Acute right ventricular dilatation: a new helical CT sign of massive pulmonary embolism

Acute right heart failure is a principal cause of circulatory collapse and death in patients with massive pulmonary embolism (PE). The purpose of this study was to investigate if helical computed tomography (CT) could contribute to the assessment of the right ventricle (RV) in those with massive PE. Over an 8-month period 79 helical CT pulmonary angiograms were performed to investigate suspected PE. Emboli were demonstrated in 28 (35%) patients and seven (9%) were considered to have had a major thromboembolic event. The CT scans of all patients were evaluated using parameters derived in the axial plane (maximum minor axis RV and LV dimensions, RV:LV minor axis ratio and RV wall thickness). Acute right ventricular dilatation with an RV:LV ratio> 1.5:1 (range 1.6:1-2.3:1, mean 2:1) was found in all seven patients who had sustained major PE. In the remaining group of 21 with lesser degrees of embolism no patient had an RV:LV ratio > 1.1:1 (range 0.8-1.1, mean 1.0). To our knowledge, this CT sign has not been described before. CONCLUSION: Helical CT can identify acute RV dilatation in addition to making the primary diagnosis in patients with massive PE. This observation may help identify those at greatest risk of a second fatal event and facilitate therapeutic strategy.     

Influence of longer term left ventricular assist device support on valvular regurgitation

The authors previously published data that describe acute alterations in ventricular dimensions and in the severity of mitral and tricuspid regurgitation (MR/TR) after initiation of left ventricular assist device (LVAD) pumping. In the current study, measurements of ventricular size and regurgitant jet area acquired after LVAD implantation are presented. Eight patients had LVAD implanted pending cardiac transplantation (duration of assist 70-279 days; mean, 162 +/- 29 days). Echocardiograms were obtained at the time of LVAD implant and later during LVAD support (mean time for late echo, 95 +/- 32 days post-implant). Comparisons of pre-implant with late post-implant data showed: increased TR jet area (4.8 +/- 1.0 cm2 vs. 8.0 +/- 1.7 cm2 P < 0.05); increased right ventricular (RV) end-systolic dimension (31 +/- 4 vs 40 +/- 5 mm, P < 0.05); and increased RV end-diastolic dimension (35 +/- 4 vs. 45 +/- 5 mm, P < 0.065). Decreased MR jet area and decreased LV dimensions (P < 0.05) also were noted on comparison of pre-implant and late post-implant data. There were no significant differences between any immediate post-implant and late post-implant echocardiographic measurements. No patient had clinical evidence of RV failure. LV mechanical assist causes an acute increase in TR, presumably by volume loading the RV. TR and RV enlargement persisted but did not discernibly worsen on subsequent post-implant echocardiograms. LV dimensions and MR remained less than the pre-implant values on later post-implant determinations.     

Angiotensin-converting enzyme (ACE) inhibitors revert abnormal right ventricular filling in patients with restrictive left ventricular disease

OBJECTIVES: Our aim was to determine mechanisms underlying abnormalities of right ventricular (RV) diastolic function seen in heart failure. BACKGROUND: It is not clear whether these right-sided abnormalities are due to primary RV disease or are secondary to restrictive physiology on the left side of the heart. The latter regresses with angiotensin-converting enzyme inhibition (ACE-I). METHODS: Transthoracic echo-Doppler measurements of left- and right-ventricular function in 17 patients with systolic left ventricular (LV) disease and restrictive filling before and 3 weeks after the institution of ACE-I were compared with those in 21 controls. RESULTS: Before ACE-I, LV filling was restrictive, with isovolumic relaxation time short and transmitral E wave acceleration and deceleration rates increased (p < 0.001). Right ventricular long axis amplitude and rates of change were all reduced (p < 0.001), the onset of transtricuspid Doppler was delayed by 160 ms after the pulmonary second sound versus 40 ms in normals (p < 0.001) and overall RV filling time reduced to 59% of total diastole. Right ventricular relaxation was very incoordinate and peak E wave velocity was reduced. Peak RV to right atrial (RA) pressure drop, estimated from tricuspid regurgitation, was 45+/-6 mm Hg, and peak pulmonary stroke distance was 40% lower than normal (p < 0.001). With ACE-I, LV isovolumic relaxation time lengthened, E wave acceleration and deceleration rates decreased and RV to RA pressure drop fell to 30+/-5 mm Hg (p < 0.001) versus pre-ACE-I. Right ventricular long axis dynamics did not change, but tricuspid flow started 85 ms earlier to occupy 85% of total diastole; E wave amplitude increased but acceleration and deceleration rates were unaltered. Values of long axis systolic and diastolic measurements did not change. Peak pulmonary artery velocity increased (p < 0.01). CONCLUSIONS: Abnormalities of RV filling in patients with heart failure normalize with ACE-I as restrictive filling regresses on the left. This was not due to altered right ventricular relaxation or to a fall in pulmonary artery pressure or tricuspid pressure gradient, but appears to reflect direct ventricular interaction during early diastole.     

