Regional Left Ventricular Wall Motion Abnormalities in Idiopathic Dilated Cardiomyopathy Katharina Stibrant Sunnerhagen, MD, Valmik Bhargava, PhD, and Ralph Shabetai, MD
An evaluation and a comparison of left ventricular regional wall motion were performed in 32 patients with idiopathic dilated cardiomyopathy, none of whom had coronary artery diameter stenosis exceeding 26% in any major artery, and 17 control subjects, using frame by frame vldeo intensity analysis of digitized ventticulograms. This technique evaluates thei whoie cardiac cycle in short overlapping intervals and yields information for systolii and diastdic events, without assumptions regarding the positkn and orientation of the ventricle. Dtastdic regional wall motion abnormalities were found In 31 of 32 patients and systdic abnormalities were present in 16 patients. Asynchronous regions most commonly detected during diastole were anteroapical and apSeal; they were found in 19 of 32 patients. Regional contraction abnormality was observed in the apical and the anteroapical regions in 6 of 16 patients. Dilatation-induced changes in left ventricular shape exaggerate the phenomenon of higher wall stress at the apex of the normal ventricle. Basal wall motion is thus relatively preserved in dilated cardiomyopathy. (Am J Cardid lBB6;65:364-370)
ystolic and diastolic wall stresses are not uniform throughout the left ventricular myocardium. Thus, although cardiomyopathy is usually a glob al affection of the myocardium,1,2 regional wall motion abnormalities in addition to global hypokinesis may be anticipated.3 This study exploits digital angiography to provide a more detailed picture of regional contraction and relaxation patterns in idiopathic dilated cardiomyopathy. Most earlier angiographic studies of ventricular contraction used 2-frame analysis of the left ventriculogram. Using 1 such method, Leighton et al4 found regional hypokinesia in 3 of 6 patients with cardiomyopathy of unknown type. Other investigators5,6 used frame by frame analysis throughout systole to gain a more complete picture of the extent and timing of regional shortening of the left ventricle. Kreulen et al5 identified 2 groups with unclassified myocardial disease, 1 with only global hypokinesia and 1 with additional regional abnormalities. In another study the same investigator@ showed regional wall motion abnormalities in 3 patients with idiopathic dilated cardiomyopathy. Conventional contrast ventriculographic techniques are limited by the need for a coordinate system. Internal reference systems require assumptions to correct for realignment. If these assumptions are not correct, they would render the technique less reliable.’ Dilatation of the ventricle obscures the location of the apex and makes corrections for realignment even less valid. This is a consideration of great importance in the study of dilated cardiomyopathy. We have developed a video intensity technique for regional wall mbtion analysis that does not require geometric assumptions regarding the shape and position of the heart and is independent of a coordinate system.8,9 This method uses an external reference system, and no correction is made for rotation or translation of the heart.
S
METHODS Patlent population:
From the University of California, San Diego, California, and the Veterans Administration Medical Center, San Diego. Manuscript received August 7, 1989; revised manuscript received October 6, 1989, and accepted October 10. Address for reprints: Valmik Bhargava, PhD, Cardiology (111 A), Veterans Administration Medical Center, 3350 La Jolla Village Drive, San Diego, California 92 161.
364
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
65
The patient population comprised 32 patients with idiopathic dilated cardiomyopathy (Table I). None had a coronary stenosis (measured diameter) exceeding 20% in any major vessel or history of myocardial infarction. The control population consisted of 17 patients, referred for evaluation of chest pain, in whom the coronary angiogram, cardiac struo ture and function proved normal. Fick cardiac output was calculated,‘0 except in 4 cases where thermodilution technique was used. When clinically indicated, endomyocardial biopsies were obtained from the right side of the ventricular septum.
TABLE I Physiologic
Characteristics
and Mode
of Left Ventriculography
in the 32 Patients
Age (yrs), Sex
Angio
BP
ECG
EF
Cl
HR
EDP
AV02
1 2 3 4 5 6
37, 65, 56, 55. 30, 53,
M M M M M M
DLV DLV Levo DLV Levo DLV
loo/75 125/75 90/70 120/64 110/70 120/85
VBG LA, LV AF SR. LV LV
54 15 25 19 32 27
3.1 2.5 2.2 2.2 2.8 1.3
60 120 a4 60 75 71
4 38 8 40
4.2 5.2 5.7
7 8 9 10 11
49, 63, 57, 26, 42.
