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Samuel A. Levine and the History of Grading Systolic Murmurs

2008; Elsevier BV; Volume: 102; Issue: 8 Linguagem: Inglês

10.1016/j.amjcard.2008.06.027

1879-1913

Mark E. Silverman, Charles F. Wooley,

Cardiovascular Function and Risk Factors

Murmurs were described first by Laennec in 1819, after which the significance of a murmur became a matter of debate. By the late 19th century, many physicians regarded systolic murmurs as “organic,” whereas others believed that they were often “functional.” Samuel Levine became a central figure in separating functional from organic systolic murmurs. Freeman and Levine's 1933 study of 1,000 “noncardiac” subjects determined the frequency, cause, and significance of systolic murmurs. Murmurs were rated on a scale of 1 to 6 grades of intensity. Approximately 20% of their patients had grade 1 or 2 systolic murmurs. Hypertension, fever, tachycardia, and anemia were common factors, and the murmurs were considered functional because they would often disappear when these causes were controlled. Of 19 subjects with grade 3 or 4 murmurs, all were determined to have organic heart disease or anemia. Thus, louder systolic murmurs were found to be a significant finding, as were the cause, location, and effects of posture. They concluded that systolic murmurs often have an explanation and that their grade can be useful in the diagnosis and prognosis. They cautioned that a loud systolic murmur did not necessarily indicate a bad prognosis or even serious heart disease. Levine's system of grading a systolic murmur is valuable and persists into the 21st century. Murmurs were described first by Laennec in 1819, after which the significance of a murmur became a matter of debate. By the late 19th century, many physicians regarded systolic murmurs as “organic,” whereas others believed that they were often “functional.” Samuel Levine became a central figure in separating functional from organic systolic murmurs. Freeman and Levine's 1933 study of 1,000 “noncardiac” subjects determined the frequency, cause, and significance of systolic murmurs. Murmurs were rated on a scale of 1 to 6 grades of intensity. Approximately 20% of their patients had grade 1 or 2 systolic murmurs. Hypertension, fever, tachycardia, and anemia were common factors, and the murmurs were considered functional because they would often disappear when these causes were controlled. Of 19 subjects with grade 3 or 4 murmurs, all were determined to have organic heart disease or anemia. Thus, louder systolic murmurs were found to be a significant finding, as were the cause, location, and effects of posture. They concluded that systolic murmurs often have an explanation and that their grade can be useful in the diagnosis and prognosis. They cautioned that a loud systolic murmur did not necessarily indicate a bad prognosis or even serious heart disease. Levine's system of grading a systolic murmur is valuable and persists into the 21st century. Systolic murmurs do occur but are not common in normal individuals. The louder ones are always associated with some form of cardiovascular disease. —Samuel A. Levine1Levine S.A. The systolic murmur: its clinical significance.JAMA. 1933; 101: 436-438Crossref Scopus (26) Google ScholarSystolic murmurs were heard first by R.T.H Laennec, who likened their distinctive qualities to a file, grate, bellows, or saw. He attributed the noise initially to a valvular origin but later thought it was due to a spasm of a cardiac chamber.2Laennec R. De l'Auscultation Médiate. Brosson et Chaudé, Paris, France1819Google Scholar, 3Duffin J. To See With a Better Eye: A Life of RTH Laennec. Princeton University Press, Princeton, NJ1998Google Scholar Their importance soon became a matter of speculation, with initial correlation by autopsy. By the late 19th century, systolic murmurs were perceived as either “organic” and therefore evidence for serious rheumatic heart disease or mostly “functional” and therefore benign.4Mackenzie J. Diseases of the Heart.2nd ed. Oxford University Press, London, United Kingdom1910Google Scholar James Mackenzie, a pioneer of cardiology in London, stressed that symptoms and limitation of activity, not auscultation, should determine their importance. He emphasized heart muscle function while downplaying the role of valvular disease, saying that it would be better to throw the stethoscope away.4Mackenzie J. Diseases of the Heart.2nd ed. Oxford University Press, London, United Kingdom1910Google Scholar Likewise, the influential Richard Cabot in Boston stated that “systolic murmurs without other signs of cardiac disease are of no importance as evidence of valve lesions.”5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar The loudness of a systolic murmur was not considered as a factor in estimating the underlying process.World War I, Systolic Murmurs, and Neurocirculatory AstheniaThe screening examinations of 4 million American military recruits during World War I added urgent importance to the dilemma, because cardiac murmurs were detected with unexpected frequency, often