Three-dimensional left ventricular deformation in hypertrophic cardiomyopathy

BACKGROUND: In hypertrophic cardiomyopathy, ejection fraction is normal or increased, and force-length relations are reduced. However, three-dimensional (3D) motion and deformation in vivo have not been assessed in this condition. We have reconstructed the 3D motion of the left ventricle (LV) during systole in 7 patients with hypertrophic cardiomyopathy (HCM) and 12 normal volunteers by use of magnetic resonance tagging. METHODS AND RESULTS: Transmural tagging stripes were automatically tracked to subpixel resolution with an active contour model. A 3D finite-element model was used to interpolate displacement information between short- and long-axis slices and register data on a regional basis. Displacement and strain data were averaged into septal, posterior, lateral, and anterior regions at basal, midventricular, and apical levels. Radial motion (toward the central long axis) decreased slightly in patients with HCM, whereas longitudinal displacement (parallel to the long axis) of the base toward the apex was markedly reduced: 7.5 +/- 2.5mm (SD) versus 12.5 +/- 2.0 mm, P < .001. Circumferential and longitudinal shortening were both reduced in the septum (P < .01 at all levels). The principal strain associated with 3D maximal contraction was slightly depressed in many regions, significantly in the basal septum (-0.18 +/- 0.05 versus -0.22 +/- 0.02, P < .05) and anterior (-0.20 +/- 0.05 versus -0.23 +/- 0.02, P < .05) walls. In contrast, LV torsion (twist of the apex about the long axis relative to the base) was greater in HCM patients (19.9 +/- 2.4 degrees versus 14.6 +/- 2.7 degrees, P < .01). CONCLUSIONS: HCM patients had reduced 3D myocardial shortening on a regional basis; however, LV torsion was increased.     

Urinary excretion of arsenic species after exposure to arsenic present in drinking water

The effects of intravenous MS-551, a new class III antiarrhythmic drug, on atrium and ventricle were evaluated in 6 patients with ventricular tachyarrhythmias (4 males and 2 females; mean age 45 +/- 21 years) in an electrophysiologic study. Two patients had sustained ventricular tachycardia (VT) and 4 patients had ventricular fibrillation (VF). Electrophysiologic study was performed before and after the administration of MS-551 (loading infusion 0.3 mg/kg for 5 min + 0.01 mg/kg/min). The QT and QTc intervals were significantly prolonged by MS-551 from 359 +/- 52 to 411 +/- 63 msec (p = 0.01) and from 410 +/- 36 to 452 +/- 47 (p = 0.0172), respectively. No effect was observed on the sinus cycle length, QRS duration, or AH and HV intervals in sinus rhythm. The effective refractory periods of the right atrium (AERP) were significantly prolonged at paced cycle lengths of 600 (from 222 +/- 19 to 250 +/- 23 msec, p = 0.0009), 400 (from 207 +/- 15 to 228 +/- 15, p < 0.0001) and 300 (from 193 +/- 10 to 205 +/- 8 msec, p = 0.0127) msec. Similarly, the right ventricular ERP (VERP) were significantly prolonged at paced cycle lengths of 600 (from 240 +/- 23 to 268 +/- 23 msec, p < 0.0001), 400 (from 225 +/- 22 to 250 +/- 24 msec, p = 0.0007), and 300 msec (from 213 +/- 14 to 228 +/- 18 msec, p = 0.0071). MS-551 prolonged AERP and VERP in a "reverse" use-dependent manner without changing the conduction time in patients with ventricular tachyarrhythmias. MS-551 prevented the induction of VT in 1 patient and VF in only 1 patient in this electrophysiologic study. Further evaluation of the therapeutic potential of MS-551 using higher dosages is necessary.     

