Identification of patients with coronary artery disease by assessing diastolic abnormalities during isometric exercise.

BACKGROUND: Previous clinical studies using invasive and noninvasive methods have shown handgrip-induced diastolic abnormalities in patients with coronary artery disease (CAD). HYPOTHESIS: The study was undertaken to determine the utility of Doppler echo- and pressocardiography during hand-grip in discriminating patients with coronary artery disease (CAD) and in those with normal coronary arteries. METHODS: Both methods were obtained in 96 patients with suspected CAD within 24 h before coronary angiography. An abnormal handgrip-Doppler was defined by an early (E) to late (A) transmitral flow velocities ratio (E/A) < 1 during handgrip and a positive handgrip pressocardiographic test (HAT) by an abnormal increase in the A wave/total excursion or prolongation of the absolute or relative (heart-rate corrected) total relaxation time during isometric exercise. RESULTS: Of the 96 patients studied, 23 had normal coronary arteries and 73 showed CAD. In patients with normal coronary arteries, handgrip-Doppler showed an abnormal average E/A at rest and during handgrip, whereas all variables of HAT were within normal limits. In patients with CAD, handgrip-Doppler showed only a moderate handgrip-induced increase in average A (+ 19%, p < 0.001), whereas HAT showed a significant (p < 0.001) increase in mean A wave/total excursion (+ 60%) and decrease in the relative total relaxation time (- 17%). Furthermore, handgrip-Doppler and HAT were abnormal in 15 of 23 (65%, specificity 35%) and the HAT in 5 of 23 (22%, specificity 78%) patients with normal coronary arteries, as well as in 57 of 73 (sensitivity 78%) and 69 of 73 (95%) patients with CAD. CONCLUSIONS: Our study demonstrates that these noninvasive stress tests can become a useful new diagnostic modality for detecting patients with unknown or suspected CAD.

Usefulness of noninvasive detection of left ventricular diastolic abnormalities during isometric stress in hypertrophic cardiomyopathy and in athletes.

We showed previously that the handgrip apexcardiographic test (HAT) is a useful method for detecting left ventricular (LV) diastolic abnormalities in patients with coronary artery disease and systemic hypertension. This study evaluates the use of HAT for assessing the prevalence and types of exercise-induced diastolic abnormalities in patients with obstructive (n = 31) and nonobstructive (n = 35) hypertrophic cardiomyopathy (HC) as well as its potential value for separating healthy subjects and athletes from patients with HC. We obtained a HAT in 66 consecutive patients with HC and in 72 controls (52 healthy volunteers and 20 athletes). A positive HAT was defined by the presence of one of the following: (1) relative A wave to total height (A/H) during or after handgrip > 21% (compliance type), (2) total apexcardiographic relaxation time (TART) > 143 ms or the heart rate corrected TART (TARTI) during handgrip < 0.14, (relaxation type), (3) both types present (mixed type), and (4) diastolic amplitude time index (DATI = TARTI/[A/D]) during handgrip < 0.27. Of the controls, only 1 of 52 healthy subjects and 1 of 20 athletes showed a positive HAT, whereas of the total HC cohort 63 of 66 patients (95%) had a positive result. There was no significant difference in the distribution of these types between obstructive and nonobstructive HC. Further, no LV diastolic abnormalities were present in 10 of 35 patients (29%) with nonobstructive HC at rest and in 3 of 35 patients (9%) during handgrip, whereas of the patients with obstructive HC only 1 of 31 (3%) had no LV diastolic abnormalities at rest and none during handgrip. Based on HAT data, our study demonstrates that in HC (1) LV diastolic abnormalities are very frequent during handgrip; (2) patients with nonobstructive HC show significantly fewer LV diastolic abnormalities at rest than those with obstructive HC; and (3) no significant difference exists between obstructive and nonobstructive HC in the prevalence of types of handgrip-induced LV diastolic abnormalities. Consequently, HAT appears to be of clinical value as an additional tool for separating normal patients and athletes from patients with HC.

Patterns of diastolic abnormalities during isometric stress in patients with systemic hypertension.