in association with neurocirculatory asthenia—the so-called soldier's heart—with its disabling symptoms of left chest pain, forceful palpitations, and shortness of breath.6Wooley C.F. The Irritable Heart of Soldiers and the Origins of Anglo-American Cardiology: The US Civil War (1861) to World War I (1918). Ashgate, Burlington, Vermont2002Google Scholar The military decided to train selected physicians to be cardiac examiners, 1 of the earliest steps in the development of “heart men.” As a United States Army medical officer and an astute observer who kept meticulous records, Samuel A. Levine became a central figure in classifying cardiac disorders, and his system of grading a systolic murmur is still widely used today7Wooley C.F. Stang J.M. Samuel A. Levine and his World War I experience.Am J Cardiol. 1988; 62: 952-956Abstract Full Text PDF PubMed Scopus (3) Google Scholar, 8Wooley C.F. Proc, Dr. Sam, Uncle Henry, and the “little green book.”.Am Heart Hosp J. 2005; 3: 8-13Crossref PubMed Google Scholar (Figure 1).Freeman and Levine's Study of the Intensity of Systolic MurmursLevine addressed the clinical significance of the systolic murmur in 2 publications in 1933.1Levine S.A. The systolic murmur: its clinical significance.JAMA. 1933; 101: 436-438Crossref Scopus (26) Google Scholar, 5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar His purpose was “to indicate how its presence should be regarded from a clinical point of view, when it should be considered important, and when it may be viewed lightly.” First, he defined the systolic murmur as “a bruit that has an appreciable duration … between the first and second heart sounds,” making the case that many physicians misuse the term for just a prolongation of the first heart sound. When it came to intensity, Levine stated that “for some years I have expressed the intensity of the systolic murmur in 6 gradations.” In this context, he mentioned albumin testing of the urine and other conditions as examples in which grading could be correlated with the severity of the problem, and he indicated that a scale could be easily applied to systolic murmurs. His report “The Clinical Significance of the Systolic Murmur”5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar was published with A.R. Freeman the same year. This study determined the frequency, cause, and significance of systolic murmurs on the basis of their auscultation of 1,000 consecutive “noncardiac” subjects whose average age was <40 years.5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar The group included 70 infants, 47 medical students, 120 nurses, 100 patients with tuberculosis, and many surgical admissions while mostly avoiding the general medical clinic and wards, with its high concentration of heart patients. Their screening method consisted of defining the length and grading the intensity of the systolic murmur from grade 1 (the faintest definite murmur of some duration after the first heart sound but heard only after several seconds of close listening) to grade 6 (so loud it could be heard without a stethoscope) (Table 1).Table 1Grading of systolic murmursGrade 1Faint. Heard only after a few seconds have elapsedGrade 2A faint murmur heard immediatelyGrade 3Moderately loud murmurGrade 4Loud murmurGrade 5Very loud murmur. Can be heard if only the edge of the stethoscope is in contact with the skin.Grade 6Loudest possible murmur. The murmur can be heard with the stethoscope just removed from the chest and not touching the skin. Open table in a new tab Approximately 20% of their subjects had grade 1 or 2 (slight) systolic murmurs. Hypertension, fever, increased heart rate, and anemia were common associated factors, and the murmurs were considered functional because they would often disappear when these causes were controlled. Of 19 subjects with grade 3 or 4 murmurs, all were determined to have organic heart disease or, rarely, anemia. Thus, louder systolic murmurs were considered a significant finding, as were the cause, location (loud or louder at the apical region than the base of the heart), and effects of posture (louder recumbent as opposed to upright). A systolic murmur appearing only after running was believed to be normal. They concluded from this large experience that systolic murmurs often have an explanation and that their grades could be useful in the diagnosis and prognosis of the condition. They cautioned that a loud systolic murmur did not necessarily indicate a bad prognosis or even serious heart disease. They concluded that “a systolic murmur of greater than grade 1 intensity should be regarded with suspicion and that a proper interpretation of systolic murmurs will lead to more intelligent diagnosis, prognosis, and treatment of disease.”5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar“The Little Green Book” by Samuel Levine and Proctor HarveyBy the 1940s, phonocardiography provided clinicians with an objective method for recording and timing heart sounds and murmurs and brought a new scientific respect to auscultation. The premier book for teaching the art of auscultation on the basis of phonocardiography was Clinical Auscultation of the Heart, published initially by Levine and W. Proctor Harvey8Wooley C.F. Proc, Dr. Sam, Uncle Henry, and the “little green book.”