Sequence and magnitude of ventricular volume changes in painful and painless myocardial ischemia

Stimulation of left ventricular stretch receptors has been proposed as a possible mechanism for the occurrence of cardiac pain. Changes in left ventricular volume were continuously assessed in 12 patients during 11 spontaneous (two painful) and 12 ergometrine-induced (nine painful) ischemic attacks with a precordial scintillation probe and blood pool labeling with technetium-99m. In all ischemic episodes, spontaneous or induced, painful or painless, severe dilatation of the left ventricle was consistently observed. These changes always preceded the onset of ST segment shifts and occurred long before pain, when present. The maximum increase in end-diastolic volume was slightly greater in painful than in painless episodes, 38 +/- 8.0% versus 28 +/- 12.4%, but no significant difference was observed in the rate of volume change or in the maximum increase of end-systolic volume (133 +/- 50% and 110 +/- 27.3%), stroke volume (-28 +/- 15% and -25 +/- 12.4%), or ejection fraction (-32 +/- 8.7% and -26 +/- 6.0%). Although the maximum end-diastolic volume achieved is greater in painful episodes, this effect cannot be separated from that of duration, and, furthermore, there was no significant difference in end-diastolic volume at the moment chest pain began. Thus, in patients with angina at rest, transient asymptomatic ST segment shifts are consistently associated with large changes in left ventricular volume, similar to those observed during painful episodes. The rate and extent of acute left ventricular dilatation do not appear to be factors directly causing anginal pain.     

Current technology in assessing painless and painful ischemia

Recent technologic advances have yielded diverse techniques for studying myocardial ischemia, a useful functional expression of coronary artery disease. These techniques have revealed new characteristics and expanded our understanding of myocardial ischemia. In turn this has led to the establishment of more realistic and discriminating criteria on which to base diagnostic and management decisions. Many of the techniques are noninvasive and can be performed in the cardiologist's office. These include treadmill exercise testing; radioisotope techniques, including ejection fraction studies, stress thallium scintigraphy, and tomographic imaging; and ambulatory monitoring. Other, newer techniques include provocative tests that induce ischemia in patients who cannot exercise. These new noninvasive tests should be used to detect transient ischemia, estimate its severity, and thus record a measure of the patient's risk for adverse coronary events.     

Painless versus painful myocardial ischemia: different left ventricular dysfunction detected by echocardiography

The mechanism responsible for the absence of anginal pain in patients who have episodes of both painless and painful myocardial ischemia, still remains unknown. Does the pain depend on an overstimulation of receptive structures or is this symptom the product of the excitation of a well-defined receptive system? The aim of this work is to test the first hypothesis: whether silent attacks are accompanied by the same degree of mechanical impairment as symptomatic ones. The authors compared the echocardiographic left ventricular functional behavior in the same patient (6 patients) during painful and painless myocardial ischemia. The echocardiographic changes observed during silent ischemic attacks were significantly different from those detected during symptomatic attacks. The latter were characterized by a larger extension of the ischemic myocardium and, as a consequence, by a larger functional impairment. Symptomatic and asymptomatic ischemic attacks were recorded echocardiographically in the same patient during repeated attacks on the same day, and were always clearly differentiated by the degree of wall motion abnormalities. The echocardiographic monitoring during the ischemic attack seemed to confirm that the greater functional impairment preceded the onset of pain leading to the occurrence of this symptom. Nevertheless, it was impossible to identify a threshold value above which the ischemic attack will be symptomatic. Our data seem to indicate a close relationship between painful ischemia and a higher degree of ischemic damage. Thus, in patients with predominantly painful myocardial ischemia, the extension and the severity of ischemia could play an important role in determining this symptom.     

Plasma bradykinin and prostaglandin metabolism and exercise testing in patients with silent myocardial ischemia compared with patients with painful myocardial ischemia

