Douglas R. Rosing

Sudden death in young athletes.

The causes of sudden and unexpected death in 29 highly conditioned, competitive athletes, ages 13-30 years, are summarized. Sudden death occurred during or just after severe exertion on the athletic field in 22 of the 29 athletes. Structural cardiovascular abnormalities were identified at necropsy in 28 of the 29 athletes (97%), and in 22 (76%) were almost certainly the cause of death. The most common cause of death in this series was hypertrophic cardiomyopathy, which was present in 14 athletes. Other cardiovascular abnormalities that occurred in more than one athlete were anomalous origin of the left coronary artery from the right (anterior) sinus of Valsalva, idiopathic concentric left ventricular hypertrophy, coronary heart disease and ruptured aorta. Cardiac disease was suspected during life in only seven of the 29 patients, and in only two of the seven was the correct diagnosis made clinically. Hence, in this series of young athletes, sudden death was usually due to structural cardiovascular disease...

Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography.

To assess left ventricular (LV) diastolic filling at rest in patients with coronary artery disease (CAD), we analyzed high-resolution time-activity curves (10-20 msec/frame) obtained from gated radionuclide angiograms in 231 patients. Peak LV filling rate (PFR), expressed in end-diastolic volumes per second (EDV/sec), was subnormal in CAD patients (1.8 +/- 0.6 [+/- SD] vs normal mean of 3.3 +/- 0.6, p les than 0.001) and time to PFR (TPFR), measured from end-systole to PFR, was prolonged (171 +/- 41 msec vs normal mean of 136 +/- 23 msec, p less than 0.001). These indexes were also abnormal in the 141 patients with normal resting LV ejection fraction (PFR = 2.1 +/- 0.5 EDV/sec; TPFR = 175 +/- 36 msec) and in 123 patients without Q waves on the ECG (PFR = 2.1 +/- 0.5 EDV/sec; TPFR = 168 +/- 38 msec). Abnormal LV filling at rest (PFR less than 2.5 EDV/sec or TPFR greater than 180 msec) was found in 91% of all patients with CAD, 86% of patients with normal resting LV ejection fractions, 85% of patients without Q waves, and 82% of patients with normal resting LV ejection fraction, no resting regional wall motion abnormalities and no Q waves. Thus, LV diastolic filling, evaluated noninvasively by radionuclide angiography, is abnormal in a high percentage of patients with CAD at rest independent of LV systolic function or previous myocardial infarction.

Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures.

To study the mechanism and hemodynamic significance of myocardial ischemia in hypertrophic cardiomyopathy, 20 patients (nine with resting left ventricular outflow tract obstruction greater than or equal to 30 mm Hg) with a history of angina pectoris and angiographically normal coronary arteries underwent a pacing study with measurement of great cardiac vein flow, lactate and oxygen content, and left ventricular filling pressure. Compared with 28 control subjects without hypertrophic cardiomyopathy, their resting coronary blood flow was higher (91 +/- 27 vs 66 +/- 17 ml/min; p less than .001) and their coronary resistance was lower (1.13 +/- 0.38 vs 1.55 +/- 0.45 mm Hg/ml/min; p less than .001). Left ventricular end-diastolic pressure (16 +/- 6 vs 11 +/- 3 mm Hg; p less than .001) and pulmonary arterial wedge pressure (13 +/- 5 vs 7 +/- 3 mm Hg; p less than .001) were significantly higher in patients with hypertrophic cardiomyopathy. During pacing, coronary flow rose in both groups, although coronary and myocardial hemodynamics differed greatly. In contrast to the linear increase in flow in control subjects up to heart rate of 150 beats/min (66 +/- 17 to 125 +/- 28 ml/min), patients with hypertrophic cardiomyopathy demonstrated an initial rise in flow to 133 +/- 31 ml/min at an intermediate heart rate of 130 beats/min. At this point, 12 of 20 patients developed their typical chest pain. With continued pacing to a heart rate of 150 beats/min, mean coronary flow fell to 114 +/- 29 ml/min (p less than .002), with 18 of 20 patients experiencing their typical chest pain and metabolic evidence of myocardial ischemia. This fall in coronary flow was associated with a substantial rise in left ventricular end-diastolic pressure (30 +/- 9 mm Hg immediately after peak pacing). In the 14 patients whose coronary flow actually fell from intermediate to peak pacing, the rise in left ventricular end-diastolic pressure in the same interval was greater than that of the six patients whose flow remained unchanged or increased (11 +/- 8 vs 2 +/- 2 mm Hg; p less than .01). In addition, despite metabolic and hemodynamic evidence of myocardial ischemia, the arteriovenous O2 difference actually narrowed at peak pacing. Thus most patients with hypertrophic cardiomyopathy achieved maximum coronary vasodilation and flow at modest increases in heart rate. Elevation in left ventricular filling pressure, probably related to ischemia-induced changes in ventricular compliance, was associated with a decline in coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Angina caused by reduced vasodilator reserve of the small coronary arteries