.Am Heart Hosp J. 2005; 3: 8-13Crossref PubMed Google Scholar in 1949 and known affectionately as “the little green book.” Harvey had been an intern at Peter Bent Brigham Hospital whose training was interrupted by World War II. In 1946, he returned to Boston to become Dr. Levine's first cardiac fellow, the start of a long and close relationship (Figure 2). Harvey would record phonocardiograms during the week that the 2 men would review each Saturday afternoon for eventual inclusion in their classic book, which greatly influenced the training of cardiologists and internists after 1949.9Levine S.A. Harvey W.P. Clinical Auscultation of the Heart. W.B. Saunders, Philadelphia, Pennsylvania1949Google Scholar Later, Harvey would become chief of cardiology at Georgetown University and famous worldwide for his innovative methods of teaching auscultation.Figure 2W. Proctor Harvey. From the personal collection of Mark Silverman.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Application of the Grading of Intensity of Systolic MurmursLevine's well-known system of grading systolic murmurs has passed down from 1 generation to the next through textbooks and teaching and has also been used by the insurance industry.10Brackenridge R.D.C. Croxson R.S. Mackenzie R. Brackenridge's Medical Selection of Life Risks.in: 5th ed. Palgrave Macmillan, New York2006: 438-439Google Scholar A strong association has been found between severe aortic stenosis and a grade ≥3 systolic murmur (with a normal ventricle).11Munt B. Legget M.E. Kraft C. Miyake-Hull C. Fujioka M. Otto C. Physical examination in valvular aortic stenosis: correlation with stenosis severity and prediction of clinical outcome.Am Heart J. 1999; 137: 298-306Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Similarly, a grade ≥4 systolic murmur is seen with severe mitral regurgitation, especially with a flail mitral leaflet. When the mitral regurgitation is due to ischemia or a cardiomyopathy, the intensity may not correlate.12Desjardins V.A. Sarano M.E. Tajik A.J. Bailey K.R. Seward J.B. Intensity of murmurs correlates with severity of valvular regurgitation.Am J Med. 1996; 100: 149-156Abstract Full Text PDF PubMed Scopus (84) Google Scholar The systolic murmur is known to become louder and longer with increasingly severe pulmonary stenosis and a larger atrial septal defect.13Perloff J.K. The Clinical Recognition of Congenital Heart Disease. W.B. Saunders, Philadelphia, Pennsylvania1994Google Scholar, 14Alpert J.S. Dalen J.E. Valvular Heart Disease.2nd ed. Little, Brown, Boston, Massachusetts1987Google Scholar An inspiratory increase in the intensity of a systolic murmur over the xyphoid area identifies the presence of tricuspid regurgitation (Carvallo's sign).15Rivero-Carvallo J.M. Signo para el diagnositico de las insuficiencias tricuspideas.Arch Inst Card Mex. 1946; 16: 531PubMed Google Scholar Paradoxically, a loud systolic murmur is usual with a small ventricular septal defect, the well-known “Roger murmur.”Levine's system is often misused. For example, a soft murmur heard immediately is often labeled grade 1 instead of grade 2, as specified in the Levine classification. Furthermore, a grade 4 murmur on the Levine grading scale does not require the presence of a thrill, as is commonly taught.Samuel A. LevineLevine was born in Lomza, Poland, in 1891. He was brought to the United States when he was 3 years old. Educated in Boston, Levine had his medical training at Harvard Medical School and graduated in 1914. He was an intern to Henry Christian at Peter Bent Brigham Hospital, joining the medical staff in 1915.16Wooley C.F. Stang J.M. Samuel A. Levine's First World War encounters with Mackenzie and Lewis.Br Heart J. 1990; 64: 166-170Crossref PubMed Scopus (2) Google Scholar He was scheduled to study under Thomas Lewis in London, but the outbreak of World War I interrupted his plans. Instead, Levine went to the Rockefeller Institute, where he collaborated with Alfred E. Cohn. Later, when the United States entered the war in 1917, Levine was 1 of a small group of American medical officers who worked with Thomas Lewis at the Military Heart Hospital in Colchester, England, where he was fortunate to interact with William Osler, James Mackenzie, and Clifford Allbutt8Wooley C.F. Proc, Dr. Sam, Uncle Henry, and the “little green book.”.Am Heart Hosp J. 2005; 3: 8-13Crossref PubMed Google Scholar (Figure 3). After the war, Levine returned to Boston and a future illustrious career in developing the new field of cardiovascular medicine. Among his 250 publications, his reports on myocardial infarction presenting as an acute abdomen (1918), pernicious anemia and gastric anacidity (1921), the first successful mitral valvulotomy (1923), and the clinical features of coronary thrombosis (1929) were landmarks. His 1951 recommendation that patients with infarctions be allowed up in the armchair greatly shortened hospital stays after infarction. As an astute bedside observer, entertaining teacher, and prolific author, he had few peers.17Levine H.J. Samuel A. Levine (1891–1966).Clin Cardiol. 