Samuel A. Levine and the history of grading systolic murmurs.

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.

William Osler, Maude Abbott, Paul Dudley White, and Helen Taussig: the origins of congenital heart disease in North America.

In 1965, Helen Taussig traced the evolution of knowledge of congenital heart disease (CHD) during the 20th century, beginning with the William Osler-Maude Abbott lineage at McGill University in Montreal, Canada. Osler encouraged Abbott in her CHD pathologic observations. Abbott's London Exhibit (1934) preceded her classic text Atlas of Congenital Cardiac Disease (1936). Taussig's friendship with Abbott (1935) began in Boston; Abbott brought Taussig to meet Paul Dudley White whose text Heart Disease (1931) featured Abbott's work. Taussig visited Abbott (Montreal 1938). Abbott's statistical approach was based on post-mortem malformations; Taussig's concern was why CHD babies died. Abbott (1927) suggested surgery for a patent ductus arteriosus; Taussig conceived of creating a patent ductus arteriosus shunt to improve lung blood flow in cyanotic "blue babies". Surgeon Alfred Blalock and Taussig collaborated with the blue baby shunt operations (1944-1945), opening the field of cardiac surgery in cyanotic babies. Taussig's Congenital Malformations of the Heart text came 2 years later. Sequential contributions by Osler, Abbott, White, and Taussig were landmarks in the evolution of knowledge of CHD in North America.

Mid-myocardial fibrosis by cardiac magnetic resonance in patients with lamin A/C cardiomyopathy: possible substrate for diastolic dysfunction.

AIMS: We sought to identify patterns of myocardial fibrosis in vivo in patients with lamin cardiomyopathy, and to determine its functional significance. METHODS AND RESULTS: Eleven patients sharing the identical mutation in LMNA without contraindication to magnetic resonance were identified from a 1016-member pedigree. Eight autopsy hearts from deceased relatives were reviewed. Patients and age-matched controls underwent cardiac magnetic resonance that included measures of cardiac function and late gadolinium enhancement (LGE). LGE-CMR identified midmyocardial fibrosis of the basal interventricular septum in 5 of 11 LMNA patients that was identical to that seen in 6 autopsy specimens of related genotype-positive family members; this was not present in any of 11 controls. LGE-CMR was positive in the 5 oldest patients in the cohort, age 46 +/- 6 years compared to 24 +/- 10 years for LGE-negative subjects (p = 0.003). Systolic function was abnormal in 2 subjects, both with myocardial fibrosis. LGE-positivity distinguished patients with diastolic dysfunction by mitral inflow velocities from those with normal diastolic function; these patients also had significant left atrial enlargement compared to controls (p < 0.05). CONCLUSIONS: LGE-CMR can identify myocardial fibrosis under genetic control in vivo in patients with heritable cardiomyopathy similar in distribution to that observed at autopsy. Mid-myocardial fibrosis may form the substrate for diastolic dysfunction in these patients.

Association between glycosylated hemoglobin, left ventricular mass and aortic function in nondiabetic individuals with insulin resistance.

OBJECTIVE: An association between glycosylated hemoglobin (GHb) and cardiovascular mortality in nondiabetic individuals has recently been reported. Prompt detection of nondiabetic individuals with high-normal GHb and early cardiovascular involvement may be of value for preventive strategies. In this investigation, a possible relationship between GHb, aortic function and left ventricular (LV) mass in nondiabetic individuals has been studied. METHODS: A total of 263 nondiabetic African-Americans, aged 22-63 (mean 42 +/- 8) years were studied. All individuals were first degree relatives of diabetic patients, had normal oral glucose tolerance test (2-h OGTT) and decreased peripheral action of insulin. LV diameters and mass (echocardiography); ascending and abdominal aortic distensibility (echocardiography, arterial pressure); pulse wave velocity (PWV; electrocardiography, Doppler); fasting glucose; GHb; insulin sensitivity index (S(I)) and 2-h OGTT were measured. Multiple linear and logistic regression analyses were used to identify significant independent associations of fasting glucose; GHb; S(I) and 2-h OGTT with aortic function and LV mass. RESULTS: In fully adjusted multivariate logistic regression analysis, GHb predicted lower values of aortic distensibility (odds ratio (OR) 1.67 95% CI (1.04-2.75), P=0.04); higher PWV (OR 1.79 95% CI (1.09-2.93), P=0.022); and higher values of LV mass (OR 1.56 95% CI (1.08-2.88), P=0.029). Fasting glucose, S(I), and 2 h OGTT were not associated with aortic function and LV mass. CONCLUSION: Higher GHb concentrations, even within 'normal' range, are independently associated with stiffer aorta and increased LV mass and thus may detect nondiabetic individuals at increased cardiovascular risk.