To study the mechanism of chest pain in patients vvith insignificant large vessel coronary artery disease, 22 patients underwent great cardiac vein flow, coronary resistance and lactate determinations at rest and with coronary sinus pacing followed by coronary arteriography. Nine patients experiencing chest pain with pacing demonstrated significantly lesser increase in flow from base-line values (45 ± 30versus86 ± 50% [mean ± standard deviation], p After administration of ergonovine, 0.15 mg intravenously, 2 of 20 patients experienced spontaneous chest pain, which was associated with the greatest decrease in flow ( - 13 and -21%, respectively) and increase in resistance ( + 26 and +39%, respectively) of any patient. Pacing resulted in chest pain in 10 of the remaining 18 patients, including 5 patients who had not experienced chest pain during the control pacing study. Although none of these patients exhibited significant epicardial coronary artery narrowing on arteriography, their flow increased less (38 ± 12 versus 126 ± 68%, p These findings suggest that some patients with atypical chest pain have inappropriate coronary arteriolar or small coronary artery constriction with abnormal vasodilator reserve in response to atrial pacing. The abnormality can be unmasked or exacerbated in some patients by vasoconstrictor stimuli, but cannot be identified with standard angiographic assessment of “spasm” because abnormal vasoconstriction occurs in vessels too small to be visualized by angiography.

Effects of verapamil on left ventricular systolic function and diastolic filling in patients with hypertrophic cardiomyopathy.

Verapamil improves exercise capacity in patients with hypertrophic cardiomyopathy (HCM), but its mechanisms of action are unknown. We examined the effects of oral verapamil (320–480 mg/day) on resting left ventricular (LV) systolic and diastolic function in patients with HCM. High‐temporal‐resolution time‐activity curves from gated technetium‐99m radionuclide angiograms were analyzed before and after verapamil therapy in 40 patients, of whom 16 were also studied during propranolol therapy (80–960 mg/day). All but one patient had normal or supranormal systolic function, but 70% had evidence of diastolic dysfunction, defined as peak LV filling rate (PFR) < 2.5 end‐diastolic volumes (EDV)/sec or time to PFR > 180 msec. Verapamil did not change LV ejection fraction, peak ejection rate or ejection time, but did increase PFR (control 3.3 ± 1.0 EDV/sec, verapamil 4.1 ± 1.1 EDV/sec; p < 0.001) and reduce time to PFR (control 187 ± 56 msec, verapamil 159 ± 34 msec; p < 0.001). Only 30% of patients had evidence of diastolic dysfunction during verapamil. In contrast, propranolol did not change LV ejection fraction, PFR or time to PFR, but did prolong ejection time and reduce peak ejection rate. Thus, LV diastolic filling is abnormal in a high percentage of patients with HCM, and verapamil normalizes or improves these abnormalities without altering systolic function. This mechanism may contribute to the clinical improvement of many HCM patients during verapamil therapy.