1992; 15: 473-476Crossref PubMed Scopus (1) Google Scholar His credo was “the first purpose in teaching is that the practicing physician should acquire that information which is directly helpful in the care of the patient.”Figure 3Samuel A. Levine during a visit to The Ohio State University, 1960. Reproduced with permission from Br Heart J.16Wooley C.F. Stang J.M. Samuel A. Levine's First World War encounters with Mackenzie and Lewis.Br Heart J. 1990; 64: 166-170Crossref PubMed Scopus (2) Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT)When Dr. Levine died in 1966, Evan Bedford, a noted English cardiologist, recalled Levine's Anglo-American experiences. He described him as a “true anglophile” and an enthusiastic and successful teacher with a flair for being in the vanguard of many advances in cardiology.18Bedford D.E. Obituary Samuel Albert Levine (1891–1966).Br Heart J. 1966; 28: 853-854Crossref PubMed Google ScholarIn conclusion, although the origin of Levine's grading system of systolic cardiac murmurs has been obscured by the mists of time, his grading system of systolic murmurs is valuable and persists into the 21st century. Systolic murmurs do occur but are not common in normal individuals. The louder ones are always associated with some form of cardiovascular disease. —Samuel A. Levine1Levine S.A. The systolic murmur: its clinical significance.JAMA. 1933; 101: 436-438Crossref Scopus (26) Google Scholar Systolic murmurs were heard first by R.T.H Laennec, who likened their distinctive qualities to a file, grate, bellows, or saw. He attributed the noise initially to a valvular origin but later thought it was due to a spasm of a cardiac chamber.2Laennec R. De l'Auscultation Médiate. Brosson et Chaudé, Paris, France1819Google Scholar, 3Duffin J. To See With a Better Eye: A Life of RTH Laennec. Princeton University Press, Princeton, NJ1998Google Scholar Their importance soon became a matter of speculation, with initial correlation by autopsy. By the late 19th century, systolic murmurs were perceived as either “organic” and therefore evidence for serious rheumatic heart disease or mostly “functional” and therefore benign.4Mackenzie J. Diseases of the Heart.2nd ed. Oxford University Press, London, United Kingdom1910Google Scholar James Mackenzie, a pioneer of cardiology in London, stressed that symptoms and limitation of activity, not auscultation, should determine their importance. He emphasized heart muscle function while downplaying the role of valvular disease, saying that it would be better to throw the stethoscope away.4Mackenzie J. Diseases of the Heart.2nd ed. Oxford University Press, London, United Kingdom1910Google Scholar Likewise, the influential Richard Cabot in Boston stated that “systolic murmurs without other signs of cardiac disease are of no importance as evidence of valve lesions.”5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar The loudness of a systolic murmur was not considered as a factor in estimating the underlying process. World War I, Systolic Murmurs, and Neurocirculatory AstheniaThe screening examinations of 4 million American military recruits during World War I added urgent importance to the dilemma, because cardiac murmurs were detected with unexpected frequency, often in association with neurocirculatory asthenia—the so-called soldier's heart—with its disabling symptoms of left chest pain, forceful palpitations, and shortness of breath.6Wooley C.F. The Irritable Heart of Soldiers and the Origins of Anglo-American Cardiology: The US Civil War (1861) to World War I (1918). Ashgate, Burlington, Vermont2002Google Scholar The military decided to train selected physicians to be cardiac examiners, 1 of the earliest steps in the development of “heart men.” As a United States Army medical officer and an astute observer who kept meticulous records, Samuel A. Levine became a central figure in classifying cardiac disorders, and his system of grading a systolic murmur is still widely used today7Wooley C.F. Stang J.M. Samuel A. Levine and his World War I experience.Am J Cardiol. 1988; 62: 952-956Abstract Full Text PDF PubMed Scopus (3) Google Scholar, 8Wooley C.F. Proc, Dr. Sam, Uncle Henry, and the “little green book.”.Am Heart Hosp J. 2005; 3: 8-13Crossref PubMed Google Scholar (Figure 1). The screening examinations of 4 million American military recruits during World War I added urgent importance to the dilemma, because cardiac murmurs were detected with unexpected frequency, often in association with neurocirculatory asthenia—the so-called soldier's heart—with its disabling symptoms of left chest pain, forceful palpitations, and shortness of breath.6Wooley C.F. The Irritable Heart of Soldiers and the Origins of Anglo-American Cardiology: The US Civil War (1861) to World War I (1918). Ashgate, Burlington, Vermont2002Google Scholar The military decided to train selected physicians to be cardiac examiners, 1 of the earliest steps in the development of “heart men.” As a United States Army medical officer and an astute observer who kept meticulous records, Samuel A. Levine became a central figure in classifying cardiac disorders, and his system of grading a systolic murmur is still widely used today7Wooley C.F. Stang J.M. Samuel A. Levine and his World War I experience.Am J Cardiol. 