Prevalence and correlates of posterior extra echocardiographic spaces in a free-living population based sample (the Framingham study)

To obtain epidemiologic information on extra echocardiographic spaces immediately posterior to the left ventricular free wall, 2,028 subjects in the original Framingham cohort study (mean age 70 +/- 7 years) and 3,624 of the offspring of the cohort (and their spouses) (mean age 44 +/- 10 years) with adequate echocardiograms were evaluated. Extra echocardiographic spaces were detected in 370 (6.5%) of the 5,652 subjects. The prevalence ranged from less than 1% in subjects in the 20- to 30-year age decade to greater than 15% for those in their 80s. Extra echocardiographic spaces tended to be more common in subjects who were older, female, obese, more hypertensive, and who had higher blood sugar levels and higher low density lipoprotein cholesterol levels (measured 8 years earlier). The high prevalence of extra echocardiographic spaces and the independent association with age (cohort and offspring), obesity (cohort and male offspring), and ventricular septal hypertrophy (cohort and male offspring) is compatible with at least 2 hypotheses among others that should be tested: (1) Subepicardial fat may often masquerade as pericardial fluid producing a posterior extra echocardiographic space, especially in obese elderly subjects. (2) Small posterior extra echocardiographic spaces may often be early markers of subclinical hypertensive heart disease.     

Blood pressure and survival after myocardial infarction: The Framingham study

Blood pressures were routinely obtained biennially from 2,336 men in the Framingham cohort over a 20 year period of follow-up study. During that time 193 men had their first myocardial infarction. Blood pressure after myocardial infarction was unrelated to survival over the next 5 years, but the blood pressure status preceding the infarction was distinctly related to survival, with hypertensive patients having almost three times the mortality of normotensive patients. These results are explained by the two-fold greater risk of death incurred by hypertensive patients who had a substantial decrease in pressure after myocardial infarction compared with that of men who remained hypertensive. The greater the decrease in pressure after myocardial infarction the greater was the mortality. With exclusion of men who experienced a reduction of more than 10 mm Hg in pressure, men with hypertension after myocardial infarction had a five-fold greater risk of mortality than that of normotensive patients.A decrease in pressure with interim myocardial infarction occurs frequently, even when the influence of age, treatment and regression toward the mean are taken into account. Men who experienced such reductions in pressure had a reduction in vital capacity (not statistically significant) and an increase in heart rate, thus suggesting that poorer myocardial function accounts for the greater mortality.     

Prevalence of submitral (anular) calcium and its correlates in a general population-based sample (the Framingham Study)

To obtain epidemiologic information on submitral calcium, 2,069 subjects in the original Framingham Study cohort (mean age 70 +/- 7 years) and 3,625 of the offspring of the cohort and their spouses (mean age 44 +/- 10 years) with adequate echocardiograms were evaluated. Submitral calcium was detected in 162 (2.8%) of the 5,694 subjects; greater than 90% of the subjects with such calcium came from the 40% of the study group greater than 59 years of age. Women were more than twice as likely to have such calcium as men. Age in both sexes, systolic blood pressure in men, and obesity in women were significantly and independently associated with submitral calcium. There was a 12-fold excess of atrial fibrillation in subjects with (20 of 162, 12%) compared with those without (53 of 5,532, 1%) submitral calcium.     

Prognosis after initial myocardial infarction: the Framingham study.

During 20 years of follow-up of 5,127 men and women initially free of coronary heart disease in the Framingham cohort, 193 men and 53 women had one or more recognized, symptomatic myocardial infarctions. An additional 45 men and 28 women had unrecognized myocardial infarctions. Subsequent mortality and morbidity including angina, reinfarction, congestive failure and sudden death were ascertained. One in five men who had a first myocardial infarction died within 1 year, a mortality rate 14 times that of those free of coronary heart disease. In men who survived the 1st year, a recognized myocardial infarction increased risk of death over the next 5 years to 23 percent, four times that of the general population. The next 5 years carried a 25 percent mortality (three times that of the general population). The prognosis was distinctly worse in women than in men chiefly because of a higher (45 percent) early mortality rate in women. Patients with recognized and unrecognized myocardial infarctions had similar survival rates after 3 years. A second myocardial infarction occurred in 13 percent of the men and in 40 percent of the women within 5 years of the first infarction. Thus, women were more prone to death and reinfarction than men. Congestive heart failure occurred as commonly as reinfarction, affliction 14 percent of the men within 5 years of the initial infarction. Once congestive failure ensued, half of the affected patients were dead within 5 years. Angina developed in one third of the patients within 5 years of their first infarction.     