Sensitivity, specificity and predictive accuracy of radionuclide cineangiography during exercise in patients with coronary artery disease. Comparison with exercise electrocardiography.

Noninvasive radionuclide cineangiography permits the assessment of global and regional left ventricular function during intense exercise. To assess the sensitivity of the technique in detecting coronary artery disease, we studied 63 consecutive patients with ≥ 50% stenosis of at least one coronary artery. Fiftynine (94%) had regional dysfunction with exercise; 56 (89%) developed lower-than-normal ejection fractions during exercise. When both regional dysfunction and subnormal ejection fractions are considered together, the sensitivity was 95%. Each patient also underwent exercise electrocardiography to either angina or 85% of predicted maximal heart rate. Of the 42 patients who developed angina during exercise electrocardiography, 26 (62%) developed ≥1 mm ST-segment depression; four additional patients (10%) had Q waves diagnostic of previous myocardial infarction. In contrast, 39 (93%, p < 0.001) developed regional dysfunction during radionuclide study, and one additional patient developed a subnormal ejection fraction without regional dysfunction. To assess specificity, we studied 21 consecutive patients with chest pain who had normal coronary arteries. None developed regional dysfunction; ejection fraction increased in all to levels within the range previously defined as normal. The predictive accuracy in this symptomatic population was 100%. We conclude that radionuclide cineangiography is highly sensitive (more so than exercise electrocardiography), predictive and specific in detecting patients with coronary artery disease.

Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: short- and long-term effects.

Verapamil improves exercise tolerance and decreases symptoms in many patients with hypertrophic cardiomyopathy. The mechanisms responsible for these effects are not completely understood, although previous studies indicate that verapamil enhances left ventricular relaxation and diastolic filling in such patients. To investigate the association between changes in left ventricular filling and exercise tolerance after verapamil, we studied 55 patients with hypertrophic cardiomyopathy by radionuclide angiography and graded treadmill testing before and after 1 to 4 weeks of therapy with orally administered verapamil, 320 to 640 mg/d. The verapamil-induced increase in peak left ventricular filling rate at rest (from 3.1 +/- 1.3 to 3.7 +/- 1.3 end-diastolic volumes/sec; p less than .001) was associated with an increase in exercise tolerance (from 5.9 +/- 3.6 to 8.7 +/- 4.7 min; p less than .001); exercise capacity increased in 34 of 43 patients (79%) manifesting an increase in peak filling rate but only one of 12 patients (8%) with unchanged or decreased peak filling rate (p less than .001). This initial trend persisted in 25 patients studied after 1 year of therapy; 11 of 16 patients (69%) with a persistent increase in peak filling rate had persistent improvement in exercise tolerance relative to preverapamil values, compared with only one of nine patients (11%) in whom peak filling rate was unchanged or decreased relative to preverapamil levels (p less than .02). Verapamil withdrawal after 1 to 2 years in 24 patients resulted in reduction in peak filling rate (p less than .001) and was associated with deterioration in exercise tolerance in 17 patients (71%). Hence, verapamil-induced changes in left ventricular peak filling rate were associated significantly with objective symptomatic improvement. These data support the concept that enhanced left ventricular diastolic filling is an important mechanism contributing to the clinical improvement experienced by many patients with hypertrophic cardiomyopathy during therapy with verapamil.