This study was undertaken to determine the prevalence and distribution of diastolic function abnormalities at rest and during isometric exercise in patients with systemic hypertension using the recently introduced handgrip-apexcardiographic test (HAT). It has been shown that HAT reflects left ventricular pressure changes in early (relaxation) and late (compliance) diastole. A HAT was obtained in 132 patients with systemic hypertension (duration >1 year) without history of congestive heart failure. A healthy group (n = 186) served as control subjects. Diastolic abnormalities were present at rest in 53/132 (40%) and during isometric handgrip stress in 92/132 (70%) patients. At rest the most frequent diastolic abnormality was the prolongation of relaxation time (27%) whereas an isolated increase in A wave was rare (8%). During isometric exercise, however, an elevation of A wave was the predominant abnormality (38%) whereas an isolated prolongation of relaxation time was less frequent (14%). Alternatively, an 'ischemic' pattern (abnormal prolongation of resting normal relaxation time during handgrip and/or abnormal as well as more than double increase of resting normal relative A wave to total height during or after handgrip) was observed in 29%. In 89% of these patients with an ischemic pattern of diastolic changes, a typical angina and/or positive stress ECG and/or angiographically proved coronary artery disease were present. Using HAT data the present study demonstrates for the first time that in patients with systemic hypertension: (1) diastolic abnormalities occur significantly more frequently during isometric stress than at rest, (2) the most frequently observed diastolic abnormality at rest is the relaxation time prolongation whereas during isometric stress the A wave elevation, and (3) patients with an ischemic pattern of exercise-induced diastolic abnormalities show frequently clinical or angiographic evidence of demand ischemia. Thus, HAT can become a useful additional diagnostic tool for detecting latent diastolic dysfunction and myocardial ischemia in this clinical setting.

Ischemic and nonischemic patterns of diastolic abnormalities during isometric handgrip exercise.

This study establishes the clinical value of the recently introduced handgrip-apexcardiographic test (HAT) as an additional tool for distinguishing exercise-induced diastolic abnormalities in coronary artery disease (CAD) patients from those in patients with hypertrophic cardiomyopathy (HCM). This stress test reliably assessing differences in diastolic indices during handgrip between 305 healthy volunteers and 39 patients with CAD without prior infarction as well as 17 patients with HCM showed two different patterns of handgrip-induced pathological changes in these indices. An 'ischemic diastolic response' was empirically defined by the presence of either a handgrip-induced more than doubling of a resting normal relative A wave to total height of the apex-cardiogram (ischemic compliance response) or a pathological prolongation of a resting normal total apexcardiographic relaxation time (ischemic relaxation response); whereas a 'nonischemic diastolic response' was defined by the presence of a positive HAT and by absence of the above-mentioned ischemic criteria. An ischemic pattern of diastolic abnormalities was present in 72% of CAD patients, whereas 94% of HCM patients showed a 'nonischemic' diastolic response. These results confirm that in CAD patients there is a typical response of diastolic apexcardiographic indices to isometric stress and, therefore, this simple stress test could be potentially useful in separating these patients from those with nonischemic myocardial disease states.

"Accurate" noninvasive detection of diastolic dysfunction by current techniques: fact or fancy?

To evaluate clinically left ventricular (LV) diastolic performance has been recognized in recent years to be an important part in cardiac evaluation, since diastolic abnormalities occur early and are sensitive indicators of diseased myocardium as well as determinants of cardiac output. Data on LV diastolic function are noninvasively acquired in recent years in most laboratories from: 1) radionuclide angiography, 2) echocardiography (M-mode and 2D) and 3) Doppler echocardiography. All these widely accepted and used methods for the detection and quantification of diastolic dysfunction are based on the assessment of indices of either rate of ventricular filling or rate of change of LV diameter and wall thickness during diastole.

[Comparison of the hand grip apex cardiography test and stress ECG for detection of patients with coronary heart disease]. / Vergleich von Handgrip-Apexkardiogramm-Test und Belastungs-EKG zur Erfassung von Patienten mit koronarer Herzkrankheit.