1988; 62: 952-956Abstract Full Text PDF PubMed Scopus (3) Google Scholar, 8Wooley C.F. Proc, Dr. Sam, Uncle Henry, and the “little green book.”.Am Heart Hosp J. 2005; 3: 8-13Crossref PubMed Google Scholar (Figure 1). Freeman and Levine's Study of the Intensity of Systolic MurmursLevine addressed the clinical significance of the systolic murmur in 2 publications in 1933.1Levine S.A. The systolic murmur: its clinical significance.JAMA. 1933; 101: 436-438Crossref Scopus (26) Google Scholar, 5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar His purpose was “to indicate how its presence should be regarded from a clinical point of view, when it should be considered important, and when it may be viewed lightly.” First, he defined the systolic murmur as “a bruit that has an appreciable duration … between the first and second heart sounds,” making the case that many physicians misuse the term for just a prolongation of the first heart sound. When it came to intensity, Levine stated that “for some years I have expressed the intensity of the systolic murmur in 6 gradations.” In this context, he mentioned albumin testing of the urine and other conditions as examples in which grading could be correlated with the severity of the problem, and he indicated that a scale could be easily applied to systolic murmurs. His report “The Clinical Significance of the Systolic Murmur”5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar was published with A.R. Freeman the same year. This study determined the frequency, cause, and significance of systolic murmurs on the basis of their auscultation of 1,000 consecutive “noncardiac” subjects whose average age was <40 years.5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar The group included 70 infants, 47 medical students, 120 nurses, 100 patients with tuberculosis, and many surgical admissions while mostly avoiding the general medical clinic and wards, with its high concentration of heart patients. Their screening method consisted of defining the length and grading the intensity of the systolic murmur from grade 1 (the faintest definite murmur of some duration after the first heart sound but heard only after several seconds of close listening) to grade 6 (so loud it could be heard without a stethoscope) (Table 1).Table 1Grading of systolic murmursGrade 1Faint. Heard only after a few seconds have elapsedGrade 2A faint murmur heard immediatelyGrade 3Moderately loud murmurGrade 4Loud murmurGrade 5Very loud murmur. Can be heard if only the edge of the stethoscope is in contact with the skin.Grade 6Loudest possible murmur. The murmur can be heard with the stethoscope just removed from the chest and not touching the skin. Open table in a new tab Approximately 20% of their subjects had grade 1 or 2 (slight) systolic murmurs. Hypertension, fever, increased heart rate, and anemia were common associated factors, and the murmurs were considered functional because they would often disappear when these causes were controlled. Of 19 subjects with grade 3 or 4 murmurs, all were determined to have organic heart disease or, rarely, anemia. Thus, louder systolic murmurs were considered a significant finding, as were the cause, location (loud or louder at the apical region than the base of the heart), and effects of posture (louder recumbent as opposed to upright). A systolic murmur appearing only after running was believed to be normal. They concluded from this large experience that systolic murmurs often have an explanation and that their grades could be useful in the diagnosis and prognosis of the condition. They cautioned that a loud systolic murmur did not necessarily indicate a bad prognosis or even serious heart disease. They concluded that “a systolic murmur of greater than grade 1 intensity should be regarded with suspicion and that a proper interpretation of systolic murmurs will lead to more intelligent diagnosis, prognosis, and treatment of disease.”5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar Levine addressed the clinical significance of the systolic murmur in 2 publications in 1933.1Levine S.A. The systolic murmur: its clinical significance.JAMA. 1933; 101: 436-438Crossref Scopus (26) Google Scholar, 5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar His purpose was “to indicate how its presence should be regarded from a clinical point of view, when it should be considered important, and when it may be viewed lightly.” First, he defined the systolic murmur as “a bruit that has an appreciable duration … between the first and second heart sounds,” making the case that many physicians misuse the term for just a prolongation of the first heart sound. When it came to intensity, Levine stated that “for some years I have expressed the intensity of the systolic murmur in 6 gradations.” In this