Heart Rate-systolic Blood Pressure Product Research Articles

The Relation of Arm Exercise Peak Heart Rate to Stress Test Results and Outcome.

Arm exercise is an alternative to pharmacologic stress testing for >50% of patients unable to perform treadmill exercise, but no data exist regarding the effect of attained peak arm exercise heart rate on test sensitivity. Thus, the purpose of this investigation was to characterize the relationship of peak arm exercise heart rate responses to abnormal stress test findings, coronary revascularization, and mortality in patients unable to perform leg exercise. From 1997 until 2002, arm cycle ergometer stress tests were performed in 443 consecutive veterans age 64.1 yr (11.0 yr) (mean (SD)), of whom 253 also underwent myocardial perfusion imaging (MPI). Patients were categorized by frequency distributions of quartiles of percentage age-predicted peak heart rate (APPHR), heart rate reserve (HRR), and peak heart rate-systolic blood pressure product (PRPP). Exercise-induced ST-segment depression, abnormal MPI findings, coronary revascularization, and 12.0-yr (1.3 yr) Kaplan-Meier all-cause and cardiovascular mortality plots were then characterized by quartiles of APPHR, HRR, and PRPP. A reduced frequency of abnormal arm exercise ECG results was associated only with the lowest quartile of APPHR (≤69%) and HRR (≤43%), whereas higher frequency of abnormal MPI findings exhibited an inverse relationship trend with lower APPHR (P = 0.10) and HRR (P = 0.12). There was a strong inverse association of APPHR, HRR, and PRPP with all-cause (all P ≤ 0.01) and cardiovascular (P < 0.05) mortality. The frequency of coronary revascularization was unrelated to APPHR or HRR. Arm exercise ECG stress test sensitivity is only reduced at ≤69% APPHR or ≤43% HRR, whereas arm exercise MPI sensitivity and referral for coronary revascularization after arm exercise stress testing are not adversely affected by even a severely blunted peak heart rate. However, both all-cause mortality and cardiovascular mortality are strongly and inversely related to APPHR and HRR.

Effects of chronic smoking on exercise tolerance and on heart rate-systolic blood pressure product in young healthy adults

Smoking is a major cause of cardiovascular disease and mortality. Smoking-related deaths in Greece account for 23%, whereas 41% of young Greeks are smokers, the highest percentage in Europe. The purpose of this study was to examine the effects of chronic smoking on the rate-pressure product and exercise tolerance in young, healthy male smokers. Forty-two smokers and 51 nonsmokers were selected from a population of 543 students based on their age, sex, body mass index, physical fitness, smoking habit and health status. All participants were tested with the standard Bruce treadmill protocol. The rate-pressure product was obtained at rest and during exercise at a given submaximal workload. The evaluation of exercise tolerance was based on peak workload achieved and maximal exercise test duration. The smokers had a higher rate-pressure product at rest (P<0.001) due to their higher resting heart rate (P<0.001). Resting values of blood pressure did not differ significantly between the two groups. During exercise, smokers had a greater rate-pressure product (P<0.001), mainly due to their significantly higher systolic blood pressure (P=0.008). The smokers had a higher submaximal heart rate (P=0.005), but the differences in heart rate between groups were reduced for smokers during exercise when compared to rest. The smokers' exercise tolerance was impaired and their maximal exercise test duration time was significantly shorter (P<0.001). Chronic smoking was found to affect young male smokers' cardiovascular fitness, impairing the economy and decreasing the capacity of their circulatory system.

‘Warm-up’ phenomenon in diabetic patients with stable angina treated with diet or sulfonylureas