M M M M M
DLV DLV Levo DLV Levo
148/100 110/70 156/82 KG/70 90/65
SR AF LV AF SR
26 35 47 34 23
2.0 2.4 2.7 2.4 2.4
92 95 84 81 90
36 20 -
10.1 5.4 -
12 13 14 15 16
68, 38, 59, 58, 59,
M F M M M
DLV DLV DLV Levo DLV
160/100 78/55 135/80 110/60 98/68
LV LBBB AF AV, LA, LV
28 15 34 42 18
2.4 3.2 2.8 2.3 2.2
63 115 126 50 93
12 25 12 6 30
5.4 4.1 -
17 18
58, F 29, M
Levo Levo
162/90 110/85*
AF
36 25
2.8 -
63 120
18 -
-
Levo Levo DLV DLV DLV DLV DLV DLV DLV DLV DLV DLV DLV DLV
160/75 130/100 150/70 lOOpI 130/90 90/70 aO/55 86/60 -,98/65 114/100 lCO/6O 100/70 130/90
SR.PQT AF AF LBBB, PQT AF SR SR RBBB PQT SR LV AF, LV
40 26 30 36 38 27 29 35 28 24 28 24 26 29
1.9 2.0 2.1 2.9 2.3 2.2 3.2 2.9 1.6 1.8 2.0 1.8 1.4
66 90 80 a4 91 104 67 84 100 97 135 70 97 100
26 10 20 17 24 16 7 27 28 3 16 12
Pt
19 58, 20 43, 21 75, 22 49, 23 61. 24 32, 25 57, 26 50, 27 --,M 28 64, 29 39, 30 54, 31 70, 32 58, * cuff pressure.
M M F M M M F M M F M M M
6.4
4.8 5.8
6.9 6.0 4.7 5.6 5.9 4.0 5.4 8.3 7.3 6.0 7.3 7.5
with Dilated
Cardiomyopathy
Remarks Hypertrophy, fibrosis Hypertension, ethanol abuse Ethanol abuse Hypertrophy Hypertension, ethanol abuse, diabetes, sarcoidosis Fibrosis Hypertension, degenerative changes Ethanol abuse, hypertrophy, fibrosis Hypertrophy. fibrosis Eosinophilia Ethanol abuse Ethanol abuse Ethanol abuse, hypertrophy, fibrosis Hypertension Hypertension, drug abuse, normal biopsy Ethanol abuse, hypertrophy Normal biopsy Fibrosis Ethanol abuse Ethanol abuse Hypertrophy Hypertrophy Normal biopsy Ethanol abuse Ethanol abuse, normal biopsy Normal biopsy Ethanol abuse, degenerative changes
AF = atrial fibrillabon; AV = firstdegree atrioventricular block: AVO? = artenal venous oxygen saturation difference (volume %); BP = arterial blood pressure (mm Hg); Cl = cardiac index (liters/min/m*); DLV = direct ventriculogram; ECG = electrocardiogram; EDP = left ventricular end-diastoltc pressure (mm Hg); EF = ejecbon fraction (0~); HR = heart rate (beats/min): LA = left atrial hypertrophy; LAD = left axis deviation; LEE% = left bundle branch block; LD = both DLV and Levo: Levo = intravenous contrast injection; LV = left ventricular hypertrophy; PQT = prolonged Q T interval; RBBB = right bundle branch block; SR = sinus rythm: WPW = Woiff-ParkwwxvWhite syndrome; - = not available
Twenty-seven of the 32 patients had a long course of unexplained heart failure and were referred for cardiac catherization for definitive diagnosis, or because of worsening symptoms. The remaining 5 presented clinically with acute cardiac failure and underwent catheterization, coronary angiography and subsequent endomyocardial biopsy to exclude myocarditis and were thereafter diagnosed as dilated cardiomyopathy. Endomyocardial biopsies were performed on 18 patients. Lefl ventriculography: Contrast agent was injected at 12 to 15 ml/s for 3 seconds for direct left ventriculograms, or 25 ml/s for 1.5 seconds was injected in the inferior vena cava for levophase opacification of the left ventricle. Single plane images were acquired in the 30’ right anterior oblique projection. Left ventriculograms from 35 mm tine at 60 frames/s, or from video at 30 frames/s were recorded on a 3/4 inch U-matic tape recorder, using a standard interlaced scanning mode. The second or third well-opacified sinus beat was analyzed. Premature ventricular beats and the succeeding 2 beats were not used. For analysis of levophase images, the best opacified sinus beat was analyzed. Levophase images were recorded under fluoroscopy using a manually
selected constant technique (70 to 75 kVP and 2 to 5 Data aequisitionr The video images were digitized at a resolution of 5 12 X 5 12 X 8 bits using a Gould DeAnza video processing system, which was interfaced to a VAX 1 l/750 computer system. Video images acquired over 3 to 10 seconds were digitized and stored on a high speed Winchester disk drive (Figure l), from which the beat for analysis was selected. X-ray images from film were digitized using a General Electric tine projector equipped with a video camera. Fifty consecutive frames (starting with end-diastole) were digitized. Preprocessing of images: The screen was divided into 4 quadrants each 256 X 256 pixels large. We displayed the original image in the upper left quadrant, time-intensity curve in the upper right and 2 processed images in the 2 lower quadrants (Figure 2). A dilated ventricle may encompass more than 256 X 256 pixels. When this occurred, we used pixel averaging (9 studies) or divided the frame into 2 fields and then averaged the pixels (7 studies). Regional wall motion tedmique: The detailed method has been published previously.sq9 Briefly, a region of
THE AMERICAN
JOURNAL