context, he mentioned albumin testing of the urine and other conditions as examples in which grading could be correlated with the severity of the problem, and he indicated that a scale could be easily applied to systolic murmurs. His report “The Clinical Significance of the Systolic Murmur”5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar was published with A.R. Freeman the same year. This study determined the frequency, cause, and significance of systolic murmurs on the basis of their auscultation of 1,000 consecutive “noncardiac” subjects whose average age was <40 years.5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar The group included 70 infants, 47 medical students, 120 nurses, 100 patients with tuberculosis, and many surgical admissions while mostly avoiding the general medical clinic and wards, with its high concentration of heart patients. Their screening method consisted of defining the length and grading the intensity of the systolic murmur from grade 1 (the faintest definite murmur of some duration after the first heart sound but heard only after several seconds of close listening) to grade 6 (so loud it could be heard without a stethoscope) (Table 1). Approximately 20% of their subjects had grade 1 or 2 (slight) systolic murmurs. Hypertension, fever, increased heart rate, and anemia were common associated factors, and the murmurs were considered functional because they would often disappear when these causes were controlled. Of 19 subjects with grade 3 or 4 murmurs, all were determined to have organic heart disease or, rarely, anemia. Thus, louder systolic murmurs were considered a significant finding, as were the cause, location (loud or louder at the apical region than the base of the heart), and effects of posture (louder recumbent as opposed to upright). A systolic murmur appearing only after running was believed to be normal. They concluded from this large experience that systolic murmurs often have an explanation and that their grades could be useful in the diagnosis and prognosis of the condition. They cautioned that a loud systolic murmur did not necessarily indicate a bad prognosis or even serious heart disease. They concluded that “a systolic murmur of greater than grade 1 intensity should be regarded with suspicion and that a proper interpretation of systolic murmurs will lead to more intelligent diagnosis, prognosis, and treatment of disease.”5Freeman A.R. Levine S.A. The clinical significance of the systolic murmur A study of 1000 consecutive “non-cardiac” cases.Ann Intern Med. 1933; 6: 1371-1385Crossref Google Scholar “The Little Green Book” by Samuel Levine and Proctor HarveyBy the 1940s, phonocardiography provided clinicians with an objective method for recording and timing heart sounds and murmurs and brought a new scientific respect to auscultation. The premier book for teaching the art of auscultation on the basis of phonocardiography was Clinical Auscultation of the Heart, published initially by Levine and W. Proctor Harvey8Wooley C.F. Proc, Dr. Sam, Uncle Henry, and the “little green book.”.Am Heart Hosp J. 2005; 3: 8-13Crossref PubMed Google Scholar in 1949 and known affectionately as “the little green book.” Harvey had been an intern at Peter Bent Brigham Hospital whose training was interrupted by World War II. In 1946, he returned to Boston to become Dr. Levine's first cardiac fellow, the start of a long and close relationship (Figure 2). Harvey would record phonocardiograms during the week that the 2 men would review each Saturday afternoon for eventual inclusion in their classic book, which greatly influenced the training of cardiologists and internists after 1949.9Levine S.A. Harvey W.P. Clinical Auscultation of the Heart. W.B. Saunders, Philadelphia, Pennsylvania1949Google Scholar Later, Harvey would become chief of cardiology at Georgetown University and famous worldwide for his innovative methods of teaching auscultation. By the 1940s, phonocardiography provided clinicians with an objective method for recording and timing heart sounds and murmurs and brought a new scientific respect to auscultation. The premier book for teaching the art of auscultation on the basis of phonocardiography was Clinical Auscultation of the Heart, published initially by Levine and W. Proctor Harvey8Wooley C.F. Proc, Dr. Sam, Uncle Henry, and the “little green book.”