Classic sulfonyloureas (SUs) are known to attenuate ischaemic preconditioning. Gliclazide is an SU agent believed to be more protective. We assessed the effects of diet, glibenclamide, or gliclazide on the warm-up effect in type 2 diabetic patients with stable angina. The study group consisted of 64 men, aged 54+/-5 years: 17 patients without diabetes (G I) and 47 diabetic patients: 16 patients treated with glibenclamide (G II), 16 with gliclazide (G III) and 15 patients treated with diet (G IV). After the baseline positive exercise test (ET1), all patients reexercised after 30-min rest (ET2). We analysed exercise duration (ED, s), time to 1 mm ST depression (T-STD, s), max STD (mm), heart rate-systolic blood pressure product at 1 mm STD, or ischaemic threshold (mmHg/min x 100) and the total ischaemic time (s). In G I, all analysed variables improved significantly during ET2 relative to ET1. Glibenclamide (G II) completely abolished the protective effect of exercise-induced ischaemia because only ED increased during ET2 (431 vs. 451, P<0.05). In G III, however, ED (486 vs. 537, P<0.001), T-STD (364 vs. 388, P<0.05) and max STD (2.5 vs. 2.0, P<0.05) improved significantly during ET2, whereas ischaemic threshold and total ischaemic time did not (PNS). In G IV, similar to G I, all variables improved significantly during ET2 relative to ET1. Warm-up effect is preserved in diabetic patients with stable angina treated with diet, partially preserved in gliclazide-treated and abolished in glibenclamide-treated patients.

Reply to Kargar and Aazami

We thank Kargar and Aazami [1] for their interest in our recent article on flow dynamics and wall shear stress (WSS) in the left internal thoracic artery (LITA) [2]. In this study we show that the LITA has a marked adaptability to flow dynamics with a clear propension to adequate WSS and crosssectional area to flow requirements. Two modifications take place into proximal LITA used as a composite Y-graft: (1) a ‘passive’ increase in blood flow due to the lower resistance of the parallel vascular circuit represented by the Y-graft, as expressed by the Kirchoff’s 2nd law, and (2) an ‘active’ increase of proximal LITA diameter related to the higher average peak velocity and blood flow that stimulate the synthetic and secretory functions of endothelial cells, modulating the production of nitric oxide and endothelin-1 to obtain proximal LITA dilatation. Finally also the flow pattern could have a role in the production of vasoactive substances by vascular endothelial cells, presenting the proximal part of LITAY-graft a diastolic-predominant peak of flow velocity, probably related to the reduced vascular resistance of the parallel vascular circuit. In conclusion our study shows that in composite Y-graft the proximal LITA is able to actively adapt its dimension to the flow demand, probably through the release of endothelial vasoactive mediators, consequence of higher values of WSS. This process of adaptation begins immediately after the operation because of the passive increase of blood flow due to the lower vascular resistance of the Y-graft system. Kargar and Aazami seem to be skeptical about the adaptability of the LITA to increased myocardial blood flow requirements. However we have shown that soon after the operation the LITA used as a Y-graft can significantly increase blood flow in response to conditions of increased MVO2, keeping normal the O2 supply-to-demand ratio. We obtained these data measuring blood flow in Y-graft both at rest and during atrial pacing at the 85% of the patient age-predicted maximum, considering the heart rate-systolic blood pressure product an indirect index of MVO2 [3]. Both the afore mentioned functional data and the favourable clinical results coming from LITA used as a Y-graft [4] should comfort Kargar and Azami about the safety and afficacy of the LITA in Y-graft configuration. We thank again Kargar and Aazami for their interest in our paper.

Effects of graded-release diltiazem versus ramipril, dosed at bedtime, on early morning blood pressure, heart rate, and the rate-pressure product

Background Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early morning period, a time when both morbid and mortal cardiovascular events are increased compared to other times of the day. Methods We studied the effects of a graded-release delivery system of diltiazem (diltiazem HCL extended release tablets) versus ramipril, both dosed at bedtime, on blood pressure (BP), heart rate, and the heart rate-systolic BP product during the first 4 hours after awakening in a double-blind, titration-to-effect trial. There were 261 men and women enrolled in the trial with an untreated sitting diastolic BP of 90 to 109 mm Hg and ambulatory daytime diastolic BP of 85 to 109 mm Hg. Patients were randomized to either diltiazem extended release (ER) tablets each evening (240 mg titrated to 360 mg and to 540 mg) or ramipril each evening (5 mg titrated to 10 mg and to 20 mg). Early morning assessments of BP, heart rate, and the heart rate-systolic BP product were performed using 24-hour ambulatory recordings after 10 weeks of therapy. Results In each therapeutic group, 76% of patients were titrated to the highest possible dose. After 10 weeks of treatment, reductions in early morning BP by diltiazem ER tablets were significantly greater (−18/−15 mm Hg) than reductions by ramipril (−13/−8 mmHg , P < .005 for systolic BP and P < .001 for diastolic BP). Diltiazem ER tablets also led to greater reductions in morning heart rate and the heart rate-pressure product compared to ramipril. Reductions in mean 24-hour diastolic BP, heart rate, and the rate-pressure product were greater in patients treated with diltiazem ER tablets compared to ramipril, while reductions in 24-hour systolic BP were similar in each group. The observed adverse effects were not serious and incidences were similar for the 2 treatment groups. Conclusions These data demonstrate that bedtime administration of diltiazem ER, an agent designed to parallel the circadian rhythm of BP and heart rate, led to significantly greater early morning hemodynamic effects compared to the angiotensin-converting enzyme inhibitor ramipril, also dosed in the evening.

