Dr. Lewis A. Conner
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Cardiology evolved as a subspecialty during the early decades of the 20th century. It arose from the introduction of the electrocardiogram into clinical practice and from focused efforts of physiologically oriented academic physicians and public health oriented practitioners to learn more about the nature and effective treatment of heart disease. Dr. Lewis A. Conner, Professor of Medicine and Chairman of the Department of Medicine at Cornell (Figure 1), helped establish outpatient clinics for cardiac patients in the New York area, and presided over the formation in 1915 the Association for the Prevention and Relief of Heart Disease, serving as its first Director. The goals of this association were to discover methods for detection, prevention, and dissemination of knowledge about heart disease, and to organize care for patients with heart disease. Conner, sometimes called "Cornell's Osler" because of his clinical excellence, compassionate care, and emphasis on bedside teaching, was a leading participant at the 1922 meeting during which plans were made to expand this regional heart disease organization to national stature. The new organization was called, at Conner's suggestion, the American Heart Association to emphasize its continental scope. He served as its first President, from 1924 to 1925, and he was the founding editor of the new American Heart Journal.
1927-1940: The electrocardiographic recognition of acute myocardial ischemia and myocardial infarction
For the first twenty years of its clinical availability, electrocardiography was focused on clarification of rhythm disorders. Because recordings were limited to the three standard limb leads introduced by Einthoven, spatial localization of electrical activity in the heart beyond the frontal plane was impossible. This limited anatomical insights into the ECG waveforms, beyond relatively weak correlations of frontal plane axis with "preponderance" (hypertrophy) of the left or the right ventricle. The ability to recognize and to localize ischemia and infarction was severely limited. Dr. Harold E. B. Pardee, an attending physician at the New York Hospital and a faculty member at Cornell, was one of the early electrocardiographers in the United States. He served the newly organized American Heart Association as its first chairman of the Committee for Coordination of Investigation. Pardee's ECG textbook, which went through four editions, was an American standard for decades. He is perhaps best known for his description of ST segment elevation during the acute phase of myocardial infarction, which was published in 1920 in the Archives of Internal Medicine and called "Pardee's sign" by Paul Dudley White.
Dr. Irving Wright
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Heparin was first isolated in the early years of the 20th century, purification and the earliest clinical use in humans began in the mid 1930s, but the first patient to receive heparin in the US was a young man with "malignant recurrent thrombophlebitis" treated by Cornell's Dr. Irving Wright (Figure 2) in 1939. The oral anticoagulant dicumarol was first isolated in 1939, was given to the first human volunteers in 1940, the first oral report was in early 1941, and Irving Wright and his group soon followed with a presentation in late 1941 and a publication in 1942. Dr. Wright was the first to use dicumarol therapeutically, in the same person who was the first US patient to receive heparin 3 years earlier. A preliminary report from Cornell using dicumarol to treat acute MI came in 1946, and what may have been the first large clinical trial, sponsored by the American Heart Association and published in the American Heart Journal with first author Wright as Chairman of the Steering Committee, came in 1948. Wright served as President of the American Heart Association from 1952 to 1953. Perhaps one of the most important strengths of American medicine in general and Cardiology in particular is the randomized clinical trial – and the first large, widely reported such trial was done over half a century ago here at Weill Cornell.
