanced ultrasound is regarded as safe in adults, comparable to the safety of  MRI contrast agents , and better than  radiocontrast agents  used in  contrast CT scans . The more limited safety data in children suggests that such use is as safe as in the adult population. [ 2 ]


An  echocardiogram  is a study of the  heart  using ultrasound. A bubble echocardiogram is an extension of this that uses simple air bubbles as a contrast medium during this study and often has to be requested specifically.


Although colour Doppler can be used to detect abnormal flows between the chambers of the heart (e.g.,  persistent (patent) foramen ovale ), it has a limited  sensitivity . When specifically looking for a defect such as this, small air bubbles can be used as a contrast medium and injected intravenously, where they travel to the right side of the heart. The test would be positive for an abnormal communication if the bubbles are seen passing into the left side of the heart. (Normally, they would exit the  heart  through the  pulmonary artery  and be stopped by the lungs.) This form of bubble contrast medium is generated on an  ad hoc  basis by the testing clinician by agitating  normal saline  (e.g., by rapidly and repeatedly transferring the saline between two connected syringes) immediately prior to injection. [ citation needed ]


There are a variety of microbubble contrast agents. Microbubbles differ in their shell makeup, gas core makeup, and whether or not they are targeted. [ citation needed ]


Regardless of the shell or gas core composition, microbubble size is fairly uniform. They lie within a range of 1–4 micrometres in diameter. That makes them smaller than  red blood cells , which allows them to flow easily through the circulation as well as the microcirculation.


Targeted microbubbles are under preclinical development. They retain the same general features as untargeted microbubbles, but they are outfitted with ligands that bind specific receptors expressed by cell types of interest, such as inflamed cells or cancer cells. Current microbubbles in development are composed of a lipid monolayer shell with a perfluorocarbon gas core. The lipid shell is also covered with a  polyethylene glycol  (PEG) layer. PEG prevents microbubble aggregation and makes the microbubble more non-reactive. It temporarily "hides" the microbubble from the immune system uptake, increasing the amount of circulation time, and hence, imaging time. [ 11 ]  In addition to the PEG layer, the shell is modified with molecules that allow for the attachment of  ligands  that bind certain  receptors . These ligands are attached to the microbubbles using  carbodiimide ,  maleimide , or biotin-streptavidin coupling. [ 11 ]  Biotin-streptavidin is the most popular coupling strategy because  biotin's  affinity for  streptavidin  is very strong and it is easy to label the ligands with biotin. Currently, these ligands are  monoclonal antibodies  produced from animal cell cultures that bind specifically to receptors and molecules expressed by the target cell type. Since the antibodies are not humanized, they will elicit an immune response when used in human therapy. Humanizing antibodies is an expensive and time-intensive process, so it would be ideal to find an alternative source of ligands, such as synthetically manufactured targeting  peptides  that perform the same function, but without the immune issues. [ citation needed ]


There are two forms of contrast-enhanced ultrasound, untargeted (used in the clinic today) and targeted (under preclinical development). The two methods slightly differ from each other.


Untargeted microbubbles, such as the aforementioned SonoVue, Optison, or Levovist, are injected intravenously into the systemic circulation in a small bolus. The microbubbles will remain in the systemic circulation for a certain period of time. During that time, ultrasound waves are directed on the area of interest. When microbubbles in the blood flow past the imaging window, the microbubbles'  compressible  gas cores  oscillate  in response to the high frequency sonic energy field, as described in the  ultrasound  article. The microbubbles reflect a unique  echo  that stands in stark contrast to the surrounding tissue due to the orders of magnitude mismatch between microbubble and tissue echogenicity. The ultrasound system converts the strong echogenicity into a contrast-enhanced image of the area of interest. In this way, the bloodstream's echo is enhanced, thus allowing the clinician to distinguish  blood  from surrounding tissues. [ citation needed ]


Targeted contrast-enhanced ultrasound works in a similar fashion, with a few alterations. Microbubbles targeted with ligands that bind certain molecular markers that are expressed by the area of imaging interest are still injected systemically in a small bolus. Microbubbles theoretically travel through the circulatory system, eventually finding their respective targets and binding specifically. Ultrasound waves can then be directed on the area of interest. If a sufficient number of microbubbles have bound in the area, their compressible gas cores oscillate in response to the high frequency sonic energy field, as described in the  ultrasound  article. The targeted microbubbles also reflect a unique echo that stands in stark contrast to the surrounding tissue due to the orders of magnitude mismatch between microbubble and tissue echogenicity. The ultrasound system converts the strong echogenicity into a contrast-enhanced image of the area of interest, revealing the location of the bound microbubbles. [ 12 ]  Detection of bound microbubbles may then show that the area of interest is expressing that particular molecular marker, which can be indicative of a certain disease state, or identify particular cells in the area of interest. [ citation needed ]


Untargeted contrast-enhanced ultrasound is currently applied in  echocardiography  and  radiology . Targeted contrast-enhanced ultrasound is being developed for a variety of medical applications.


Untargeted microbubbles like Optison and Levovist are currently used in echocardiography. In addition, SonoVue [ 13 ]  ultrasound contrast agent is used in radiology for lesion characterization.