Verapamil-sensitive left anterior fascicular ventricular tachycardia: results of radiofrequency ablation in six patients

INTRODUCTION: Verapamil-sensitive left ventricular tachycardia (VT) with a right bundle branch block (RBBB) configuration and left-axis deviation has been demonstrated to arise from the left posterior fascicle, and can be cured by catheter ablation guided by Purkinje potentials. Verapamil-sensitive VT with an RBBB configuration and right-axis deviation is rare, and may originate in the left anterior fascicle. METHODS AND RESULTS: Six patients (five men and one woman, mean age 54+/-15 years) with a history of sustained VT with an RBBB configuration and right-axis deviation underwent electrophysiologic study and radiofrequency (RF) ablation. VT was slowed and terminated by intravenous administration of verapamil in all six patients. Left ventricular endocardial mapping during VT identified the earliest ventricular activation in the anterolateral wall of the left ventricle in all patients. RF current delivered to this site suppressed the VT in three patients (ablation at the VT exit). The fused Purkinje potential was recorded at that site, and preceded the QRS complex by 35, 30, and 20 msec, with pace mapping showing an optimal match between the paced rhythm and the clinical VT. In the remaining three patients, RF catheter ablation at the site of the earliest ventricular activation was unsuccessful. In these three patients, Purkinje potential was recorded in the diastolic phase during VT at the mid-anterior left ventricular septum. The Purkinje potential preceded the QRS during VT by 66, 56, and 63 msec, and catheter ablation at these sites was successful (ablation at the zone of slow conduction). During 19 to 46 months of follow-up (mean 32+/-9 months), one patient in the group of ablation at the VT exit had sustained VT with a left bundle branch block configuration and an inferior axis, and one patient in the group of ablation at the zone of slow conduction experienced typical idiopathic VT with an RBBB configuration and left-axis deviation. CONCLUSION: Verapamil-sensitive VT with an RBBB configuration and right-axis deviation originates close to the anterior fascicle. RF catheter ablation can be performed successfully from the VT exit site or the zone of slow conduction where the Purkinje potential was recorded in the diastolic phase.     

Comparison of the effects of atrial and ventricular stimulation on sinus node function in man

Although sinus node function has been evaluated during premature atrial stimulation, no study of retrograde ventriculoatrial sinus node activation following premature ventricular stimuli has been reported. The purpose of this study was to investigate the production of compensatory and noncompensatory pauses by premature ventricular contractions through a comparison of the effects of atrial and ventricular stimulation on sinus node function. Eleven patients in sinus rhythm were studied with programmed introduction of premature atrial and ventricular stimuli outside the ventricular vulnerable period. The onset of sinus node reset, duration of return sinus cycle (A2-A3) during reset, and estimated sinoatrial conduction times were recorded. Sinus node function during premature ventricular stimulation was approximated by utilizing the interval between the last sinus beat and onset of retrograde atrial depolarization (A1-A2 interval). The return cycle length (A2-A3) during sinus reset compared at equal A1-A2 intervals was significantly less with ventriculoatrial conduction (1,145 +/- 52 msec. atrial vs. 1,076 +/- 52 msec ventriculoatrial; P less than 0.01 by paired t test) and the estimated sinoatrial conduction time was significantly less with ventriculoatrial conduction (71 +/- 7 msec. atrial vs. 25 +/- 7 msec. ventriculoatrial; P less than 0.01 by paired t test). Ventriculoatrial sinus reset occurred later in the sinus cycle than atrial reset in three of seven patients with sinus reset produced by both atrial and ventricular prematures. This study shows that the effects of ventriculoatrial conduction on sinus node function are significantly different from those of atrial stimulation alone. The return sinus cycle length during reset and estimated sinoatrial conduction time are significantly reduced with ventriculoatrial conduction. Although the zones of sinus reset with atrial and ventricular stimulation are approximately equal, ventriculoatrial depolarization may produce sinus reset later in the sinus cycle in some cases.     