It has been recently demonstrated by many authors that diastolic abnormalities of the left ventricle are the earliest mechanical manifestations of myocardial ischemia preceding both the ECG changes and angina pectoris. Recently, we have shown that using a handgrip-apexcardiographic test (HAT), one can accurately assess exercise-induced abnormalities of diastolic function in patients with angina pectoris or silent ischemia. Aim of this study is to compare the clinical value of HAT and stress-ECG in patients with prospectively documented coronary artery disease (CAD). Subject and methods 275 healthy volunteers (208 men) and 52 patients (47 men) with known (18 with prior infarction) or suspected CAD were examined. HAT and stress-ECG were performed within one month before heart catheterization. There were 17 single, 17 double, and 18 triple vessel disease patients, who showed no large dyskinesias and no wall aneurysms on angiography. Apexcardiogram (ACG) was recorded simultaneously with phonocardiogram and ECG before, during and after a low level (40% of maximal voluntary contraction) isometric stress of short duration (two minutes). As indices of diastolic function served the relative A wave to total (A/H) and to diastolic deflection (A/D) as well as the total apexcardiographic relaxation time (TART) from the onset of the aortic component of the second heart sound (A2) to the protodiastolic nadir of ACG and the TART index (TARTI) given by dividing the square root of the duration of diastolic length with TART (TARTI = square root of A2-C/TART, whereas C is the apexcardiographic onset of the systolic upstroke). Furthermore, the combined index of diastolic function DATI (diastolic amplitude time index) was calculated (DATI = TARTI/[A/D]). A pathologic or positive HAT was defined by the presence of at least one of the following recently introduced criteria: 1. A/H during and/or after handgrip > 21%, 2. TART during handgrip > TART at rest > 143 ms and/or TARTI during handgrip < 0.14, or 3. DATI during handgrip < 0.27; these limits representing the largest and lowest individual values in the controls. Complications occurred less often during HAT than during stress-ECG (angina pectoris: 4% and 25%, ventricular extrasystoles 6% and 16%, respectively). Changes of diastolic apexcardiographic indices As evident in Table 1, in the normals there were only slight, although significant, changes of TART, TARTI, DATI and A/D during handgrip; whereas A/H showed no significant changes.(ABSTRACT TRUNCATED AT 400 WORDS)

Noninvasive detection of coronary artery disease by assessing diastolic abnormalities during low isometric exercise.

The handgrip-apexcardiographic test (HAT) is a simple low-level (40% of maximal voluntary handgrip during 2 min) stress test which can detect left ventricular (LV) diastolic abnormalities. To determine whether it contributes to the diagnosis of coronary artery disease (CAD), HAT was obtained in 68 patients--47 with and 21 without angina pectoris--who prospectively underwent coronary arteriography. According to the highest or lowest individual values of diastolic apexcardiographic indices in 255 healthy volunteers, a pathologic or positive HAT was defined by the presence of at least one of the following new criteria: (1) A wave relative to total height of apexcardiogram during and/or after handgrip > 21%, (2) total apexcardiographic relaxation time (TART) during handgrip > TART at rest > 143 ms and/or TART corrected for the duration of diastole (TARTI) during handgrip < 0.14, or (3) diastolic amplitude time index (DATI), given by dividing TARTI and A wave relative to total diastolic amplitude of apex tracing during handgrip < 0.27. HAT was positive in 20 of 21 patients with single-vessel disease (sensitivity 95%), 21 of 24 patients with double-vessel disease (sensitivity 88%), and in 22 of 23 patients with triple-vessel disease (sensitivity 96%). Furthermore, HAT was positive in 20 of 21 (95%) patients without symptoms. Thus, the overall sensitivity of HAT for detecting CAD was 93%. This study is the first to demonstrate the high sensitivity of HAT in identifying patients with CAD with or without symptoms by assessing diastolic apexcardiographic abnormalities during low-level isometric stress. Thus, HAT potentially could become an additional simple diagnostic tool for noninvasive detection of patients with CAD.

Exercise-induced diastolic abnormalities assessed by handgrip-apexcardiographic test in syndrome X.