OF CARDIOLOGY
FEBRUARY
1. 1990
365
interest is defined to include the end-diastolic and end- gions represent contraction or relaxation abnormalities. We defined synchronous wall motion as the absence of systolic ventricular shells. The average time-intensity curve for this region is computed for the entire cardiac any such region occupying >2% of the ventricular area. The duration of abnormality was calculated as (n cycle. For each 100 ms the intensity for a given pixel in the region of interest is correlated with the average in- 1) X (frame time) + 100 ms, where n is the consecutive tensity for the whole ventricle to yield values for the number of images with abnormality. For descriptive purposes, we divided the ventricular slope and correlation coefficient of this relation. Two functional images, slope and correlation coefficient, are image into 6 regions as shown in Figure 5. Statistical analysis: The data were analyzed using created by inserting for each 100 ms intervals in each pixel location the calculated slope or correlation coeffi- the chi-square test. l1 Significance was defined as p cient values. An image sequence is created for the whole l ventricular shell with negative or positive slopes l and thus by definition were within the normal range, these values were slightly lower than for the rest of the ventricle. This indicates that in the normal heart, wall motion in the region of the apex is less than in other regions of the left ventricle. PATIENT GROUP: Diastolic regional wall motion abnormalities were the most common. In 31 of 32 patients early diastolic relaxation abnormalities were detected (p
An evaluation and a comparison of left ventricular regional wall motion were performed in 32 patients with idiopathic dilated cardiomyopathy, none of whom had coronary artery diameter stenosis exceeding 26% in any major artery, and 17 control subjects, using frame by frame vldeo intensity analysis of digitized ventticulograms. This technique evaluates thei whoie cardiac cycle in short overlapping intervals and yields information for systolii and diastdic events, without assumptions regarding the positkn and orientation of the ventricle. Dtastdic regional wall motion abnormalities were found In 31 of 32 patients and systdic abnormalities were present in 16 patients. Asynchronous regions most commonly detected during diastole were anteroapical and apSeal; they were found in 19 of 32 patients. Regional contraction abnormality was observed in the apical and the anteroapical regions in 6 of 16 patients. Dilatation-induced changes in left ventricular shape exaggerate the phenomenon of higher wall stress at the apex of the normal ventricle. Basal wall motion is thus relatively preserved in dilated cardiomyopathy. (Am J Cardid lBB6;65:364-370)
ystolic and diastolic wall stresses are not uniform throughout the left ventricular myocardium. Thus, although cardiomyopathy is usually a glob al affection of the myocardium,1,2 regional wall motion abnormalities in addition to global hypokinesis may be anticipated.3 This study exploits digital angiography to provide a more detailed picture of regional contraction and relaxation patterns in idiopathic dilated cardiomyopathy. Most earlier angiographic studies of ventricular contraction used 2-frame analysis of the left ventriculogram. Using 1 such method, Leighton et al4 found regional hypokinesia in 3 of 6 patients with cardiomyopathy of unknown type. Other investigators5,6 used frame by frame analysis throughout systole to gain a more complete picture of the extent and timing of regional shortening of the left ventricle. Kreulen et al5 identified 2 groups with unclassified myocardial disease, 1 with only global hypokinesia and 1 with additional regional abnormalities. In another study the same investigator@ showed regional wall motion abnormalities in 3 patients with idiopathic dilated cardiomyopathy. Conventional contrast ventriculographic techniques are limited by the need for a coordinate system. Internal reference systems require assumptions to correct for realignment. If these assumptions are not correct, they would render the technique less reliable.’ Dilatation of the ventricle obscures the location of the apex and makes corrections for realignment even less valid. This is a consideration of great importance in the study of dilated cardiomyopathy. We have developed a video intensity technique for regional wall mbtion analysis that does not require geometric assumptions regarding the shape and position of the heart and is independent of a coordinate system.8,9 This method uses an external reference system, and no correction is made for rotation or translation of the heart.