QRS duration widening: reduced synchronization of endocardial activation or transseptal conduction time?

Antegrade activation of the His-Purkinje system (HPS) results in synchronized activation of the right ventricular (RV) and left ventricular (LV) endocardia forming normal, narrow QRS duration (QRSD). An alteration in septal activation and transseptal conduction time have been reported to be the causes for QRSD widening seen with bundle branch block. However, reduced synchronization of activation of RV and LV endocardia as another potential mechanism for QRSD widening has not been systematically studied. Fifteen consecutive patients underwent radiofrequency ablation (RFA) for treatment of supraventricular tachycardia. After RFA, mean QRSD in normal sinus rhythm was 86 +/- 8 ms with mean HV interval of 40 +/- 5 ms. Right atrial (RA), coronary sinus (CS), simultaneous (S) RA-CS, RV apex (RVA), LV apex (LVA), and SRVA-LVA pacing were performed. Mean QRSD with RA, CS, SRA-CS pacing was similar to normal sinus rhythm (87 +/- 7, 87 +/- 8 and 88 +/- 8 ms respectively). Mean QRSD was significantly longer with SRVA-LVA and either RVA or LVA pacing alone compared to normal sinus rhythm (106 +/- 8, 146 +/- 12 and 157 +/- 13 ms, respectively). However, QRSD was significantly shorter with SRVA-LVA pacing compared to either RVA or LVA pacing alone (P < 0.0001). We conclude that shorter QRSD with SRVA-LVA pacing compared to either RVA or LVA pacing alone is due to elimination of transseptal conduction delay; longer QRSD with SRVA-LVA pacing compared to sinus or atrial paced rhythm is due to reduced synchronization of endocardial activation secondary to ectopic entry of impulses into the HPS network and inability to take advantage of the branching structure of the HPS. Therefore, in addition to transseptal conduction delay, reduced synchronization of endocardial activation is another potential mechanism for QRSD widening.     

Effects of short-term altitude training and tapering on left ventricular morphology in elite swimmers

Short or long-term athletic training has been associated with left ventricular (LV) morphological adaptations, including increases in wall thickness, cavity dimension and estimated LV mass. A limitation of previous studies assessing the 'athlete heart' was that exercise training was performed at sea level. Since the 1968 Olympic summer games a popular method of maximizing athletic performance has been to use altitude training (AT) as a means of improving sea level performance. However, the effects of short term AT and taper training on LV morphology have not been well studied. Based on this limitation, the effects of three weeks of intense AT (1848 m) or low level control training (CT) (1050 m) followed by two weeks of taper training were investigated in 15 elite swimmers between 16 and 21 years of age. Short term AT or CT training followed by two weeks of taper training was not associated with alterations in LV diastolic cavity dimension (AT pre 53.3 +/- 2.8 mm versus post 52.6 +/- 4.3 mm; CT pre 52.9 +/- 3.7 mm versus post 51.2 +/- 4.0 mm), ventricular septal wall thickness (AT pre 9.6 +/- 1.0 mm versus post 9.4 +/- 1.1 mm; CT pre 8.4 +/- 1.2 mm versus post 8.6 +/- 1.1 mm), estimated LV mass (AT pre 186.4 +/- 45.8 g versus post 190.0 +/- 48.2 g; CT pre 159.1 +/- 35.8 g versus post 160.1 +/- 40.8 g) or fractional shortening (AT pre 36.8 +/- 3.5% versus post 34.8 +/- 2.7%; CT pre 32.6 +/- 5.0% versus post 32.8 +/- 4.7%). However, a main time effect, independent of training intervention, was observed for posterior wall thickness (pre 8.7 +/- 1.4 mm versus post 9.3 +/- 1.1 mm, P < 0.05). Therefore, with the exception of posterior wall thickness, short term AT followed by two weeks of taper training appears not to be associated with alterations in LV morphology or systolic function.     