It has been shown recently that the handgrip-apexcardiographic test (HAT) represents a new mode of stress test, which shows a high sensitivity in identifying coronary patients by assessing exercise-induced ischemic left ventricular diastolic abnormalities. To assess the prevalence of left ventricular diastolic abnormalities and the usefulness of HAT as a diagnostic tool in patients with syndrome X (angina pectoris in the presence of normal coronary arteries), HAT was obtained in 275 clinically normal subjects and in 9 patients who presented with typical chest pain and who were subsequently found to have a positive treadmill ECG test and no coronary artery disease by angiography. As diastolic indices served: the relative A wave to total height (A/H) and to diastolic amplitude (A/D) of the apex tracing, the total apexcardiographic relaxation time (TART), TART corrected for the duration of diastole (TARTI) and the diastolic amplitude time index [DATI = TARTI/(A/D)]. Positivity of HAT was defined by the presence of at least one of the following recently introduced criteria: (1) A/H during or after handgrip > 21%, (2) TART during handgrip > TART at rest > 143 ms or/and TARTI during handgrip < 0.14 or (3) DATI during handgrip < 0.27. At rest, in 6/9 (67%) patients all variables were within normal limits, whereas in 3/9 (33%) patients an abnormal A/H or TARTI was observed. During and after handgrip, however, all patients showed abnormal changes in at least two diastolic variables, DATI and A/H being most frequently abnormal (67 and 56%, respectively). Further, using the above-mentioned positivity criteria, all patients had a positive HAT result.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of simultaneous Doppler echo and apexcardiogram in detecting left ventricular diastolic dysfunction in patients with systemic hypertension.

Patient with systemic hypertension have often abnormalities of left ventricular (LV) diastolic function. Although pulsed Doppler echocardiography (PDE) is at present time the only simple widely used noninvasive method for evaluating such LV diastolic dysfunction, LV apexcardiogram (ACG) reflecting LV pressure curve changes can also be useful for evaluating LV diastolic events. In order to compare the validity of these two methods in assessing LV diastolic dysfunction, PDE and ACG were simultaneously obtained in 29 patients with chronic systemic hypertension and in 61 controls. As diastolic indices of PDE served the peak early (E) and late atrial (A) diastolic transmitral flow velocities, the A/E ratio and the deceleration time; and of the ACG the relative A-wave to total height (A/H), the total relaxation time (TART), the heart rate corrected TART and the combined index DATI (= diastolic amplitude time index). In patients with hypertension, from the PDE only A and A/E ratio were significantly different from the controls, whereas all mentioned ACG indices showed an abnormal mean value. Thus, the less widely used ACG appears to be a more accurate method in the noninvasive evaluation of diastolic mechanical events than the routinely used PDE in patients with chronic hypertension.

Noninvasive evaluation of progression of ischemic heart disease: 5 year follow-up.

Left ventricular (LV) apexcardiogram can be used for the assessment of LV diastolic abnormalities during isometric handgrip stress. In the present study, the clinical value of handgrip-apexcardiographic test (HAT) for identifying patients with new ischemia by the assessment of LV diastolic abnormalities during HG was prospectively investigated. After 5 years follow-up, 9 at entry asymptomatic patients with prior infarction developed a slight effort angina pectoris as a sign of progression of the disease. The data of HAT obtained at entry were compared with those within one month after the onset of angina. As apexcardiographic indices of LV diastolic function the relative A-wave to total height (A/H) and the total apexcardiographic relaxation time (TART) of the apex tracing were used. In 243 controls A/H averaged at rest 10 +/- 4% and TART 107 +/- 9 ms and changed only slightly during and after handgrip stress. Both indices were in patients at rest and during HAT within normal limits at entry. At 5 years, TART was longer (123 +/- 13 ms) and A/H unchanged at rest. During and after handgrip, however, A/H increased significantly (29 +/- 9% and 24 +/- 6%, respectively, p less than 0.01), whereas TART showed no significant change. Furthermore, all patients had an abnormal A-wave response to isometric stress (A/H during or/and after handgrip higher than 21%, which is the largest individual value in the controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Handgrip-apexcardiographic test: a new mode of detecting patients with silent exercise-induced myocardial ischemia.