S
METHODS Patlent population:
From the University of California, San Diego, California, and the Veterans Administration Medical Center, San Diego. Manuscript received August 7, 1989; revised manuscript received October 6, 1989, and accepted October 10. Address for reprints: Valmik Bhargava, PhD, Cardiology (111 A), Veterans Administration Medical Center, 3350 La Jolla Village Drive, San Diego, California 92 161.
364
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
65
The patient population comprised 32 patients with idiopathic dilated cardiomyopathy (Table I). None had a coronary stenosis (measured diameter) exceeding 20% in any major vessel or history of myocardial infarction. The control population consisted of 17 patients, referred for evaluation of chest pain, in whom the coronary angiogram, cardiac struo ture and function proved normal. Fick cardiac output was calculated,‘0 except in 4 cases where thermodilution technique was used. When clinically indicated, endomyocardial biopsies were obtained from the right side of the ventricular septum.
TABLE I Physiologic
Characteristics
and Mode
of Left Ventriculography
in the 32 Patients
Age (yrs), Sex
Angio
BP
ECG
EF
Cl
HR
EDP
AV02
1 2 3 4 5 6
37, 65, 56, 55. 30, 53,
M M M M M M
DLV DLV Levo DLV Levo DLV
loo/75 125/75 90/70 120/64 110/70 120/85
VBG LA, LV AF SR. LV LV
54 15 25 19 32 27
3.1 2.5 2.2 2.2 2.8 1.3
60 120 a4 60 75 71
4 38 8 40
4.2 5.2 5.7
7 8 9 10 11
49, 63, 57, 26, 42.
M M M M M
DLV DLV Levo DLV Levo
148/100 110/70 156/82 KG/70 90/65
SR AF LV AF SR
26 35 47 34 23
2.0 2.4 2.7 2.4 2.4
92 95 84 81 90
36 20 -
10.1 5.4 -
12 13 14 15 16
68, 38, 59, 58, 59,
M F M M M
DLV DLV DLV Levo DLV
160/100 78/55 135/80 110/60 98/68
LV LBBB AF AV, LA, LV
28 15 34 42 18
2.4 3.2 2.8 2.3 2.2
63 115 126 50 93
12 25 12 6 30
5.4 4.1 -
17 18
58, F 29, M
Levo Levo
162/90 110/85*
AF
36 25
2.8 -
63 120
18 -
-
Levo Levo DLV DLV DLV DLV DLV DLV DLV DLV DLV DLV DLV DLV
160/75 130/100 150/70 lOOpI 130/90 90/70 aO/55 86/60 -,98/65 114/100 lCO/6O 100/70 130/90
SR.PQT AF AF LBBB, PQT AF SR SR RBBB PQT SR LV AF, LV
40 26 30 36 38 27 29 35 28 24 28 24 26 29
1.9 2.0 2.1 2.9 2.3 2.2 3.2 2.9 1.6 1.8 2.0 1.8 1.4
66 90 80 a4 91 104 67 84 100 97 135 70 97 100
26 10 20 17 24 16 7 27 28 3 16 12
Pt
19 58, 20 43, 21 75, 22 49, 23 61. 24 32, 25 57, 26 50, 27 --,M 28 64, 29 39, 30 54, 31 70, 32 58, * cuff pressure.