Role of diabetes in congestive heart failure: the Framingham study

The incidence of congestive heart failure was determined in relation to prior diabetic status in 5,209 men and women aged 30 to 62 years followed up for 18 years in the Framingham study. Men aged 45 to 74 years had more than twice the frequency of congestive failure as their nondiabetic cohorts, and diabetic women had a fivefold increased risk. This excessive risk appears to be caused by factors other than accelerated atherogenesis and coronary heart disease. Even when patients with prior coronary or rheumatic heart disease were excluded, the diabetic subjects had a four- to fivefold increased risk of congestive heart failure. In women (but not men) with prior coronary disease, diabetes also imposed a threefold increased risk of congestive failure. Furthermore, the increased risk of heart failure in the diabetic patients persisted after taking into account age, blood pressure, weight and cholesterol values as well as coronary heart disease. Women with diabetes appeared to be especially vulnerable and, irrespective of coronary disease status, had twice the frequency of congestive heart failure as men. The excessive risk of heart failure among diabetic subjects was confined to those treated with insulin. The data suggest that diabetes is another discrete cause of congestive heart failure and that some form of cardiomyopathy is associated with diabetes, as a result of either small vessel disease or metabolic disorders.     

A general cardiovascular risk profile: the Framingham Study.

Persons at high risk of cardiovascular disease can be effectively identified from a measurement of their serum cholesterol and blood pressure, a smoking history, an electrocardiogram and a determination of glucose intolerance. One general function for identifying persons at high risk of cardiovascular disease is also effective in identifying persons at risk for each of the specific diseases, coronary heart disease, atherothrombotic brain infarction, hypertensive heart disease and intermittent claudication, even though the variables used have a different impact on each particular disease. The 10 percent of persons identified with use of this function as at highest risk accounted for about one fifth of the 8 year incidence of coronary heart disease and about one third of the 8 year incidence of atherothrombotic brain infarction, hypertensive heart disease and intermittent claudication. Hence the function provides an economic and efficient method of identifying persons at high cardiovascular risk who need preventive treatment and persons at low risk who need not be alarmed about one moderately elevated risk characteristic.     

Sudden unexpected death during ambulatory electrocardiographic monitoring: The framingham study

This report documents the clinical and electrocardiographic events of sudden unexpected death in a 52-year-old man without known heart disease during ambulatory electrocardiographic monitoring. This death occurred two and a half hours after detailed noninvasive testing, including treadmill exercise, that was unrevealing. The sequence of S-T change suggesting epicardial injury, multiform ventricular premature depolarizations, and frequent and early cycle ventricular premature depolarizations followed by ventricular tachycardia-flutter-fibrillation precipitated by an early cycle ventricular premature depolarization were documented. The delay in cardiopulmonary resuscitation in this witnessed cardiac arrest punctuates the need for widespread dissemination of the skills of cardiopulmonary resuscitation.     

Some lessons in cardiovascular epidemiology from Framingham.