'Tell Brother Regius...' Clifford Allbutt's correspondence with Archibald Malloch during Osler's final illness.

A very close friendship developed between Sir Clifford Allbutt (1836-1925) and Sir William Osler (1849-1919) after they became regius professors at the universities of Cambridge and Oxford, respectively. In 1919, Osler contracted influenza during the 1918-19 pandemic. The disease developed into serious pneumonia and empyema and was the cause of his death. One of his attending physicians in his final illness was Dr T Archibald Malloch (1887-1953) with whom Allbutt began to correspond. Allbutt's letters to Malloch are presented here. Allbutt was an exemplary physician. His handwriting, however, left much to be desired. Transcription of these letters was no mean feat.

Osler, cardiac disease, and students of medicine--Columbus, OH: December 1899.

"Our Distinguished Visitor" was the headline describing the day William Osler honored the Ohio Medical University (OMU) with a visit and clinical lecture. OMU, founded in 1892 and located in downtown Columbus, was the fourth in a series of 5 19th-century Columbus medical schools that were predecessors to The Ohio State University College of Medicine established in 1914. OMU occupied a new 5-story building adjacent to the Protestant Hospital established in 1891. Osler was the guest of Dr Edwin Frazer Wilson, Professor of Therapeutics and Clinical Medicine at OMU, a student of Osler's at the University of Pennsylvania, and an 1885 graduate of that institution. Osler was in Columbus for consultation with one of Dr Wilson's patients. While Osler was in Columbus, a teaching clinic and lecture was arranged at OMU. Murray B. McGonigle, OMU Class of 1900, reported the visit in The Phagocyte, the OMU student publication, and in the Columbus Medical Journal. There was an assemblage of hundreds of students in the amphitheater at clinic hour when OMU Chancellor, Dr David N. Kinsman, introduced Osler. The patient, a 16-year-old young man, was brought to the amphitheater with a history of kidney trouble. Osler's clinical evaluation, physical examination, diagnosis, and discussion of prognosis and treatment provided an object lesson that was impressed on the minds of the students. Following the clinic, Osler addressed the students in his familiar style, demonstrating his easy rapport with students. His comments to the students are classic statements combining personal encouragement with professional attitudes. McGonigle concluded, "these remarks by so eminent an authority are certainly encouraging for the future of the medical student if he will but heed the excellent advice."

Mitral valvular regurgitation : etiology, pathophysiologic mechanisms, clinical manifestations.

The etiology of mitral valvular regurgitation (MVR) has changed in the last 40-50 years in the industrialized countries. A significant reduction in the incidence of rheumatic fever and its sequelae, increase in life expectancy, recognition of new causes of MVR, and advancement in technology are responsible for the metamorphosis of the etiology of MVR. It should be mentioned that MVR still constitutes a major health problem which will increase with the aging population. Recent advances in imaging techniques and hemodynamic studies allow clinicians to better define valvular structure and the pathophysiologic mechanisms of valvular heart disease in clinic practice. When combined with careful clinical history taking and thoughtful clinical examination, the correlation of laboratory studies with the clinical picture should permit definition of the etiology of valvular heart disease in the majority of the patients.

William Osler: slow pulse, stokes-adams disease, and sudden death in families.

In 1903, William Osler, then at Johns Hopkins University, published "On the So-Called Stokes-Adams Disease (Slow Pulse with Syncopal Attacks, etc.)" in The Lancet, classifying a syndrome in evolution. There are thinly disguised references to a brother and to himself in the article, suggesting that Osler was concerned about a family and personal predisposition. Osler's decision to move to Oxford was triggered in part by his personal concerns about cardiac disease. Then, in 1909, Osler contributed a chapter on Stokes-Adams disease to Allbutt and Rolleston's A System of Medicine, complemented by a brilliant pathologic section by the renowned anatomist-morphologist, Arthur Keith. Osler's original contributions involved his emphasis on the importance of family history, his careful clinical and natural history observations, and his recognition of the familial occurrence of bradycardia, Stokes-Adams disease, sudden death, and cardiomyopathy.

Florence Rena Sabin (1871-1953), William Osler (1849-1919) and tuberculosis.