M M F M M M F M M F M M M
6.4
4.8 5.8
6.9 6.0 4.7 5.6 5.9 4.0 5.4 8.3 7.3 6.0 7.3 7.5
with Dilated
Cardiomyopathy
Remarks Hypertrophy, fibrosis Hypertension, ethanol abuse Ethanol abuse Hypertrophy Hypertension, ethanol abuse, diabetes, sarcoidosis Fibrosis Hypertension, degenerative changes Ethanol abuse, hypertrophy, fibrosis Hypertrophy. fibrosis Eosinophilia Ethanol abuse Ethanol abuse Ethanol abuse, hypertrophy, fibrosis Hypertension Hypertension, drug abuse, normal biopsy Ethanol abuse, hypertrophy Normal biopsy Fibrosis Ethanol abuse Ethanol abuse Hypertrophy Hypertrophy Normal biopsy Ethanol abuse Ethanol abuse, normal biopsy Normal biopsy Ethanol abuse, degenerative changes
AF = atrial fibrillabon; AV = firstdegree atrioventricular block: AVO? = artenal venous oxygen saturation difference (volume %); BP = arterial blood pressure (mm Hg); Cl = cardiac index (liters/min/m*); DLV = direct ventriculogram; ECG = electrocardiogram; EDP = left ventricular end-diastoltc pressure (mm Hg); EF = ejecbon fraction (0~); HR = heart rate (beats/min): LA = left atrial hypertrophy; LAD = left axis deviation; LEE% = left bundle branch block; LD = both DLV and Levo: Levo = intravenous contrast injection; LV = left ventricular hypertrophy; PQT = prolonged Q T interval; RBBB = right bundle branch block; SR = sinus rythm: WPW = Woiff-ParkwwxvWhite syndrome; - = not available
Twenty-seven of the 32 patients had a long course of unexplained heart failure and were referred for cardiac catherization for definitive diagnosis, or because of worsening symptoms. The remaining 5 presented clinically with acute cardiac failure and underwent catheterization, coronary angiography and subsequent endomyocardial biopsy to exclude myocarditis and were thereafter diagnosed as dilated cardiomyopathy. Endomyocardial biopsies were performed on 18 patients. Lefl ventriculography: Contrast agent was injected at 12 to 15 ml/s for 3 seconds for direct left ventriculograms, or 25 ml/s for 1.5 seconds was injected in the inferior vena cava for levophase opacification of the left ventricle. Single plane images were acquired in the 30’ right anterior oblique projection. Left ventriculograms from 35 mm tine at 60 frames/s, or from video at 30 frames/s were recorded on a 3/4 inch U-matic tape recorder, using a standard interlaced scanning mode. The second or third well-opacified sinus beat was analyzed. Premature ventricular beats and the succeeding 2 beats were not used. For analysis of levophase images, the best opacified sinus beat was analyzed. Levophase images were recorded under fluoroscopy using a manually
selected constant technique (70 to 75 kVP and 2 to 5 Data aequisitionr The video images were digitized at a resolution of 5 12 X 5 12 X 8 bits using a Gould DeAnza video processing system, which was interfaced to a VAX 1 l/750 computer system. Video images acquired over 3 to 10 seconds were digitized and stored on a high speed Winchester disk drive (Figure l), from which the beat for analysis was selected. X-ray images from film were digitized using a General Electric tine projector equipped with a video camera. Fifty consecutive frames (starting with end-diastole) were digitized. Preprocessing of images: The screen was divided into 4 quadrants each 256 X 256 pixels large. We displayed the original image in the upper left quadrant, time-intensity curve in the upper right and 2 processed images in the 2 lower quadrants (Figure 2). A dilated ventricle may encompass more than 256 X 256 pixels. When this occurred, we used pixel averaging (9 studies) or divided the frame into 2 fields and then averaged the pixels (7 studies). Regional wall motion tedmique: The detailed method has been published previously.sq9 Briefly, a region of
THE AMERICAN
JOURNAL
OF CARDIOLOGY
FEBRUARY
1. 1990
365
interest is defined to include the end-diastolic and end- gions represent contraction or relaxation abnormalities. We defined synchronous wall motion as the absence of systolic ventricular shells. The average time-intensity curve for this region is computed for the entire cardiac any such region occupying >2% of the ventricular area. The duration of abnormality was calculated as (n cycle. For each 100 ms the intensity for a given pixel in the region of interest is correlated with the average in- 1) X (frame time) + 100 ms, where n is the consecutive tensity for the whole ventricle to yield values for the number of images with abnormality. For descriptive purposes, we divided the ventricular slope and correlation coefficient of this relation. Two functional images, slope and correlation coefficient, are image into 6 regions as shown in Figure 5. Statistical analysis: The data were analyzed using created by inserting for each 100 ms intervals in each pixel location the calculated slope or correlation coeffi- the chi-square test. l1 Significance was defined as p cient values. An image sequence is created for the whole l ventricular shell with negative or positive slopes l and thus by definition were within the normal range, these values were slightly lower than for the rest of the ventricle. This indicates that in the normal heart, wall motion in the region of the apex is less than in other regions of the left ventricle. PATIENT GROUP: Diastolic regional wall motion abnormalities were the most common. In 31 of 32 patients early diastolic relaxation abnormalities were detected (p