Paclitaxel is preferentially cytotoxic to human cervical tumor cells with low Raf-1 kinase activity: implications for paclitaxel-based chemoradiation regimens

Little is known about the association of echocardiographic estimates of right ventricular (RV) function with survival, in relation to hemodynamic and exercise-derived predictors of outcome in congestive heart failure. We prospectively studied 40 patients (age 55+/-10 years, in New York Heart Association functional class III [70%] and IV [30%]), with left ventricular (LV) ejection fraction <30%. At enrollment, all patients underwent echocardiographic evaluation of LV dimensions and function. RV shortening was measured as the difference of the end-diastolic distance - the end-systolic distance between the tricuspid annulus and the RV apex. Thirty-five patients (88%) were able to perform a maximal symptom-limited exercise test. Peak oxygen consumption (peak VO2) and percent peak age- and gender-adjusted predicted oxygen consumption (%peak VO2) were calculated. Of 40 patients, 10 died during a mean follow-up period of 14+/-10 months. On univariate analysis, nonsurvivors had lower RV shortening (p=0.0001), higher pulmonary artery wedge pressure (p=0.009), higher pulmonary vascular resistance (p=0.02), and lower mean aortic pressure (p=0.05). Cox proportional-hazards model revealed that the only independent associate of survival was RV shortening (p=0.0005), with a trend toward significance for mean aortic pressure (p=0.08). The best cutoff point of RV shortening identified by the receiver-operating curve was 1.25 cm. This value had a sensitivity of 90%, specificity of 80%, and overall predictive accuracy of 83% to distinguish survivors from nonsurvivors. In patients with advanced heart failure, preserved RV function as indicated by an echocardiographically derived RV shortening > 1.25 cm is a strong predictor of survival.     

Right atrial and right ventricular transmural pressures in dogs and humans. Effects of the pericardium

BACKGROUND: To determine the transmural pressure-dimension relations of the right atrium (RA) and right ventricle (RV) before and after pericardiectomy, six open-chest dogs were instrumented with pericardial balloons placed over the RA and RV free walls. METHODS AND RESULTS: PA appendage dimensions and RV free-wall segment lengths were measured using sonomicrometry. Intact-pericardium RA and RV transmural pressures were calculated by subtracting the pericardial pressures (measured using balloons) from the cavitary pressures. Pooled data from six animals with pericardium intact indicate that at RA and RV cavitary pressures of 5, 10, and 15 mm Hg, RV pericardial pressure was 4.3 +/- 0.3, 8.6 +/- 1.0, and 13.3 +/- 1.5 mm Hg, respectively, and RA pericardial pressure was 4.8 +/- 0.3, 9.6 +/- 0.6, and 14.6 +/- 0.6 mm Hg, respectively (mean +/- SD). With calculated unstressed dimensions, the cavity dimension data were normalized to strain (in percent). We determined that in the dog, RV strain would increase by 14% and RA by 68% to maintain cavitary pressure at 10 mm Hg on pericardiectomy. To compare these results with clinical data, RV (n = 7) and RA (n = 6) transmural pressures were measured using balloons in patients (age, 19 to 76 years) undergoing cardiac surgery. RA transmural pressure of six patients was 1.0 +/- 1.5 mm Hg when central venous pressures (CVPs) ranged from 3 to 16 mm Hg. RV transmural pressure equaled 1.2 +/- 1.9, 2.3 +/- 1.9, and 3.4 +/- 2.0 mm Hg when CVP was 5, 10, and 15 mm Hg, respectively. CONCLUSIONS: Pericardial constraint (as evaluated by the ratio of pericardial to intracavitary pressures when CVP is 10 mm Hg) accounted for 96% of RA cavitary pressure in the dog and 89% in humans and at least 86% of RV cavitary pressure in the dog and 77% in humans.     