Florence Rena Sabin received her MD from the Johns Hopkins University in 1900. She was one of the first women to become a medical intern at Johns Hopkins and worked for the year of her internship (1900-01) under William Osler. At Johns Hopkins from 1902 to 1925, Sabin studied embryology and histology with mentor Franklin Mall. She became the first woman professor of histology at an American school. Recruited to the Rockefeller Institute (1925), she focused on tuberculosis immunology, tubercle-bacillus biochemistry and haematology. She was the first woman department head at the Rockefeller and, in 1925, the first woman elected to the National Academy of Sciences. Settling in Colorado in 1938, she entered public health, emphasizing tuberculosis control. She received the Trudeau Award in 1945 and the Lasker Award in 1951. Her experience with tuberculosis under Osler's tutelage defined the shape of her work in basic tuberculosis research and in public health.

Volumetric cine CMR to quantify atrial structure and function in patients with atrial dysrhythmias.

PURPOSE: To implement a cardiac magnetic resonance (CMR)-based protocol to define atrial structure and function in individuals with paroxysmal atrial fibrillation (PAF), heritable cardiac conduction and myocardial disease with atrial dysrhtyhmias (HCCMD), and healthy controls. METHODS: Fifteen controls, 20 PAF, and 12 HCCMD subjects underwent CMR examination including: multislice short-axis cine, multislice horizontal long-axis cine, and gadolinium-enhanced coronal plane magnetic resonance angiography (MRA) for pulmonary vein analysis. We also assessed for ventricular myopathy with delayed myocardial enhancement (DME) acquisitions. RESULTS: Right and left ventricular measurements did not differ among the three groups. Seven heritable atrial dysrhythmia subjects and no control or PAF subjects demonstrated midmyocardial fibrosis of the basal interventricular septum by DME. Left atrial (LA) volume at the onset of atrial systole and minimal LA volume were significantly higher in PAF subjects compared to controls (p < 0.05 for both), LA percent emptying was significantly lower in PAF subjects (p < 0.01), and RA percent emptying was significantly lower in PAF subjects compared to controls (p < 0.01), though these differences were not significant when controlling for heart rate, age and gender. There was no significant difference in right atrial (RA) volumes among study groups. Atrial volumes and function did not differ significantly between heritable atrial dysrhtyhmia subjects and controls. PAF subjects had greater frequency of a right middle pulmonary vein (RMPV) than controls (6/20 vs. 3/15) that did not reach statistical significance. CONCLUSIONS: CMR can quantify atrial structure and function in patients with PAF compared to controls. This protocol could not detect abnormalities in atrial function in early affected patients with heritable cardiomyopathy and atrial premature beats.

Cardiovascular effects of type 1 diabetes mellitus in children.

Previous studies have shown that type 1 diabetes mellitus (DM) is associated with cardiovascular abnormalities. Early detection and treatment of these abnormalities may help to prevent the natural progression of the disease. The present study was undertaken to define early cardiovascular abnormalities in children with type 1 DM. Simultaneous evaluation of multiple cardiovascular parameters was performed in 14 children with type 1 DM and 14 age-and gender-matched normal subjects. Measurements of carotid artery intima-media thickness (cIMT, echocardiography), carotid and aortic (ascending and abdominal) distensibility (echocardiography, brachial artery blood pressure), aortic pulse wave velocity (carotid to femoral artery, Doppler), and left ventricular dimensions, mass, and function (echocardiography) were performed. Diabetic children demonstrated a greater cIMT (0.36 +/- 0.04 mm vs 0.31 +/- 0.03 mm, p = 0.002) and decreased carotid artery distensibility (4.4 +/- 1.6 cm(2) . dynes(-1) . 10(-6) vs 6.0 +/- 1.9 cm(2) . dynes(-1) .10(-6), p < 0.01) compared to control. Aortic pulse wave velocity was increased in DM (6.70 +/- 0.39 vs 6.30 +/- 0.31, p = 0.02) compared to control. Left ventricular diameters, mass, and systolic and diastolic function did not differ between the 2 groups. Simultaneous assessment of multiple cardiovascular parameters in children with type 1 DM revealed impaired carotid artery structure and function, and decreased elastic properties of the aorta, before demonstrable changes in left ventricular structure and function could be detected.

The military heart hospitals.

This is the first in a series of four papers that Dr. Wooley wrote exclusively for The American Heart Hospital Journal based on his book, The Irritable Heart of Soldiers and the Origins of Anglo-American Cardiology, published by Ashgate Publishing in 2002.1 Dr. Wooley's book also casts light on the origins of the specialty heart hospital.

