Thirty-five years of progress in cardiovascular research

In this overview of the achievements of the National Heart, Lung, and Blood Institute (NHLBI), the major developments in each major form of heart disease since the birth of the Institute 35 years ago are reviewed. In the case of congenital heart disease, it has become possible to establish an accurate diagnosis, often by noninvasive methods, and to correct by surgical treatment almost all congenital cardiac malformations. The major challenge now is to eliminate these disorders; this will require an understanding of the fundamental molecular basis of these lesions. Acquired valvular heart disease can also now be characterized by hemodynamic, angiographic, as well as noninvasive techniques, principally echocardiography. Surgical treatment is usually successful, but improvement in the durability of valves without thromboembolic potential remains an important challenge. While essential hypertension can now be managed pharmacologically in almost every patient and while such management reduces the excess mortality resulting from this condition, current research focuses on elucidating the underlying basis of this disorder. Atherosclerosis remains the most common cause of cardiac and vascular disease. Although its cause has not been defined, several abnormalities in lipid metabolism that play an etiologic role in many patients with atherosclerosis have been identified. The treatment of these disorders with cholesterol-binding resins, which increase the number of cellular receptors for low-density lipoprotein, and with inhibitors of the enzyme required for cholesterol biosynthesis holds considerable promise. Noninvasive techniques will be used increasingly for detection of atherosclerosis in asymptomatic persons and for determining the efficacy of therapy. The mortality resulting from acute myocardial infarction has been reduced in half by the development of coronary care units and the prompt treatment of potentially fatal ventricular tachyarrhythmias. Current research is focused on preventing pump failure by limiting infarct size; lysis of coronary thrombi now appears to be the most promising method of accomplishing this. Chronic angina pectoris can be relieved by the judicious use of three classes of drugs – organic nitrates, β-adrenergic blockers, and calcium antagonists, and two mechanical approaches – percutaneous transluminal coronary angioplasty and coronary artery bypass grafting – are usually successful in relieving angina in patients who do not respond adequately to medical management. Whether or not any of these approaches prolong life is not yet settled. Although sudden death caused by ventricular arrhythmias still claims more than one-third of a million lives annually, considerable progress has been made in understanding the genesis of these disorders. Future advances depend on the development and application of techniques for elucidating the underlying electrophysiologic mechanisms in individual patients, followed by rational selection of antiarrhythmic drugs. Considerable progress has been made in the development of cardiac pacemakers that can automatically detect and treat a variety of bradyarrhythmias and tachyarrhythmias, including ventricular fibrillation. Congestive heart failure is a common manifestation of the end-stage of almost all forms of heart disease. Treatment has been improved by use of newer diuretics and vasodilators, but substantial further progress is in the offing; newer positive inotropic agents and a variety of circulatory assist devices, including the totally implanted artificial heart as well as cardiac transplantation, all promise to be helpful in the treatment of this condition. As a consequence of research carried out during the past 35 years, much of it supported by the NHLBI, diagnosis and treatment of most patients with established heart disease is now possible. Future efforts should be directed increasingly at elucidating the underlying mechanisms of various forms of heart disease in an effort to prevent these disorders. Since abnormalities in cell biology, sometimes genetic and often involving cells other than those in the heart, play causative roles, research in the broad fields of cell biology and biochemical genetics is likely to be particularly fruitful.