Bradykinin, alone or in combination with prostaglandin, is thought to produce pain in patients with coronary heart disease. To elucidate this further, we have investigated and compared serum bradykinin, TXB2 and 6 KPGF1 alpha levels in patients with silent myocardial ischemia (SMI, n = 18), painful myocardial ischemia (PMI, n = 8) and normal subjects (NL, n = 18). In addition, SMI and PMI subjects were given exercise testing and the results then compared. After Holter monitoring for 48 hours, exercise testing was performed. Blood was sampled in the morning between the Holter and exercise regimen. Maximal heart rate, systolic blood pressure and the double products were not significantly different between the SMI and PMI groups. The duration of exercise for the SMI group was 7.08 +/- 2.1 min vs 5.9 +/- 1.9 in the PMI group (p less than 0.10). Plasma bradykinin was 14 +/- 3 pg/ml in the SMI group and 15 +/- 3 in the PMI group (N.S), whereas it was 7 +/- 4 in the NL (p less than 0.05). The TXB2/6KPGF1 alpha for the SMI group was 1.3 +/- 0.3, which was significantly higher than that for the NL group (0.8 +/- 0.3, p less than 0.01), though this did not greatly differ from the PMI group (1.2 +/- 0.3). These results suggest that SMI patients under Holter monitoring who manifest no symptoms but show significant ST segment depressions must receive the same careful attention given to PMI patients. In both group of patients bradykinin and prostaglandin metabolism is similarly changed, as was demonstrated by exercise stress testing.     

The Nifedipine-Total Ischemia Awareness Program: a national survey of painful and painless myocardial ischemia including results of antiischemic therapy

The Nifedipine-Total Ischemia Awareness Program was designed to evaluate the prevalence, prognostic implications and effect of therapy on painful and painless myocardial ischemic episodes in a nationwide study of patients with angina pectoris. Three hundred forty-eight patients with at least 2 anginal attacks/week while taking antianginal medications were enrolled at 53 participating centers between September 1, 1986 and March 31, 1988; 312 of the 348 patients formed the study group, while 36 patients formed the control group. At least 1 episode of ST-segment depression during two 48-hour periods of Holter monitoring was present in 136 of the 312 patients in the study group. In these 136 patients, there was a total of 372 episodes of ST-segment depression, of which only 69 (18%) were painful; 85% of the 136 patients had either painless episodes only or both painless and painful episodes. Despite apparently adequate antianginal therapy, 48 patients had greater than or equal to 3 episodes of ST-segment depression/48 hours of ambulatory electrocardiographic monitoring, and 38 patients greater than 60 minutes of ST-segment depression. After nifedipine was administered, there was a 23% reduction in the mean number of episodes of ST-segment depression (2.7 +/- 0.3 to 2.1 +/- 0.2, p less than 0.01). The most pronounced effects were found in the 48 patients with greater than or equal to 3 episodes of ST-segment depression and the 38 patients with greater than or equal to 60 minutes of total ischemic time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pre-infarction angina elicits greater myocardial viability on reperfusion after myocardial infarction: a dobutamine stress echocardiographic study

OBJECTIVES: We sought to evaluate myocardial viability (inotropic reserve) after myocardial infarction (MI) and its relationship with the presence of unstable pre-infarction angina (PIA). BACKGROUND: Several studies have suggested that PIA can limit infarct size, but it is not known whether PIA can elicit myocardial viability after an acute MI, with left ventricular function improvement. METHODS: Before discharge from the hospital, 91 patients with a reperfused MI (either fibrinolysis or primary coronary angioplasty) had low-dose dobutamine echocardiography performed to assess the myocardial inotropic reserve of the infarct-related area. RESULTS: Twenty-nine patients (31.9%) had PIA in the 24-h period before the onset of MI. Nine patients were treated with primary coronary angioplasty: five (8.1%) in the group with PIA and four (13.8%) in the group without PIA. There were no other significant differences in the baseline characteristics of the patients. There were more viable segments in patients with PIA (44.9% vs. 30.7%, p = 0.007), and the number of patients with significant viability was higher in the PIA group (73.9% vs. 46.3%, p = 0.026). This occurred despite a similar number of segments with segmental wall abnormalities at baseline in both groups (46.1% vs. 46.9%, p = NS). CONCLUSIONS: The presence of previous unstable PIA induces greater myocardial viability of the infarct-related area upon reperfusion and, as such, could have considerable therapeutic and clinical implications.     

Cardiopulmonary exercise testing is more accurate than ECG-stress testing in diagnosing myocardial ischemia in subjects with chest pain

Background

Cardiopulmonary exercise stress testing (CPET) is used to grade the severity of heart failure and to assess its prognosis. However it is unknown whether CPET may improve diagnostic accuracy of standard ECG stress testing to identify or exclude obstructive coronary artery disease (O-CAD) in patients with chest pain.

Methods

We prospectively studied 1265 consecutive subjects (55 ± 8 years, 156 women) who were evaluated with ECG stress testing (ET) for chest pain. No one had a documented O-CAD. All patients performed an incremental CPET with ECG recordings on an electronically braked cycle ergometer.