Cornell's Coronary Care Unit circa 1965, with Dr. Thomas Killip right, and nurse at left
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The first coronary care unit ("CCU") was described in the medical literature in the early 1960s, but this simple innovation – concentrating patients with acute myocardial infarction, a potentially lethal disease, in one location with specially trained personnel and instant availability of emergency equipment for defibrillation – was spread throughout the United States and the world as much by work done here at NewYork-Presbyterian Hospital/Weill Cornell Medical Center as anywhere else. Drs. John Kimball, first director of the CCU and Thomas Killip, then Chief of Cardiology, opened one of the earliest units in the US, initially 4 beds with monitors and defibrillators at every bedside (Figure 3). The Medical Board was persuaded to allow nurses to read ECGs, diagnose life-threatening arrhythmias, and administer emergency medications as well as defibrillation – a revolutionary step at the time. Kimball and Killip published in 1967 what was probably the single most influential journal article describing a major improvement in survival in CCUs, and within a few years every hospital in the country had such a unit. Cornell cardiologists trained CCU nurses all over the country in those early years. A description of how sick the patient was, and the likely mortality rate, has survived to this day as the "Killip classification", and Cornell was one of several centers around the country, the "Myocardial Infarction Research Units" ("MIRU") who collectively and competitively pioneered aggressive treatment of acute MI. Before the MIRUs, patients with acute MI were put to bed for 3 weeks or more, were sedated, not allowed to move (to the point where nurses would feed and wash patients), and certainly were never subjected to invasive procedures, nothing beyond a simple intravenous line. Cornell was one of the first centers to put small catheters into the heart itself within 24 hours of an MI, and the MIRU experience led eventually to earlier ambulation, early cardiac catheterization and angioplasty, anti-thrombotic therapy, and a host of modern treatments for acute MI.
1975-1985: The vasoconstrictor-volume understanding of hypertension, elucidation of the renin-angiotensin axis, and the clinical introduction of ACE inhibitors into medicine
The search for a pathophysiologic understanding of hypertension led to recognition of the critical role of the complex renin-angiotensin axis in controlling the vasoconstrictor and volume elements of blood pressure. Work carried out at Cornell after 1975 by Dr. John Laragh and colleagues popularized "renin profiling" in hypertension and clarified the diagnostic and therapeutic importance of distinguishing high renin (vasoconstrictive) from low renin (volume overload) forms of hypertension. While the volume overload type of hypertension was generally treatable with simple diuretics, the vasoconstricor type was found to respond to beta-blockade (to reduce renin production). Profiling of hypertension therefore led to specific therapy targeted to the underlying pathophysiology, while providing prognostic value regarding likelihood of vascular complications. A early specific biochemical inhibitor of the angiotensin converting enzyme (ACE) was found to reduce vasoconstriction by reducing the circulating levels of angiotensin in the blood. The earliest laboratory and clinical work with angiotensin converting enzyme and inhibitors, done here at Weill Cornell, led directly to the introduction of captopril, the prototype "ACE inhibitor." In addition. the "captopril test", developed here, became popular as a means of diagnosing renal artery stenosis, an important occult form of high renin hypertension that could be treated by opening the obstructed artery. Widespread recognition of the role of renin-angiotensin system activation in patients with heart failure soon led to the use of ACE inhibitors for afterload reduction in a variety of clinical disorders.
1989: The cellular and molecular bases for the right ventricular outflow tract tachycardia
Since its initial description in the 1920s, right ventricular outflow tract (RVOT) tachycardia has intrigued physicians. Unlike most ventricular arrhythmias, it occurred in the absence of structural heart disease and appeared to be mechanistically different from other arrhythmias. Beginning in the late 1980s, Dr. Bruce Lerman and his team began to unravel some of the mysteries surrounding this entity. The first important finding was identifying the novel cellular mechanism responsible for this arrhythmia. The arrhythmia was demonstrated to be due to cAMP-mediated triggered activity (the first clinical arrhythmia identified as such), which is characterized by a dependence on catecholamine stimulation and intracellular calcium overload. These findings led to the hypothesis that mutations in the cAMP signaling transduction pathway could be responsible for this disease. To that end, it was shown that cardiac somatic mutations in G coupled proteins, obtained from biopsy samples at the tachycardia's site of origin, augmented activation of cAMP. The arrhythmia phenotype was also reproduced in a rabbit model where the clinically identified mutations were expressed in the heart. These findings established that G protein dysregulation is an important mediator of clinical ventricular arrhythmias and that cardiac somatic mutations can be responsible for clinical disease.