There are no simple noninvasive stress tests for detecting silent myocardial ischemia by assessing left ventricular (LV) diastolic abnormalities which are known to occur early on the onset of every ischemic episode. It has been proved that the LV apexcardiogram (ACG) reflects the LV pressure curve in early and late diastole and can be recorded during isometric handgrip (HG) exercise. To determine the clinical validity of HG-ACG-Test (HAT) in identifying patients with silent ischemia, 16 patients (8 with prior infarction) with angiographically documented coronary artery disease, positive treadmill electrocardiographic test and without symptoms were examined. According to the largest and lowest individual values in 253 healthy volunteers, the positivity of HAT was defined by the presence of at least one of the criteria: 1) The relative A-wave to total height of ACG during or/and after HG greater than 21%. 2) The total ACG relaxation time (TART) during HG longer than at rest and also longer than 143 ms or/and the heart rate corrected TART during HG less than 0.14, or 3) the combined index of overall diastolic function DATI (= diastolic amplitude time index) during HG less than 0.27. Based on this definition 14/16 (sensitivity: 88%) patients showed a positive test result. It is concluded that, using new definitions of positivity, HAT shows a high sensitivity for detecting patients with proved silent ischemia providing, thus, providing a new simple clinical tool for the identification of these patients.

[Value of the handgrip apex cardiography test for detection of early diastolic ventricular dysfunction in patients with angina pectoris]. / Bedeutung des Handgriff-Apexkardiogramm-Tests für die Erfassung der frühen diastolischen Ventrikeldysfunktion bei Patienten mit Angina pectoris.

Left ventricular (LV) diastolic dysfunction is the earliest manifestation of myocardial ischemia. There are no simple stress tests for detecting ischemia by assessing abnormal changes of early (relaxation) and late (end-diastolic compliance) LV diastolic function. This study attempts to establish the diagnostic accuracy of the handgrip-apexcardiographic test (HAT) for detecting exercise-ischemia-induced diastolic dysfunction. Apex- and phonocardiogram were obtained during a 2-min handgrip (40% of maximal voluntary contraction using a balloon dynamometer). Indices of LV diastolic function were provided by relative A-wave to total height (A/H) of ACG, total apexcardiographic relaxation time (TART), TART corrected for heart rate (TARTI), and diastolic amplitude time index (DATI). HAT was performed in 63 patients with typical stable angina pectoris and 202 healthy volunteers. Positivity of HAT is defined by the presence of at least one of the following new criteria: 1) A/H during or after handgrip greater than 21% (= largest individual value in controls), 2) TART during greater than TART before handgrip greater than 143 ms or TARTI during handgrip less than 0.14 (= lowest individual value in controls), and 3) DATI during handgrip less than 0.27. According to this definition, all controls showed a negative HAT (specificity: 100%). By contrast, HAT was positive in 54 out of the 63 angina patients (sensitivity: 86%). These results demonstrate that HAT is a highly sensitive stress test for identifying patients with angina pectoris by assessing LV diastolic abnormalities. Thus, this quick and simple exercise method represents a new aspect in the clinical evaluation of angina patients for the practicing physician.

Diastolic amplitude time index: a new apexcardiographic index of left ventricular diastolic function in human beings.