Effects of heart rate on phasic Y-graft blood flow and flow reserve in patients with complete arterial myocardial revascularizaton: an intravascular Doppler catheter study.

It is not well established whether the blood flow of arterial composite Y-grafts can efficiently respond to the flow demand of the coronary system early postoperatively. The aim of this study was to evaluate if soon after the operation, arterial composite Y-grafts can increase blood flow in response to an increase in myocardial oxygen consumption (MVO2). Twenty-seven patients who received complete arterial myocardial revascularization using the left internal thoracic artery (LITA) and the radial artery (RA) as composite Y-graft gave their consent to a pre-discharge coronary angiography and intravascular flow velocity measurements using a Doppler guide wire. Flow measurements were performed in the LITA main stem, the distal LITA and the RA, both at rest and during atrial pacing at the 85% of the patient age-predicted maximum. The heart rate-systolic blood pressure product was considered as an indirect index of MVO2. Hyperemic flow was determined after injection of adenosine. The flow reserve (FR) was defined as the ratio of blood flow during maximal hyperemia (Qmax) to baseline flow (Qbasal). Atrial pacing increased MVO2 significantly (P<0.000). None of the patients developed ischemic S-T segment modifications or complained of chest pain. Q(basal) increased significantly in the LITA main stem (P=0.001), distal LITA (P=0.041) and RA (P=0.004) while Qmax did not change significantly. As a consequence, the FR decreased in the LITA main stem (P=0.002), distal LITA (P<0.000) and RA (P<0.000) but was not completely exhausted. Soon after the operation, arterial composite Y-grafts can significantly increase blood flow in response to conditions of increased MVO2, keeping normal the myocardial O2 supply-to-demand ratio.

Preventing increases in early-morning blood pressure, heart rate, and the rate-pressure product with controlled onset extended release verapamil at bedtime versus enalapril, losartan, and placebo on arising

Background Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early-morning period, a time when both morbid and mortal cardiovascular events are increased compared with other times of the day. Methods We studied the effects of a chronotherapeutic delivery system of verapamil (controlled-onset extended release [COER]-24 system) dosed at bedtime versus conventional morning administration of both enalapril and losartan on the blood pressure (BP), heart rate, and the heart rate systolic BP product during the first 4 hours after awakening in a placebo-controlled, forced-titration trial. There were 357 men and women enrolled in the trial with an untreated sitting diastolic BP of 95 to 114 mm Hg and ambulatory daytime diastolic BP ≥85 mm Hg. Patients were randomized to either COER-verapamil hydrochloride each evening (240 mg titrated to 360 mg), enalapril each morning (10 mg titrated to 20 mg), losartan each morning (50 mg titrated to 100 mg), or placebo. Early morning assessments of BP, heart rate, and the heart rate systolic BP product were performed by use of 24-hour ambulatory recordings after 4 weeks (low dose) and 8 weeks (high dose) of therapy. Results Results were similar at weeks 4 and 8 for all treatment groups except that the magnitude of change was greater at week 8. After 8 weeks of treatment, reductions in early morning BP by COER-verapamil were significantly greater (−15/−10 mm Hg) than enalapril (−9/−7 mm Hg, P <.01) and losartan (−8/−5 mm Hg, P <.001). COER-verapamil also led to greater reductions in morning heart rate, the rate-pressure product, and the rate-of-rise of BP compared with the other 2 active treatment groups. Reductions in mean 24-hour BP were greater in patients treated with COER-verapamil compared with placebo and losartan, and similar to reductions in patients treated with enalapril. Conclusions Bedtime administration of an agent designed to parallel the circadian rhythm of BP and heart rate led to significantly greater early morning hemodynamic effects compared with other conventional once-daily antihypertensive agents dosed in the morning. (Am Heart J 2002;144:657-65.)