Aortic Dilatation and Dissection in Turner Syndrome

Background— The risk for aortic dissection is increased among relatively young women with Turner syndrome (TS). It is unknown whether aortic dilatation precedes acute aortic dissection in TS and, if so, what specific diameter predicts impending deterioration. Methods and Results— Study subjects included 166 adult volunteers with TS (average age, 36.2 years) who were not selected for cardiovascular disease and 26 healthy female control subjects. Ascending and descending aortic diameters were measured by magnetic resonance imaging at the right pulmonary artery. TS women were on average 20 cm shorter, yet average aortic diameters were identical in the 2 groups. Ascending aortic diameters normalized to body surface area (aortic size index) were significantly greater in TS, and ≈32% of TS women had values greater than the 95th percentile of 2.0 cm/m2. Ascending diameter/descending diameter ratios also were significantly greater in the TS group. During ≈3 years of follow-up, aortic dissections occurred in 3 women with TS, for an annualized rate of 618 cases/100 000 woman-years. These 3 subjects had ascending aortic diameters of 3.7 to 4.8 cm and aortic size indices >2.5 cm/m2. Conclusions— The risk for aortic dissection is greatly increased in young women with TS. Because of their small stature, ascending aortic diameters of <5 cm may represent significant dilatation; thus, the use of aortic size index is preferred. Individuals with a dilated ascending aorta defined as aortic size index >2.0 cm/m2 require close cardiovascular surveillance. Those with aortic size index ≥2.5 cm/m2 are at highest risk for aortic dissection.

Exercise-induced left ventricular dysfunction in symptomatic and asymptomatic patients with aortic regurgitation: assessment with radionuclide cineangiography.

In patients with aortic regurgitation,, left ventricular dysfunction at rest, which is associated with a poor long-term prognosis, often develops before severe symptoms. To determine whether evidence of left ventricular dysfunction could be detected before it appeared at rest, 43 patients with severe aortic regurgitation were studied using radionuclide cineangiography during exercise. In 30 normal subjects, left ventricular ejection fraction increased during exercise (57 +/- 1 percent [mean +/- standard error] at rest, 71 +/- 2 percent during exercise, P less than 0.001). In contrast, among 21 symptomatic patients, ejection fraction was normal at rest in 14 patients (average 47 +/- 2 percent) but normal during exercise in only one patient (average 38 +/- 2 percent, P less than 0.001). Ejection fraction was normal at rest in 21 of 22 asymptomatic patients (average 62 +/- 2 percent) but was normal during exercise in only 13 (average 57 +/- 3 percent, P less than 0.001). Thus, exericse-induced left ventricular dysfunction can precede symptoms and dysfunction at rest. Radionuclide assessment of left ventricular function during exercise may prove valuable in sequentially following the state of left ventricular function in patients before the onset of symptoms or of irreversible left ventricular failure.

Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve.

Thirty-three patients with chest pain despite angiographically normal coronary arteries underwent both coronary flow studies during pacing and resting and exercise gated blood pool scintigraphy. During atrial pacing after administration of ergonovine, those patients developing their typical chest pain demonstrated significantly lower great cardiac vein flow (97 +/- 31 vs 150 +/- 33 ml/min, p less than .001), higher coronary resistance (1.27 +/- 0.43 vs 0.77 +/- 0.18 mm Hg/ml/min, p less than .005), and less lactate consumption (30.5 +/- 22.0 vs 69.7 +/- 41.1 mM . ml/min, p less than .005) and a higher left ventricular end-diastolic pressure after pacing (20 +/- 4 vs 12 +/- 1, p less than .001) compared with those without pain and in the absence of significant luminal narrowing of the epicardial coronary arteries. The 26 patients with abnormal vasodilator reserve demonstrated reduced left ventricular ejection fraction during exercise (58 +/- 8%) compared with the seven patients with appropriate vasodilator reserve (66 +/- 4%, p less than .05) and with a group of 52 control patients of similar age and sex distribution and free of known heart disease (66 +/- 10%, p less than .001). In addition, 12 of the 26 patients with abnormal vasodilator reserve demonstrated exercise-induced regional wall motion abnormalities. Many of these patients also manifested impaired left ventricular diastolic filling at rest compared with the control subjects (peak filling rate 2.6 +/- 0.7 vs 3.2 +/- 0.7 end-diastolic volume/sec, p less than .005). Thus, patients with chest pain resulting from abnormal vasodilator reserve demonstrate abnormalities of left ventricular systolic and diastolic function suggestive of myocardial ischemia.