.Am Heart Hosp J. 2005; 3: 8-13Crossref PubMed Google Scholar in 1949 and known affectionately as “the little green book.” Harvey had been an intern at Peter Bent Brigham Hospital whose training was interrupted by World War II. In 1946, he returned to Boston to become Dr. Levine's first cardiac fellow, the start of a long and close relationship (Figure 2). Harvey would record phonocardiograms during the week that the 2 men would review each Saturday afternoon for eventual inclusion in their classic book, which greatly influenced the training of cardiologists and internists after 1949.9Levine S.A. Harvey W.P. Clinical Auscultation of the Heart. W.B. Saunders, Philadelphia, Pennsylvania1949Google Scholar Later, Harvey would become chief of cardiology at Georgetown University and famous worldwide for his innovative methods of teaching auscultation. Application of the Grading of Intensity of Systolic MurmursLevine's well-known system of grading systolic murmurs has passed down from 1 generation to the next through textbooks and teaching and has also been used by the insurance industry.10Brackenridge R.D.C. Croxson R.S. Mackenzie R. Brackenridge's Medical Selection of Life Risks.in: 5th ed. Palgrave Macmillan, New York2006: 438-439Google Scholar A strong association has been found between severe aortic stenosis and a grade ≥3 systolic murmur (with a normal ventricle).11Munt B. Legget M.E. Kraft C. Miyake-Hull C. Fujioka M. Otto C. Physical examination in valvular aortic stenosis: correlation with stenosis severity and prediction of clinical outcome.Am Heart J. 1999; 137: 298-306Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Similarly, a grade ≥4 systolic murmur is seen with severe mitral regurgitation, especially with a flail mitral leaflet. When the mitral regurgitation is due to ischemia or a cardiomyopathy, the intensity may not correlate.12Desjardins V.A. Sarano M.E. Tajik A.J. Bailey K.R. Seward J.B. Intensity of murmurs correlates with severity of valvular regurgitation.Am J Med. 1996; 100: 149-156Abstract Full Text PDF PubMed Scopus (84) Google Scholar The systolic murmur is known to become louder and longer with increasingly severe pulmonary stenosis and a larger atrial septal defect.13Perloff J.K. The Clinical Recognition of Congenital Heart Disease. W.B. Saunders, Philadelphia, Pennsylvania1994Google Scholar, 14Alpert J.S. Dalen J.E. Valvular Heart Disease.2nd ed. Little, Brown, Boston, Massachusetts1987Google Scholar An inspiratory increase in the intensity of a systolic murmur over the xyphoid area identifies the presence of tricuspid regurgitation (Carvallo's sign).15Rivero-Carvallo J.M. Signo para el diagnositico de las insuficiencias tricuspideas.Arch Inst Card Mex. 1946; 16: 531PubMed Google Scholar Paradoxically, a loud systolic murmur is usual with a small ventricular septal defect, the well-known “Roger murmur.”Levine's system is often misused. For example, a soft murmur heard immediately is often labeled grade 1 instead of grade 2, as specified in the Levine classification. Furthermore, a grade 4 murmur on the Levine grading scale does not require the presence of a thrill, as is commonly taught. Levine's well-known system of grading systolic murmurs has passed down from 1 generation to the next through textbooks and teaching and has also been used by the insurance industry.10Brackenridge R.D.C. Croxson R.S. Mackenzie R. Brackenridge's Medical Selection of Life Risks.in: 5th ed. Palgrave Macmillan, New York2006: 438-439Google Scholar A strong association has been found between severe aortic stenosis and a grade ≥3 systolic murmur (with a normal ventricle).11Munt B. Legget M.E. Kraft C. Miyake-Hull C. Fujioka M. Otto C. Physical examination in valvular aortic stenosis: correlation with stenosis severity and prediction of clinical outcome.Am Heart J. 1999; 137: 298-306Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Similarly, a grade ≥4 systolic murmur is seen with severe mitral regurgitation, especially with a flail mitral leaflet. When the mitral regurgitation is due to ischemia or a cardiomyopathy, the intensity may not correlate.12Desjardins V.A. Sarano M.E. Tajik A.J. Bailey K.R. Seward J.B. Intensity of murmurs correlates with severity of valvular regurgitation.Am J Med. 1996; 100: 149-156Abstract Full Text PDF PubMed Scopus (84) Google Scholar The systolic murmur is known to become louder and longer with increasingly severe pulmonary stenosis and a larger atrial septal defect.13Perloff J.K. The Clinical Recognition of Congenital Heart Disease. W.B. Saunders, Philadelphia, Pennsylvania1994Google Scholar, 14Alpert J.S. Dalen J.E. Valvular Heart Disease.2nd ed. Little, Brown, Boston, Massachusetts1987Google Scholar An inspiratory increase in the intensity of a systolic murmur over the xyphoid area identifies the presence of tricuspid regurgitation (Carvallo's sign).15Rivero-Carvallo J.M. Signo para el diagnositico de las insuficiencias tricuspideas.Arch Inst Card Mex. 1946; 16: 531PubMed Google Scholar Paradoxically, a loud systolic murmur is usual with a small ventricular septal defect, the well-known “Roger murmur.” Levine's system is often misused. For example, a soft murmur heard immediately is often labeled grade 1 instead of grade 2, as specified in the Levine classification. Furthermore, a grade 4 murmur on the Levine grading scale does not require the presence of a thrill, as is commonly taught. Samuel A. LevineLevine was born in Lomza, Poland, in 1891. He was brought to the United States when he was 3 years old. Educated in Boston, Levine had his medical training at Harvard Medical School and graduated in 1914. He was an intern to Henry Christian at Peter Bent Brigham Hospital, joining the medical staff in 1915.16Wooley C.F. Stang J.M. Samuel A. Levine's First World War encounters with Mackenzie and Lewis.Br Heart J. 1990; 64: 166-170Crossref PubMed Scopus (2) Google Scholar He was scheduled to study under Thomas Lewis in London, but the outbreak of World War I interrupted his plans. Instead, Levine went to the Rockefeller Institute, where he collaborated with Alfred E. Cohn. Later, when the United States entered the war in 1917, Levine was 1 of a small group of American medical officers who worked with Thomas Lewis at the Military Heart Hospital in Colchester, England, where he was fortunate to interact with William Osler, James Mackenzie, and Clifford Allbutt8Wooley C.F. Proc, Dr. Sam, Uncle Henry, and the “little green book.”