Myocardial perfusion imaging findings and the role of adenosine in the warm-up angina phenomenon

OBJECTIVESThis study examined the roles of myocardial perfusion and adenosine in warm-up angina.BACKGROUNDIn warm-up angina, neither the role of an adenosine-mediated mechanism, as is found in experimental ischemic preconditioning, nor of increased myocardial perfusion is well defined.METHODSIn substudy A, a single-photon emission computed tomography (SPECT)-thallium-201 exercise test was performed by 12 subjects with ischemic heart disease on three occasions one week apart. The third test was preceded by a warm-up test. The extent of the thallium deficit and its intensity on the third test were compared with the baseline tests controlling for the heart rate-systolic blood pressure product (RPP) at thallium injection. In substudy B, 12 similar subjects did two successive exercise tests at two separate sessions and received the adenosine antagonist, aminophylline (intravenous 5 mg/kg bolus and 0.9 mg/kg/h infusion) at one session, and equivalent saline at the other session. Change in ischemic threshold (RPP at 1 mm ST segment depression) and in maximum ST depression adjusted for RPP were analyzed.RESULTSIn substudy A, despite a significant attenuation of electrocardiogram indexes of myocardial ischemia between the baseline and third (warmed-up) tests, the thallium extent deficits (20.8 ± 15.1% and 16.8 ± 12.4%) and intensity deficits (41.2 ± 12.6% and 39.3 ± 12.6%) did not differ significantly. In substudy B, the increase in ischemic threshold on re-exercise was unaffected by aminophylline. Adjusted maximum ST depression even decreased to a greater extent on re-exercise with aminophylline (by 51 ± 21%) than with saline (by 32 ± 19%) (p = 0.012).CONCLUSIONSWhile warm-up angina is associated with a significant attenuation of exercise electrocardiogram indexes of ischemia, it is unaccompanied by significant changes in SPECT perfusion and does not appear to be mediated by an adenosine-dependent mechanism since it is not blocked by aminophylline. Thus, its mechanism, which appears distinct from experimental ischemic preconditioning, remains unidentified.

Relationship between Hyperinsulinemia and Ambulatory Blood Pressure Monitoring of Lean and Overweight Male Hypertensives

To elucidate the role of hypertension as part of a state of insulin resistance. Thirty-one uncomplicated hypertensive men not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period and 10 lean normotensive controls were compared. Hypertensive men were divided according to their body mass index into three groups. All subjects came to the clinic for measurements of height, weight, hip and waist circumferences, and sitting blood pressure, and to begin 24 h ambulatory blood pressure monitoring. Plasma glucose and insulin levels were measured during a 2 h oral glucose (75 g)-tolerance test. For the hypertensive population as a whole, behaviors of studied variables among dippers (n = 18) and nondippers (n = 13) were determined. During oral glucose-tolerance testing blood glucose levels after 60 min and 120 min were significantly higher (P < 0.05) in members of the high body mass index group than they were in members of the low body mass index group. Insulin levels of members of the high and middle body mass index groups were higher than those of members of the low body mass index group after 60 min (P < 0.05 for both comparisons) and 120 min (P < 0.05 for both comparisons). The mean serum insulin level in members of the low body mass index group was significantly higher than that in normotensives after 30 min, 60 min and 120 min (P < 0.05 for all three comparisons). The mean serum insulin: plasma glucose ratio for men in the low BMI group was significantly higher than that for normotensives after 60 min and 120 min (P < 0.05 for both comparisons). Correlations of blood pressure and insulin levels were not significant. Levels of high-density lipoprotein cholesterol and triglycerides were lower in members of the group with high body mass index than they were in members of the group with low body mass index. Total cholesterol: high-density lipoprotein cholesterol ratio was higher for members of the high body mass index group than it was for members of the middle body mass index group. Weight, body mass index, casual systolic blood pressure, 24 h average systolic blood pressure and diastolic blood pressure, 0700-2300 h systolic blood pressure, and 24 h average heart rate-systolic blood pressure product of dippers were significantly lower than those of nondippers. These results suggest that hypertension and being overweight have additive effects increasing insulinemia and that being overweight is associated with a significantly lower nocturnal fall in blood pressure.