Epidemiologic investigations have provided a portrait of the potential candidate for coronary heart disease. This is important because studies of the evolution of coronary disease in the general population reveal that it is a common disease that frequently attacks without warning, can be silent in its most dangerous form and can present with sudden death as the first symptom. Progress in identifyin- persons in jeopardy and the factors needing correction makes it theoretically possible to interrupt the chain of factors that eventuate in this disease. Coronary disease does not really begin with crushing chest pain, pulmonary edema, shock, angina or ventricular fibrillation, but rather with more subtle signs like a poor coronary risk profile. The risk factors can be treated quantitatively as ingredients of a cardiovascular risk profile and their joint effect estimated. An efficient practicable set of variables for this purpose is a casual blood test for cholesterol and sugar, a blood pressure determination, an electrocardiogram and a cigarette smoking history. With this set of variables the risk of coronary heart diseases can be estimated over a 30-fold range and 10 percent of the asymptomatic population identified in whom 25 percent of the coronary disease, 40 percent of the occlusive peripheral arterial disease and 50 percent of the strokes and congestive heart failure will evolve. The periodic use of the electrocardiogram at rest and after exercise in persons with a poor risk profile can demonstrate persons with asymptomatic ischemic cardiomyopathy due to advanced coronary artery disease. Most cases of angina pectoris or myocardial infarction represent medical failures; the conditions should have been detected years earlier for preventive management. About 30 percent of patients with infraction will shortly experience new angina, have an annual death rate of 4 percent and a fourfold increased risk of sudden death. Reinfarction will occur at an annual rate of 6 percent, and half the recurrences will be fatal. Congestive heart failure must be expected at 10 times and strokes at 5 times the rate found in the general population. Although no major innovations are required to identify candidates for coronary disease and to estimate their risk, we have much to learn about motivating changes in behavior to control risk factors. Approaches to prevention of coronary heart disease include public health measures to alter the ecology in favor of cardiovascular health, preventive medicine directed at highly vulnerable candidates and hygienic measures initiated by an informed public in its own behalf.     

Functional bundle branch block: Discordant response of right and left bundle branches to changes in heart rate

Faster heart rates shorten refractoriness more in some tissues than in others. This study investigates whether faster heart rates shorten relative refractoriness more in the right than left bundle branch in humans. Premature atrial stimulation at 2 or more basic cycle lengths was performed in 314 patients with no evidence of atrioventricular conduction system disease. In 10 patients, both functional right and left bundle branch block (BBB) developed with premature atrial stimulation. Functional right BBB occurred at the longer basic cycle length, and functional left BBB at the shorter cycle length in 8 patients. In 2 patients functional right and functional left BBB were present at the same cycle length, but functional left BBB occurred at a shorter premature atrial coupling interval. For all patients, the mean functional right bundle branch relative refractoriness was 438 ms at a basic cycle length of 847 ms, and functional left bundle branch relative refractoriness was 357 ms at a cycle length of 622 ms (p <0.01). The HV interval was 45 ± 15 ms at control and increased with functional left BBB to 77 ± 19 ms (p <0.01), but not with functional right BBB. Thus, relative refractoriness of the right and left bundle branches are rate-dependent and discordant. At longer cycle lengths, relative refractoriness of the right bundle branch is greater than that of the left bundle branch, and at shorter cycle lengths relative refractoriness of the left bundle branch is greater than that of the right bundle branch. The relative refractory period curves “cross over” and can explain the presence of both functional right and left BBB in the same patient.     

Exercise-induced bundle branch block

Exercise-induced bundle branch block (BBB) is poorly understood. An investigation was made of its clinical, electrocardiographic, coronary angiographic, and myocardial scintigraphic characteristics, with follow-up data in 16 patients, aged 59 ±9 (mean ± standard deviation) years, 11 who had left BBB and 5 who had right BBB. Fourteen had a preexisting baseline electrocardiographic abnormality; 11 had either incomplete BBB or nonspecific intraventricular conduction delay. Heart rates at onset of exercise BBB varied from 70 to 166 beats/min and in 9 patients the rates at BBB onset and offset appeared to be related, occurring within 8 beats/min of each other. Coronary artery disease (CAD) was diagnosed in 10 patients, cardiomyopathy in 2, and probable coronary spasm in 2. One patient had ventricular arrhythmias of uncertain origin, and 1 appeared to have no cardiac disease. Three patients had reversible thallium perfusion defects consistent with ischemia concurrent with developing BBB. The 3 patients in whom exercise BBB persisted all had CAD. Over a mean of 28 months of follow-up, only 1 patient had a morbid cardiac event—nonfatal myocardial infarction—and 2 died from noncardiac causes. Thus, exercise BBB primarily occurs in the context of cardiac disease, most commonly CAD, and concurrent ischemia may be demonstrable; the presence of “rate relation” does not militate against CAD.     