Left ventricular apexcardiography was performed in 260 normal subjects and 37 patients undergoing diagnostic cardiac catheterization: 13 without left heart disease (group 1), 18 with congestive cardiomyopathy (group 2) and 6 with idiopathic hypertrophic subaortic stenosis (group 3). In the patients undergoing catheterization the apexcardiogram was recorded simultaneously with left ventricular pressure (tipmanometer) and its first derivative (dP/dt). The following variables were measured in the apex tracing: (1) the time from the onset of the aortic component of the second heart sound (A2) in the phonocardiogram to the nadir of the apexcardiogram, termed total apexcardiographic relaxation time (TART), (2) the time from A2 to the onset of the systolic upstroke (C point) of the apexcardiogram (A2-C), and (3) the ratio of the A wave (A) to the total diastolic amplitude (D) of the apexcardiogram (A/D). The diastolic amplitude time index (DATI) was calculated according to the following formula DATI = (square root A2-C/TART)/(A/D). In the normal subjects the diastolic amplitude time index was 0.82 +/- 0.26 (mean +/- standard deviation). In group 1 this index was within normal limits; in groups 2 and 3 it was decreased (0.23 +/- 0.07 and 0.18 +/- 0.05, respectively). This index showed excellent correlation with specific compliance of the left ventricle (r = +0.90) and close correlations with the maximal rate of decrease of left ventricular pressure (minimal dP/dt) (r = +0.79) as well as the velocity of lengthening of the contractile elements at minimal dP/dt (r = +0.77); less close correlation was obtained with the end-diastolic volume compliance (r = +0.67). These results demonstrate that the diastolic amplitude time index reflects interpatient differences in both relaxation ability and diastolic distensibility of the human left ventricle. Thus, this measurement provides an important new method for noninvasive evaluation of the overall function of the left ventricle during diastole.

Use of apexcardiography to evaluate left ventricular diastolic compliance in human beings.

The relation between various relative amplitude measurements of the left apexcardiogram and internally derived indexes of diastolic compliance of the left ventricle was studied in 29 patients. Simultaneous high fidelity recordings of the left apex tracing and left ventricular pressure were obtained in 11 patients without left ventricular disease (group I) and 18 patients with congestive cardiomyopathy (group II). In 204 normal subjects the ratio of the A wave amplitude to the total diastolic deflection (A/D ratio) of the left apexcardiogram was 31.4 +/- 11.4 (mean +/- standard deviation) percent, the ratio of the A wave amplitude to the total height (A/H ratio) 8.9 +/- 4.3 percent and the D/H ratio 30.4 +/- 14.7 percent. The A/D and A/H ratios were significantly (P less than 0.001 and P less than 0.005) increased in group II (69.2 +/- 12.2 percent and 16.8 +/- 8.2 percent, respectively); they were within normal limits in group I. In contrast, the D/H ratio was within normal limits in both groups of patients. The A/D ratio correlated significantly better with specific compliance (deltaV/deltaP.V) (r = -0.87) than did the A/H ratio (r = -0.53), whereas similar correlations were obtained with end-diastolic volume compliance (dV/dPV) (r = -0.61 and r = - 0.64, respectively). In contrast, the D/H ratio correlated significantly only with end-diastolic distensibility index (dV/dP) (r = -0.52). It is concluded that A wave amplitude/total diastolic deflection (A/D) ratio and, to a lesser degree, the A wave amplitude/total height (A/H) ratio of the left apexcardiogram correspond best to diastolic compliance and are useful noninvasive measurements of this property of the left ventricle.

Comparison between apexcardiographic and angiographic indexes of left ventricular performance in patients with aortic incompetence.

Left ventricular (LV) apexcardiogram (ACG) and its first derivative (dA/dt) was obtained in 104 normal subjects and 34 patients with chronic aortic incompetence (AI). In the patients with AI the ACG was recorded simultaneously with LV pressure (tipmanometer). The systolic upstroke time (SUT), the time to peak dA/dt (t-dA/dt) and the a wave percentage amplitude (a/H) of the ACG was measured. In normal subjects SUT averaged 99 +/- 17 (SD) msec. In 17 patients with AI and normal ejection fraction (EF) (group 1) SUT was within normal limits; in 17 patients with AI and decreased EF (group 2) it was prolonged (142 +/- 19 msec) (P less than 0.001). The SUT was closely correlated with EF (r = 0.85) and less with contractile indexes derived from pressure curves. The indexes t-dA/dt and a/H were not significantly different in groups 1 and 2; they were weakly correlated only with the time to peak rate of LV pressure rise (r = +0.56) and the LV end-diastolic pressure (r = +0.59), respectively. These results demonstrate the superiority of SUT over the other apexcardiographic parameters. The measure provides another means of noninvasive assessment of the LV performance in patients with AI.