Effects of intravenous theophylline on exercise-induced myocardial ischemia: II. A concentration-dependent phenomenon

Objectives. The effects of varying concentrations of theophylline on exercise-induced myocardial ischemia were evaluated in patients with stable coronary artery disease.Background. Theophylline is a competitive antagonist of adenosine and may have potential as an anti-ischemic medication. It is not known whether these effects on myocardial ischemia are concentration dependent.Methods. In a double-blind, randomized, crossover manner, 11 patients received, at 1-week intervals, placebo and each of three theophylline doses by intravenous infusion for 45 min. Graded exercise testing was performed before randomization and immediately after each infusion. Concurrent anti-ischemic medications were withheld for 24 h before each exercise test. Serum theophylline concentrations achieved were 3.9 ± 1.0 mg/liter (low), 8.2 ± 1.8 mg/liter (medium) and 13.2 ± 2.3 mg/liter (high).Results. Compared with placebo, none of the three theophylline infusions produced a significant alteration in rest heart rate, blood pressure, mean frequency or severity of ventricular ectopic activity or noncardiac symptoms. The time to onset of ischemia was progressively increased, with medium and high concentrations achieving statistical significance. Similar patterns were observed for oxygen uptake and the heart rate-systolic blood pressure product at the onset of ischemia. Total exercise duration was significantly prolonged with the medium and high concentrations.Conclusions. It is concluded that administration of varying doses of theophylline before exercise produces a clinically significant and concentration-dependent improvement in the indicators of myocardial ischemia in patients with chronic stable coronary artery disease.

The Threshold for Myocardial Ischemia Varies in Patients with Coronary Artery Disease Depending on the Exercise Protocol

It is generally accepted that angina pectoris and, presumably, myocardial ischemia occur at a fixed heart rate-systolic blood pressure product in a given patient. This concept of a fixed threshold has recently been challenged. To evaluate the effects of varying exercise intensity on the ischemic threshold, 33 patients with coronary artery disease and provokable myocardial ischemia, documented by thallium-201 myocardial perfusion imaging, underwent two exercise tests 2 to 7 days apart. A symptom-limited incremental treadmill exercise test was followed by a 20 min submaximal treadmill test at an intensity approximating 70% of the peak heart rate attained during the incremental test. During the incremental exercise test, angina pectoris developed in 16 patients and 17 patients were asymptomatic. At least 0.1 mV of ST segment depression developed in all subjects during the incremental exercise test at a mean exercise duration of 5.3 ± 2.6 min, a rate-pressure product of 19,130 ± 5,735 and oxygen uptake of 19.6 ± 7.0 ml/kg per min. During the submaximal exercise test, 28 (85%) of the 33 patients had significant ST segment depression. Of these patients, 24 (86%) were asymptomatic, including 10 patients who had previously reported anginal symptoms during the incremental test. The average time to onset of 0.1 mV ST segment depression during the submaximal test was 8.1 ± 4.5 min. These changes occurred at a rate-pressure product of 15,250 ± 3,705 and an oxygen uptake of 14.3 ± 5.9 ml/kg per min, and were significantly (p These results demonstrate that myocardial ischemia, whether or not accompanied by angina pectoris, can occur at a lower rate-pressure product and oxygen uptake during submaximal, steady state exercise compared with symptom-limited incremental exercise. It may be concluded that the ischemic threshold varies under different exercise conditions.