Electrocardiography and electrophysiology are (or should be) friends

The anginal status of the Framingham cohort was ascertained in a uniform manner during 20 years of follow-up studies. There were 74 men and 84 women with newly acquired angina that was not complicated with other manifestations of coronary heart disease. Remission of new angina pectoris for at least 2 years occurred in 32 percent of the men and 44 percent of the women. In angina that had persisted for several years, the subsequent remission rates were lower (14 percent for men and 19 percent for women). The similarity of coronary risk attributes of subjects with transient or persistent angina supports the hypothesis that both conditions may be true manifestations of coronary artery disease. Persistence of symptoms seems to indicate a more severe form of the disease characterized by nonspecific S-T segment or T wave abnormalities. It is associated with a greater incidence of myocardial infarction and death than in subjects with transient angina. The generally high remission rates must be taken into account in considering drastic surgical or medical remedies for clinical angina pectoris. Also, other possible causes for the chest pain should be sought.     

Excess mortality and morbidity associated with right bundle branch and left anterior fascicular block

Excess mortality and morbidity associated with right bundle branch and left anterior fascicular block were evaluated in 108 patients with block (age 74 +/- 10 years, 69% male) and 108 age- and sex-matched control patients with normal conduction. Clinical characteristics were similar initially except for more congestive heart failure in patients with block. Life table analysis revealed a higher 12 year mortality with block, even after omitting patients with moderate or severe congestive heart failure (risk ratio 1.47, p less than 0.05). Compared with control subjects, the group of patients with block had more sudden death and deaths of unknown cause, but a similar number of noncardiac and diagnosed cardiac deaths. More patients with block developed new second and third degree atrioventricular block or new overt coronary artery disease, but this finding did not support prophylactic pacing in asymptomatic patients. The importance of internal controls in assessing the natural history of clinical and electrocardiographic abnormalities is emphasized.     

Coronary arteriographic findings in symptomatic right bundle branch block

Of 5,132 consecutive patients who had coronary arteriography for chest pain, 103 (2%) had right bundle branch block (RBBB), 66 (64%) of whom had no electrocardiographic evidence of concomitant myocardial infarction (MI); 23 patients had evidence of MI of the inferior wall, 8 of the anterior wall and 6 of the lateral wall. The incidence, location or severity of coronary artery disease (CAD) in patients with RBBB alone were not significantly different from those in 110 similarly symptomatic patients with normal ECGs. However, significantly more left ventricular contraction abnormalities, especially in the anteroapical area, were found in patients with RBBB (p less than 0.01). Similarly, patients with RBBB and inferior MI, compared with 60 similarly symptomatic patients with inferior MI without RBBB, showed no significant differences in location, incidence or severity of CAD. However, more left ventricular contraction abnormalities in the apical area were found in patients with RBBB (p less than 0.025). Thus, the presence of RBBB does not suggest more severe or extensive CAD; however, RBBB does predict more left ventricular contraction abnormalities.     

Chronic right bundle branch block and left posterior hemiblock: Clinical, electrophysiologic and prognostic observations

Twenty-one patients with long-term right bundle branch block and left posterior hemiblock were studied electrophysiologically and then followed up prospectively. The group consisted of 19 men and 2 women aged 61 ± 2.7 years (mean ± standard error of the mean). The majority of patients had either hypertensive cardiovascular disease (48 percent) or primary conduction disease (33 percent). Initial electrophysiologic studies revealed A-H intervals of 58 to 152 msec (mean 98 ±7.7) and H-V intervals of 40 to 80 msec (mean 52 ± 2.1). Six patients (29 percent) had prolonged H-V intervals. The follow-up period ranged from 91 to 1,231 days (mean 671 ± 68). Three of 21 patients (14 percent) needed a permanent pacemaker after development of the following symptomatic conduction disease: sinoatrial block on day 3 of follow-up; second degree atrioventricular (A-V) block, site undetermined, on day 118; and second degree A-V block proximal to the His bundle on day 398. One patient died suddenly (on day 571), and two others died of noncardiac causes.

In conclusion, combined right bundle branch block and left posterior hemiblock was associated with less trifascicular disease than reported previously. The clinical course of most of the patients was benign and the incidence of sudden death was relatively small. Symptomatic conduction disease occurred but could be definitely related to trifascicular disease in only one patient. These short-term data suggest that prophylactic pacemaker insertion is not routinely indicated in patients with chronic right bundle branch block and left posterior hemiblock.