Results

Of 1265 patients, 73 had a positive CPET and 1192 had a negative CPET. Seventy-three patients with a positive CPET and 71 patients with a negative CPET agreed to undergo nuclear SPECT imaging and coronary angiography. Follow-up lasted 48 ± 7 months. As compared with ET, sensitivity, specificity, PPV and NPV were all improved significantly (ET: 48%, 55%, 33%, 95%; CPET: 88%, 98%, 73%, 99%, respectively, P < 0.001). Patients with both peak VO₂ > 91% of predicted VO₂ max and absence of VO₂-related signs of myocardial ischemia had no evidence of O-CAD in 100% of cases. Cardiac events occurred in 32 patients with a positive CPET and 8 patients with a negative CPET (log rank 18.2, P < 0.0001).

Conclusions

In patients with chest pain, CPET showed a better diagnostic and predictive accuracy than traditional ET to detect/exclude myocardial ischemia. Its use should be encouraged among physicians as a first line diagnostic tool in clinical practice.     

Papillary muscle dysfunction in acute myocardial infarct: a clinical and Doppler echocardiographic study

The "papillary muscle dysfunction" concept includes a disrupted sequence of one or more structures of the mitral valve complex and not merely a disturbance of a papillary muscle itself. We studied a group of seventeen patients, 14 men and 3 women (mean age 51 and 39 years, respectively). Acute myocardial infarction was the first evidence of heart disease. In all of them, Doppler and M mode echocardiography were performed and correlation clinical features were done. In addition a tricuspid regurgitation flow patterns was scanned on each patient. Mitral regurgitation was found in 29% of them by Doppler echocardiography and only 17% had a mitral systolic murmur suggestive of this entity. In those patients with mitral regurgitation-flow patterns, the infarct site was similar to those with anterior and inferior infarction and serum CPK-level was greater in these patients than the non-mitral regurgitation flow pattern group. The evidence of tricuspid regurgitation by pulsed-Doppler echocardiography was associated with mitral regurgitation in 80% of patients, mainly those with right ventricular extension of acute myocardial infarction, and with the greatest hemodynamic impairment. It seems likely in this study, that mitral regurgitation was due to valve ring dilation with an increase of left ventricular diameter and a decrease on ventricular systolic function.     

Habitual low-intensity exercise does not protect against myocardial dysfunction after ischemia in rats.

BACKGROUND: It is well established that participation in a chronic exercise program can reduce coronary heart disease (CHD) risk factors and improve myocardial tolerance to ischemia-reperfusion (I-R) injury. Low-intensity exercise programs are known to be effective in reducing CHD risk factors in humans and rats, but whether similar programs are of sufficient intensity to improve intrinsic tolerance to I-R injury has not been established. Thus, the purpose of this study is to determine whether low-intensity exercise provides self-protection to the heart against I-R injury. METHODS: Male, Sprague-Dawley rats were exercised on a treadmill at an intensity of 55-60% VO2max, 40 min/day, 5 days/week for 16 weeks. Reperfusion injury following 20 min of global ischemia was evaluated using the isolated perfused working heart model. Left ventricular content of the cytoprotective protein heat shock protein 70 (HSP70) was determined by Western blotting. RESULTS: The exercise program elevated HSP70 2.7-fold, but did not provide enhanced protection following 20 min of ischemia. Final post-ischemic recovery of cardiac external work was 63+/-9% of pre-ischemic value in the sedentary group (n=9) and 51+/-11% in the exercising group (n=9) (P>0.05). Post-ischemic lactate dehydrogenase release was also similar between groups and the magnitude of release was low, consistent with stunning. CONCLUSIONS: Regular exercise at 55-60% VO2max is below the threshold intensity necessary to induce intrinsic cardioprotection against I-R injury. Furthermore, elevated myocardial HSP70 is not necessarily a marker of improved protection against dysfunction associated with stunning.     

Influence of pacing-induced myocardial ischemia on left atrial regurgitant jet: A transesophageal echocardiographic study