The threshold for myocardial ischemia varies in patients with coronary artery disease depending on the exercise protocol

It is generally accepted that angina pectoris and, presumably, myocardial ischemia occur at a fixed heart rate-systolic blood pressure product in a given patient. This concept of a fixed threshold has recently been challenged. To evaluate the effects of varying exercise intensity on the ischemic threshold, 33 patients with coronary artery disease and provokable myocardial ischemia, documented by thallium-201 myocardial perfusion imaging, underwent two exercise tests 2 to 7 days apart. A symptom-limited incremental treadmill exercise test was followed by a 20 min submaximal treadmill test at an intensity approximating 70% of the peak heart rate attained during the incremental test. During the incremental exercise test, angina pectoris developed in 16 patients and 17 patients were asymptomatic. At least 0.1 mV of ST segment depression developed in all subjects during the incremental exercise test at a mean exercise duration of 5.3 +/- 2.6 min, a rate-pressure product of 19,130 +/- 5,735 and oxygen uptake of 19.6 +/- 7.0 ml/kg per min. During the submaximal exercise test, 28 (85%) of the 33 patients had significant ST segment depression. Of these patients, 24 (86%) were asymptomatic, including 10 patients who had previously reported anginal symptoms during the incremental test. The average time to onset of 0.1 mV ST segment depression during the submaximal test was 8.1 +/- 4.5 min. These changes occurred at a rate-pressure product of 15,250 +/- 3,705 and an oxygen uptake of 14.3 +/- 5.9 ml/kg per min, and were significantly (p less than 0.001) lower than values observed during the graded exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Latissimus Dorsi Cardiomyoplasty in Severe Congestive Heart Failure: The Lyon Experience

Eleven male patients, New York Heart Association (NYHA) Class III, have undergone cardiomyoplasty (Chachques and Carpentier technique). There were no deaths. Two patients suffered from low cardiac output, one patient suffered a massive aortic bifurcation embolism, and one patient had a Legionella pneumonia. All patients recovered well. The follow-up was 6.9 +/- 2.3 months. One patient had a Cardiomyostimulator Pulse Train Generator failure and had it replaced. The first seven patients were evaluated 6 months after surgery. They all improved (Class II) except for one, who was transplanted. The maximal level of exercise was improved (92 +/- 18 W vs 60 +/- 24 W), as was the heart rate-systolic blood pressure product (30,262 +/- 3,119 vs 19,908 +/- 4,190), mainly due to an increase in systolic blood pressure (200.0 +/- 25.5 vs 141.5 +/- 20.3 mmHg). Echographic parameters, maximal oxygen consumption, left ventricular ejection fraction (LVEF), cardiac index, oxygen arteriovenous difference, and cardiac filling pressures did not change. The left ventricular (LV) angiography always showed good contraction of the latissimus dorsi. A problem needing investigation is the principle of cardiomyoplasty (CMP) itself, as the muscle acts more as a lift than as pincers. Our patients, and patients from other series, improved functionally, and they exercised more. Improvement in survival can be studied only by a randomized clinical trial.

Long-term variability of angina pectoris and electrocardiographic signs of ischemia in syndrome X

The long-term course of angina and the electrocardiographic signs of ischemia were assessed in 13 patients (10 women and 3 men, mean age 49 ± 6 years) with typical angina pectoris, positive exercise tests, no evidence of coronary spasm and angiographically normal coronary arteries (syndrome X). Clinical and electrocardiographic parameters as well as results of exercise testing and 24-hour electrocardiographic monitoring were assessed at presentation and after a mean follow-up of 6.3 years (range 3 to 9). Mean number of anginal episodes and nitroglycerin consumption per week were similar at presentation and at the last follow-up. Furthermore, no significant difference was noted in heart rate-systolic blood pressure product at 0.1 mV of ST-segment depression (20,363 ± 5,747 vs 21,649 ± 5,687 beats/min × mm Hg), at angina (19,223 ± 5,680 vs 20,126 ± 6,023 beats/min × mm Hg) and at peak exercise (22,057 ± 5,669 vs 22,868 ± 6,122 beats/min × mm Hg). Time to 0.1 mV of ST-segment depression, to angina and to peak exercise was also similar (595 ± 163 vs 631 ± 184 s, 524 ± 156 vs 571 ± 168 s and 671 ± 168 vs 718 ± 186 s, respectively). The number of episodes of ST-segment depression ≥0.1 mV during etectrocardiographic monitoring was similar at presentation and follow-up (31 vs 25) as was the proportion of painful episodes (39 vs 36%). None of the patients developed major coronary events or cardiomyopathy during follow-up. Thus, although patients with syndrome X seem to have a benign prognosis, angina and electrocardiographic signs of ischemia tend to persist almost unchanged during long periods, adversely affecting lifestyle in a sizable proportion of patients.