On top of the strengths mentioned in the  medical sonography  entry, contrast-enhanced ultrasound adds these additional advantages:


In addition to the weaknesses mentioned in the  medical sonography  entry, contrast-enhanced ultrasound has the following disadvantages:


Cor triatriatum  (or  triatrial heart ) [ 1 ]  is a  congenital heart defect  where the left  atrium  (cor triatriatum sinistrum) or right atrium (cor triatriatum dextrum) is subdivided by a thin  membrane , resulting in three atrial chambers (hence the name).


Cor triatriatum represents 0.1% of all  congenital   cardiac malformations  and may be associated with other cardiac defects in as many as 50% of cases. The  membrane  may be complete or may contain one or more  fenestrations  of varying size.


Cor triatriatum sinistrum is more common. [ 2 ]  In this defect, there is typically a proximal chamber that receives the  pulmonic veins  and a distal (true) chamber located more  anteriorly  where it empties into the  mitral valve . The membrane that separates the  atrium  into two parts varies significantly in size and shape. It may appear similar to a diaphragm or be funnel-shaped, band-like, entirely intact (imperforate) or contain one or more openings (fenestrations) ranging from small, restrictive-type to large and widely open.


In the  pediatric  population, this anomaly may be associated with major  congenital  cardiac lesions such as  tetralogy of Fallot ,  double outlet right ventricle ,  coarctation of the aorta , partial  anomalous pulmonary venous connection , persistent left  superior vena cava  with unroofed  coronary sinus ,  ventricular septal defect ,  atrioventricular septal (endocardial cushion) defect , and common  atrioventricular canal . Rarely,  asplenia  or  polysplenia  has been reported in these patients. In the adult, cor triatriatum is frequently an isolated finding.


Cor triatriatum dextrum is extremely rare and results from the complete persistence of the right  sinus valve  of the  embryonic heart . The membrane divides the right atrium into a proximal (upper) and a distal (lower) chamber. The upper chamber receives the  venous blood  from both  vena cavae  and the lower chamber is in contact with the  tricuspid valve  and the right  atrial appendage .


The natural history of this defect depends on the size of the communicating orifice between the upper and lower atrial chambers. If the communicating orifice is small, the patient is critically ill and may succumb at a young age (usually during infancy) to congestive  heart failure  and  pulmonary edema . [ 3 ]  If the connection is larger, patients may present in childhood or young adulthood with a clinical picture similar to that of  mitral stenosis . As the malformed membrane calcifies with age, thus further narrowing such opening, decreased  cardiac output  produces features of pulmonary venous  hypertension  and right heart failure—including symptoms of  dyspnea  and  orthopnea , easy  fatigability ,  palpitations  and  shortness of breath , among others. [ 3 ]  Cor triatriatum may also be an incidental finding when it is nonobstructive.


Primarily diagnosed with imaging, such as  echocardiogram  (ultrasound of the heart),  CT , and/or  MRI . [ 3 ]


Treatment of Cor triatriatum varies among cases and is dependent upon presentation of symptoms—incidental finding of the condition in  asymptomatic  patients does not typically require immediate medical management, but for those exhibiting  dyspnea  and  pulmonary congestion , surgical intervention is required. The disorder can be treated surgically by removing the membrane dividing the atrium. The  surgery , which usually occurs by first excising the diaphragm and then closing the  atrial septum , has a reported survival of 90% at five years, with almost all patients becoming  asymptomatic  post-surgery.


A  coronary care unit  ( CCU ) or  cardiac intensive care unit  ( CICU ) is a hospital ward specialized in the care of  patients  with  heart attacks ,  unstable angina ,  cardiac dysrhythmia  and (in practice) various other cardiac conditions that require continuous monitoring and treatment.


The main feature of coronary care is the availability of  telemetry  or the continuous monitoring of the cardiac rhythm by  electrocardiography . This allows early intervention with  medication ,  cardioversion  or  defibrillation , improving the prognosis. As  arrhythmias  are relatively common in this group, patients with myocardial infarction or unstable angina are routinely admitted to the coronary care unit. For other indications, such as  atrial fibrillation , a specific indication is generally necessary, while for others, such as  heart block , coronary care unit admission is standard. [ citation needed ]


In the United States, cardiac conditions accounted for eight of the eighteen conditions and procedures with high ICU utilization (ICU utilization in more than 40% of stays) in 2011. [ 1 ]


In the United States, coronary care units are usually subsets of  intensive care units  (ICU) dedicated to the care of critically ill cardiac patients. These units are usually present in hospitals that routinely engage in cardiothoracic surgery. Invasive monitoring such as with  pulmonary artery catheters  is common, as are supportive modalities such as  mechanical ventilation  and  intra-aortic balloon pumps  (IABP).


Certain hospitals, such as Johns Hopkins  [1] , maintain mixed units consisting of both acute care units for the critically ill, and intermediate care units for patients who are not critical.


Acute coronary care units (ACCUs), also called "critical coronary care units" (CCCUs), are equivalent to intensive care in the level of service provided. Patients with acute myocardial infarction,  cardiogenic shock , or post-operative "open-heart" patients commonly abide here.