.Am Heart Hosp J. 2005; 3: 8-13Crossref PubMed Google Scholar (Figure 3). After the war, Levine returned to Boston and a future illustrious career in developing the new field of cardiovascular medicine. Among his 250 publications, his reports on myocardial infarction presenting as an acute abdomen (1918), pernicious anemia and gastric anacidity (1921), the first successful mitral valvulotomy (1923), and the clinical features of coronary thrombosis (1929) were landmarks. His 1951 recommendation that patients with infarctions be allowed up in the armchair greatly shortened hospital stays after infarction. As an astute bedside observer, entertaining teacher, and prolific author, he had few peers.17Levine H.J. Samuel A. Levine (1891–1966).Clin Cardiol. 1992; 15: 473-476Crossref PubMed Scopus (1) Google Scholar His credo was “the first purpose in teaching is that the practicing physician should acquire that information which is directly helpful in the care of the patient.”When Dr. Levine died in 1966, Evan Bedford, a noted English cardiologist, recalled Levine's Anglo-American experiences. He described him as a “true anglophile” and an enthusiastic and successful teacher with a flair for being in the vanguard of many advances in cardiology.18Bedford D.E. Obituary Samuel Albert Levine (1891–1966).Br Heart J. 1966; 28: 853-854Crossref PubMed Google ScholarIn conclusion, although the origin of Levine's grading system of systolic cardiac murmurs has been obscured by the mists of time, his grading system of systolic murmurs is valuable and persists into the 21st century. Levine was born in Lomza, Poland, in 1891. He was brought to the United States when he was 3 years old. Educated in Boston, Levine had his medical training at Harvard Medical School and graduated in 1914. He was an intern to Henry Christian at Peter Bent Brigham Hospital, joining the medical staff in 1915.16Wooley C.F. Stang J.M. Samuel A. Levine's First World War encounters with Mackenzie and Lewis.Br Heart J. 1990; 64: 166-170Crossref PubMed Scopus (2) Google Scholar He was scheduled to study under Thomas Lewis in London, but the outbreak of World War I interrupted his plans. Instead, Levine went to the Rockefeller Institute, where he collaborated with Alfred E. Cohn. Later, when the United States entered the war in 1917, Levine was 1 of a small group of American medical officers who worked with Thomas Lewis at the Military Heart Hospital in Colchester, England, where he was fortunate to interact with William Osler, James Mackenzie, and Clifford Allbutt8Wooley C.F. Proc, Dr. Sam, Uncle Henry, and the “little green book.”.Am Heart Hosp J. 2005; 3: 8-13Crossref PubMed Google Scholar (Figure 3). After the war, Levine returned to Boston and a future illustrious career in developing the new field of cardiovascular medicine. Among his 250 publications, his reports on myocardial infarction presenting as an acute abdomen (1918), pernicious anemia and gastric anacidity (1921), the first successful mitral valvulotomy (1923), and the clinical features of coronary thrombosis (1929) were landmarks. His 1951 recommendation that patients with infarctions be allowed up in the armchair greatly shortened hospital stays after infarction. As an astute bedside observer, entertaining teacher, and prolific author, he had few peers.17Levine H.J. Samuel A. Levine (1891–1966).Clin Cardiol. 1992; 15: 473-476Crossref PubMed Scopus (1) Google Scholar His credo was “the first purpose in teaching is that the practicing physician should acquire that information which is directly helpful in the care of the patient.” When Dr. Levine died in 1966, Evan Bedford, a noted English cardiologist, recalled Levine's Anglo-American experiences. He described him as a “true anglophile” and an enthusiastic and successful teacher with a flair for being in the vanguard of many advances in cardiology.18Bedford D.E. Obituary Samuel Albert Levine (1891–1966).Br Heart J. 1966; 28: 853-854Crossref PubMed Google Scholar In conclusion, although the origin of Levine's grading system of systolic cardiac murmurs has been obscured by the mists of time, his grading system of systolic murmurs is valuable and persists into the 21st century. Shortly after this report was completed, my coauthor Charles Wooley died. He was a mentor for me and many others, and I am grateful for the opportunity to have worked closely with him. We appreciate the review and suggestions of Charles B. Upshaw, Jr., MD, Aubrey Leatham, MD, and Joseph K. Perloff, MD, and the secretarial help of Stacie Stepney.