Usefulness of myocardial ischemia as predictor of training effect in cardiac rehabilitation after acute myocardial infarction or coronary artery bypass grafting

Exercise capacity increases to a variable degree in coronary patients during cardiac rehabilitation. The effect of baseline exercise-induced ischemia on the response to a 12-week conditioning program was evaluated in 106 coronary patients. The magnitude of exercise conditioning response was greater in nonischemic patients than in ischemic patients, with maximal exercise intensity increasing 69 versus 50% (7.2 to 12.1 vs 7.1 to 10.6 METs) (p < 0.05) and maximal oxygen consumption increasing 28 versus 10% (23.1 to 29.6 vs 23.0 to 25.4 cc/kg/min) (p < 0.05). Markers of conditioning during submaximal exercise such as heart rate and heart rate-systolic blood pressure product were similarly reduced in both groups. The groups did not differ by age, diagnosis, resting ejection fraction, incidence of β-blocker use, maximal exercise capacity, maximal exercise heart rate, blood pressure or intensity of actual exercise training. These results suggest that exercise-induced ischemia alters the stimulus to adapt to exercise training.

Nadolol versus diltiazem and combination for preventing exercise-induced ischemia in severe angina pectoris

Combination β-blocker and calcium antagonist therapy has been shown to be superior to monotherapy with either class of drugs in the treatment of patients with severe angina pectoris. Some combinations of these agents have resulted in an increased frequency of adverse effects. Although nadolol and diltiazem have low incidences of side effects as monotherapy, little is known about their combination. Thus, 18 patients with angina pectoris despite medical therapy were randomly assigned to 3-week periods of nadolol (160 mg/day), diltiazem (240 mg/day) or their combination. At the end of each treatment period, treadmill exercise testing and rest and peak bicycle exercise 2-dimensional echocardiography were performed. The heart rate-systolic blood pressure product was decreased most at peak treadmill exercise with the combination therapy versus monotherapy with either nadolol or diltiazem (12 vs 14 vs 22 × 10 3, respectively, p < 0.05). Exercise duration did not differ with any of the 3 regimens, but the number of patients without angina during exercise was lowest with the combination therapy versus nadolol or diltiazem alone (5, 10 and 11, respectively, p < 0.05); similar results were noted with the number of patients developing 1-mm ST depression on the exercise electrocardiogram (6, 10 and 13, respectively, p < 0.05). The left ventricular ejection fraction at rest and during peak exercise was similar among the 3 treatments. The therapeutic combination of nadolol and diltiazem is well tolerated and results in less evidence of myocardial ischemia during exercise than monotherapy with either agent.

Abolition of holter monitor-detected silent myocardial ischemia after percutaneous transluminal coronary angioplasty

Twenty-four hour Holter ambulatory electrocardiographic recordings were obtained before and after successful coronary angioplasty in 36 patients. Twenty-five patients had one vessel, 10 had two vessel and 1 had three vessel coronary artery disease. Holter monitor-detected myocardial ischemia, defined as ST segment depression or elevation greater than or equal to 1 mm, was present in 10 patients (28%). These 10 patients had a total of 39 ischemic episodes of 3 to 144 minutes' duration, with a total cumulative duration of 398 minutes. None of the 10 had Holter monitor-detected ischemia after successful angioplasty (p less than 0.01). Treadmill exercise duration increased by 29% after coronary angioplasty (p less than 0.01), and peak exercise heart rate-systolic blood pressure product increased by 27% (p less than 0.01). Thus, Holter monitor-detected myocardial ischemia is a relatively uncommon finding in patients with predominant single vessel coronary artery disease undergoing coronary angioplasty. When such ischemia is present, it is eliminated by successful coronary angioplasty.