Objectives. We investigated the influence of pacing-induced myocardial ischemia on systolic regurgitant jet in the left atrium, using simultaneous transesophageal echocardiography and transesophageal atrial pacing.Background. In vitro studies have shown that ischemia-induced mitral regurgitation may occur as a result of mitral leaflet malcoaptation or (global) left ventricular dysfunction. However, no transesophageal echocardiographic study has thus far been performed to demonstrate the mechanism and extent of mitral regurgitation during myocardial ischemia in patients.Methods. In 24 patients (mean [±SD] age 57 ± 10 years) with (15 patients) and without (9 control subjects) coronary artery disease, heart rate, blood pressure and systolic regurgitant jet were assessed before and immediately after pacing. Pacing was increased stepwise up to 160 beats/min to provoke wall motion abnormalities while the left ventricular short axis was monitored at the midpapillary muscle level. Other variables obtained before and at peak pacing included left ventricular end-diastolic and end-systolic areas and left ventricular end-diastolic and end-systolic endocardial segmental lengths.Results. Heart rate and blood pressure before and after pacing were not significantly different in control subjects or in patients. At baseline, a jet was present in all but three control subjects. New or increased anterior or posterior wall motion abnormalities were observed during pacing in seven and eight patients, respectively. End-systolic left ventricular areas and segment lengths were significantly reduced in control subjects compared with patients with coronary artery disease at peak pacing (p < 0.05). The increase in systolic regurgitant jet was significantly greater in patients (2.0 ± 1.1 to 3.1 ± 1.8 cm²vs. 0.7 ± 0.7 to 0.9 ± 0.9 cm²[after pacing], p < 0.01). This effect was greater in patients with posterior than with anterior wall motion abnormalities (3.5 ± 1.6 vs. 2.1 ± 1.2 cm²[after pacing], p < 0.05).Conclusions. Quantitative changes in geometry and function of the left ventricle caused by pacing-induced myocardial ischemia augments systolic regurgitant jet size. An increase in the jet during atrial pacing is associated with new or increased wall motion abnormalities, especially of the posterior wall. Pacing-induced anterior wall motion abnormalities appear not to be related directly to an increase in the jet.     

Hyperuricemia and the echocardiographic measures of myocardial dysfunction

Few studies have investigated the association between hyperuricemia and subclinical myocardial dysfunction. The authors analyzed the relationship between serum uric acid and subclinical markers of heart failure in participants in the Framingham Offspring Cohort (N=2169, mean age 57.3 years, 55.4% women). Cardiac dysfunction was assessed through echocardiographic measurements of left ventricular (LV) mass and thickness, end-diastolic LV thickness, and LV fractional shortening at the sixth visit, approximately 24 years after study onset. Participants in the highest serum uric acid quartile (≥ 6.2 mg/dL serum uric acid) had a significantly greater frequency of echocardiographic abnormalities compared with those in the lowest quartile (<4.3 mg/dL). Those in the highest quartile had multivariable-adjusted odds ratios of 9.013 (95% confidence interval, 2.051-39.604) for abnormal LV ejection fraction and 4.584 (95% confidence interval, 1.951-10.768) for LV systolic dysfunction compared with those in the lowest quartile. Hyperuricemia in young adults can be a marker for subsequent heart failure.     

Characteristics of coronary artery lesions in patients with painless myocardial ischemia

AIM: To assess extent and localization of coronary artery lesions in patients with painless myocardial ischemia. MATERIAL AND METHODS: Tredmill stress-echocardiograghy, Holter ECG monitoring and coronary angiography were carried out in 59 male patients (age 30-72, mean 54.5 years) with either angina pectoris or painless ischemia. RESULTS: Among patients with painless ischemia 50% had 2-vessel disease, mostly with right coronary artery involvement (87.5%) and there was no case of left main stenosis. Patients with angina were characterized by significantly higher index of obstruction (p<0.005) and often had multivessel coronary artery disease (48.8%). CONCLUSION: Patients with effort angina compared with those with painless ischemia had more extensive and severe coronary artery involvement while the latter more often had right coronary artery stenoses.     

Transient myocardial ischemia with minimal electrocardiographic changes: an echocardiographic study in patients with Prinzmetal's angina

Kn patients with Prinzmetal's angina, episodes of transient T wave abnormalities (T abn) are often documented in addition to the typical episodes of ST segment elevation (ST). As the interpretation of these minor ECG changes is still uncertain, we investigated if transient T abn are associated with reversible ventricular asynergies, similar to episodes with ST. For this purpose an ECG lead and a two-dimensional echocardiographic projection, which showed clear-cut changes during previous episodes of ST, were simultaneously monitored in five patients with Prinzmetal's angina for a total of 13 hours and 20 minutes. In all patients, the 30 episodes of ST recorded were all accompanied by reversible ventricular asynergies. Furthermore, in four of these patients, 14 episodes of T abn (peaking, flattening, or the appearance of a diphasic T wave) were recorded. All T abn were associated with reversible asynergies, as detected by three independent observers. The mechanical impairment occurred in the same ventricular wall both during ST and during T abn. During T abn the degree of mechanical impairment appeared less severe (hypokinesia in 12 and akinesia in two episodes) than during ST (hypokinesia in one, akinesia in 25, and dyskinesia in four episodes) (p less than 0.001). The duration of asynergies was less during T abn (107 +/- 76 seconds) than during ST (169 +/- 83 seconds) (p less than 0.05). Chest pain was reported in 5 of 14 episodes of T abn (36%) and in 20 of 30 (66%) episodes of ST (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Patients with large myocardial infarction gain a greater improvement in exercise capacity after exercise training than those with small to medium infarction