The Royal Victoria Hospital at Netley, England.

This is the second in a series of five papers that Dr. Wooley wrote exclusively for The American Heart Hospital Journal based on his book, The Irritable Heart of Soldiers and the Origins of Anglo-American Cardiology, published by Ashgate Publishing in 2002.1 Dr. Wooley's book also casts light on the origins of the specialty heart hospital.

Factors determining left atrial kinetic energy in patients with chronic mitral valve disease.

BACKGROUND: Increased left atrial (LA) work is a major contributor to LA fatigue, LA failure and atrial fibrillation in patients with mitral stenosis (MS) and mitral valvular regurgitation (MVR). The present study was undertaken to define factors that determine LA work in patients with chronic mitral valve disease. PATIENTS AND METHODS: Peak left atrial kinetic energy (LAKE)was used as an index of LA work in 14 patients with MS, 14 with MVR, and 19 normal subjects matched for age and gender with MS and MVR patients. LA stroke volume and ejection fraction were measured from the biplane area-length method using echo techniques. Peak LAKE was obtained from the formula 1/2 mv2, where m = LA stroke volume x 1.06 (blood's specific gravity) and v = transmitral Doppler A-wave velocity. RESULTS: Stepwise regression analysis often clinical and echocardiographic parameters demonstrated that in MS, mitral valve area (r2 = 0.43) and LA maximal volume (r2 = 0.62), in MVR, only LA maximal volume (r2 = 0.42) contributed independently to LAKE. LAKE was greater in MS and MVR compared to control subjects while LA ejection fraction was similar in all groups. CONCLUSIONS: It is concluded that LA work is markedly increased in patients with chronic mitral valve disease. Increased LA work in chronic mitral valve disease may contribute to LA fatigue, LA failure, and atrial fibrillation.

Long-term cardiovascular effects of insulin sensitizer troglitazone on non-diabetic individuals with insulin resistance: double blind, prospective randomized study.

OBJECTIVES: The study was undertaken to assess the long-term cardiovascular effects of troglitazone on non-diabetic individuals with insulin resistance. BACKGROUND: It has been suggested that treatment with troglitazone or similar insulin-sensitizing agents may prevent cardiovascular complications in non-diabetic individuals with insulin resistance. However, the long-term cardiovascular effects of these agents on non-diabetic individuals remain to be defined. METHODS: A total of 137 African-American offspring of type 2 diabetic parents, with normal glucose tolerance and insulin resistance, were randomly divided to receive troglitazone 200 mg/day (n = 40), or placebo (n = 97) for 24 months. Brachial artery blood pressure (sphygmomanometry); aortic pulse wave velocity (carotid to femoral artery, Doppler), left ventricular diameters and mass (echocardiography); ascending and abdominal aortic distensibility (echocardiography, blood pressure); and metabolic and lipid profile were assessed at baseline, 12, and 24 months after randomization (delta 12, delta 24 respectively). RESULTS: The pulse wave velocity increased significantly in the troglitazone group compared to placebo group (p < 0.05). Changes from baseline in the troglitazone group were significant (delta 12 = 1.09 +/- 0.36 m/sec, delta 24 = 2.08 +/- 0.45 m/sec, ANOVA p < 0.001), while pulse wave velocity remained unchanged in the placebo group. This increase in pulse wave velocity is consistent with a decrease in the elastic properties of the aorta. CONCLUSIONS: Long-term administration of troglitazone to non-diabetic African-Americans with insulin resistance was associated with a decrease in the elastic properties of the aorta. Long-term therapy with troglitazone or similar agents for the prevention of cardiovascular complications in non-diabetic individuals with insulin resistance has to be critically evaluated.

William Osler and Jacob Mendez Da Costa: Philadelphia medicine, 1884-1889.

When William Osler (1849-1919), at the age of 35, moved from Montreal to Philadelphia (the leading medical centre in the United States) in 1884, Jacob Mendez Da Costa (1833-1900) was 51, and Chair of Practice at Jefferson Medical College. During Osler's five frenetic years in Philadelphia, he and Da Costa shared medical and professional experiences, interactions with friends and colleagues, and participation in the leading medical organizations in the United States. The shared experiences reflect Philadelphia in the 1880s, the traditions, the times and the individuals. Although Da Costa was considered the greatest clinical teacher of his day, his career embodied Quaker Philadelphia and his legacy does not reflect the stature of the clinician and the man. In time, Osler became Sir William Osler, a man for the ages.