Inotropic effect of enoximone in patients with severe heart failure: Demonstration by left ventricular end-systolic pressure-volume analysis

Left ventricular end-systolic pressure-volume analysis was employed to assess the inotropic effect of the phosphodiesterase inhibitor enoximone (formerly MDL-17,043) in nine patients with severe heart failure (New York Heart Association class IV symptoms, mean ejection fraction = 0.22). Left ventricular pressure-volume loops were constructed using high fidelity left ventricular pressure measured with micromanometer-tipped catheters and simultaneous left ventricular volume obtained by gated blood pool imaging. Afterload was reduced with the vasodilator nitroprusside to generate the baseline left ventricular end-systolic pressure-volume relation, a relatively load-independent measure of contractile function. The intravenous administration of enoximone (mean dose 75 mg) shifted the end-systolic pressure-volume point upward and leftward from the baseline pressure-volume relation in eight of the nine patients, demonstrating a positive inotropic effect of this agent. The maximal rate of left ventricular pressure development (peak positive dP/dt) increased from 1,030 +/- 142 to 1,381 +/- 219 mm Hg/s (p less than 0.01) on enoximone despite a significant decrease in preload (as assessed by left ventricular end-diastolic pressure and volume) and a small, insignificant decrease in mean arterial pressure. Two patients developed angina after enoximone administration; both patients had coronary artery disease and experienced a greater than 30% increase in heart rate-systolic blood pressure product. Thus, enoximone has a significant inotropic effect in patients with severe heart failure. Like other inotropic drugs, it has the potential to increase myocardial oxygen demand and thereby precipitate ischemia.

Coronary and systemic hemodynamic effects of intravenous nisoldipine

Systemic and coronary hemodynamic effects of the new dihydropyridine calcium antagonist nisoldipine were studied over a 30-minute period in 12 patients with angina pectoris. Previously instituted β-blocker therapy was continued. Nisoldipine was administered in an intravenous bolus of 6 μg/kg over 3 minutes. Heart rate increased as mean aortic pressure and systemic vascular resistance decreased in all patients. Cardiac output increased significantly, from 5.8 ± 0.3 to 7.9 ± 0.5 liters/min, 10 minutes after nisoldipine infusion. These trends were maintained over the 30-minute observation period. Coronary sinus blood flow increased from 103 ± 11 to 139 ± 13 ml/min immediately after nisoldipine, but had returned to the control level by 30 minutes, as had the reduction in coronary vascular resistance. Myocardial oxygen consumption and heart rate-systolic blood pressure product did not change significantly. Nisoldipine is a potent peripheral and coronary vasodilator free of major myocardial depressant effects after acute intravenous administration. The systemic vasodilatory effects appear to outlast the coronary effects over 30 minutes.

Coronary and systemic hemodynamic effects of nicardipine

Systemic and coronary hemodynamic effects of a new dihydropyridine calcium antagonist, nicardipine, were studied in 15 patients. Nicardipine was administered as a 2-mg bolus intravenously followed by an infusion titrated to maintain a 10 to 20-mm Hg decrease in systolic pressure. Nicardipine increased both heart rate from 69 ± 3 to 81 ± 3 beats/min and cardiac output from 7.3 ± 0.5 to 9.9 ± 0.5 liters/min (both p < 0.001) as systemic vascular resistance decreased from 1,183 ± 70 to 733 ± 33 dynes s cm −5 (p < 0.001). Left ventricular end-diastolic pressure remained constant, at 14 ± 1 vs 14 ± 1 mm Hg as stroke volume increased from 108 ± 6 to 123 ± 6 ml/m 2 (p < 0.001). Coronary blood flow increased from 102 ± 9 to 147 ± 13 ml/min, while coronary resistance decreased from 1.17 ± 0.1 to 0.7 ± 0.1 mm Hg/ml/min (both p < 0.001). Heart rate-systolic blood pressure product did not change (104 ± 5 vs 106 ± 5 beats/min mm Hg × 10 −2, difference not significant) with drug administration. At the same heart rate before and during nicardipine administration (using atrial pacing in 6 patients), significant augmentation of coronary flow was still observed. Thirteen of 14 patients showed a greater percent decrease in coronary resistance than systemic vascular resistance. Nicardipine differs from other calcium antagonists with respect to consistent augmentation of coronary blood flow. This effect appears to be the result, in part, of increased potency in the coronary bed compared with the systemic vascular bed.