BACKGROUND: It remains unclear whether patients with large-size myocardial infarction (MI) achieve the same benefit from exercise training as do those with small- to medium-size MI. HYPOTHESIS: This study was designed to determine the magnitude and mechanisms underlying improvement in exercise capacity in patients with large-size MI after cardiac rehabilitation. METHODS: In all, 296 patients who participated in a cardiac rehabilitation program after acute MI were divided into two groups according to the peak serum creatine phosphokinase (CPK) level: the group with large infarction (Group 1) (> or = 5000 U/l peak CPK, 64 patients) and the group with less extensive infarction (Group 2) (< 5000 U/I, 232 patients). Exercise capacity was assessed before and after a 3-month cardiac rehabilitation program that included exercise training. RESULTS: Before exercise training, both the peak work rate (p < 0.05) and peak oxygen uptake (VO2) (p < 0.01) were significantly lower in Group 1 than in Group 2. After exercise training, the changes in peak work rate and peak VO2 were significantly greater in Group 1 than in Group 2 (both p < 0.01). The infarction size measured by the peak CPK level correlated significantly with both the baseline exercise capacity and its improvement after exercise training, although these correlations were insignificant in a multivariate analysis. In the multivariate analysis, the improvement in exercise capacity is determined by age and baseline exercise capacity, which is determined by the duration of inactivity, minute ventilation (VE)/VCO2 slope and left ventricular end-diastolic pressure. CONCLUSIONS: Compared with patients with small- to medium-size myocardial infarction, patients with large infarction gain a greater improvement in exercise capacity after exercise training due to reversal of physical deconditioning and improvement in congestive heart failure.     

Demonstration of exercise-induced painless myocardial ischemia in survivors of out-of-hospital ventricular fibrillation

To ascertain if myocardial ischemia is the mechanism of out-of-hospital ventricular fibrillation (VF), left ventricular (LV) function was assessed at rest and during submaximal exercise in 15 patients who survived out-of-hospital VF. They were separated into asymptomatic (9 patients, group A) and symptomatic (6 patients, group S) groups for a history of angina or myocardial infarction. Both groups had significant (at least 70% diameter stenosis) coronary artery disease. At catheterization no patient had angina during exercise, but 12 of 15 had ST depression or increased ST depression (group A, 1.9 +/- 1.4 mm; group S, 1.1 +/- 1.2 mm) and 11 had abnormal wall motion. From rest to exercise, patients in group S had increased LV end-diastolic pressure (from 21 +/- 9 to 37 +/- 11 mm Hg, p = 0.009) and volume (from 100 +/- 25 to 107 +/- 26 ml/m2, p = 0.006), with no significant change in LV ejection fraction (from 40 +/- 13 to 42 +/- 12%). In group A LV end-diastolic pressure increased from 19 +/- 4 to 31 +/- 8 mm Hg (p = 0.001), but neither end-diastolic volume nor ejection fraction changed significantly (from 83 +/- 13 to 92 +/- 23 ml/m2 and from 55 +/- 13% to 46 +/- 13%, respectively). Thus, patients with coronary artery disease who survive out-of-hospital VF may have evidence of myocardial ischemia during exercise without pain. Painless ischemia may have a role in out-of-hospital VF.     

Manifestations of painless myocardial ischemia in patients with chronic obstructive pulmonary disease

Aim of the study was to investigate prevalence and special characteristics of manifestations of painless myocardial ischemia (PMI) in patients with chronic obstructive pulmonary disease (COPD) at exacerbation stage with various degree of severity and to assess risk of cardiovascular events in this group of patients. We carried out complex clinical-instrumental and laboratory examination of 54 patients with COPD. Examination included 24 hour Holter ECG monitoring, registration of parameters of pulmonary function, and endothelium dependent and independent vasoreactivity, determination of lipid spectrum, blood gases composition. We established that aggravation of degree of COPD severity was associated with increase of frequency of episodes of PMI and their total daily duration. During 12 months follow up incidence of cardiovascular events in the group of patients with episodes of PIM was 66.6%