Reversibility of changes in left and right ventricular geometry and hemodynamics in pulmonary hypertension. Echocardiographic characteristics before and after pulmonary thromboendarterectomy

Pulmonary thromboendarterectomy (PTE) leads to an acute decrease of right ventricular (RV) afterload in patients with chronic thromboembolic pulmonary hypertension. We investigated the changes in right and left ventricular (LV) geometry and hemodynamics by means of transthoracic echocardiography. The prospective study was performed in 14 patients (8 female, 6 male; age 55 +/- 20 years) before and 18 +/- 12 days after PTE. Total pulmonary vascular resistance and systolic pulmonary artery pressure were significantly decreased (PVR: preoperative 986 +/- 318, postoperative 323 +/- 280 dyn x s/cm5, p < 0.05; PAP preoperative 71 +/- 40, postoperative 41 +/- 40 mm Hg + right atrial pressure, p < 0.05). End diastolic and end systolic RV area decreased from 33 +/- 12 to 23 +/- 8 cm2, respectively, from 26 +/- 10 to 16 +/- 6 cm2, p < 0.05. There was an increase in systolic RV fractional area change from 20 +/- 12 to 30 +/- 16%, p < 0.05. RV systolic pressure rise remained unchanged (516 +/- 166 vs. 556 +/- 128 mm Hg/sec). LV ejection fraction remained within normal ranges (64 +/- 16 vs. 62 +/- 12%). Echocardiographically determined cardiac index increased from 2.8 +/- 0.74 to 4.1 +/- 1.74 l/min/m2. A decrease in LV excentricity indices (end diastolic: 1.9 +/- 1 vs. 1.1 +/- 0.3, end systolic: 1.7 +/- 0.6 vs. 1.1 +/- 0.4, p < 0.05) proved a normalization of preoperatively altered septum motion. LV diastolic filling returned to normal limits: (E/A ratio: 0.62 +/- 0.34 vs. 1.3 +/- 0.8; p < 0.05); Peak E velocity: 0.51 +/- 0.34 vs. 0.88 +/- 0.28 m/sec, p < 0.05; Peak A velocity: 0.81 +/- 0.36 vs. 0.72 +/- 0.42 m/sec, ns; E deceleration velocity: 299 +/- 328 vs. 582 +/- 294 cm/sec2, p < 0.05; Isovolumic relaxation time: 134 +/- 40 vs. 83 +/- 38 m/sec, p < 0.05). We could show a marked decrease in RV afterload shortly after PTE with a profound recovery of right ventricular systolic function--even in case of severe pulmonary hypertension. A decrease in paradoxic motion of the interventricular septum and normalization of LV diastolic filling pattern resulted in a significant increase of cardiac index.     

Left ventricular dysfunction following rewarming from experimental hypothermia

This study was aimed at elucidating whether ventricular hypothermia-induced dysfunction persisting after rewarming the unsupported in situ dog heart could be characterized as a systolic, diastolic, or combined disturbance. Core temperature of 8 mongrel dogs was gradually lowered to 25 degreesC and returned to 37 degreesC over a period of 328 min. Systolic function was described by maximum rate of increase in left ventricular (LV) pressure (dP/dtmax), relative segment shortening (SS%), stroke volume (SV), and the load-independent contractility index, preload recruitable stroke work (PRSW). Diastolic function was described by the isovolumic relaxation constant (tau) and the LV wall stiffness constant (Kp). Compared with prehypothermic control, a significant decrease in LV functional variables was measured at 25 degreesC: dP/dtmax 2,180 +/- 158 vs. 760 +/- 78 mmHg/s, SS% 20.1 +/- 1.2 vs. 13.3 +/- 1.0%, SV 11.7 +/- 0.7 vs. 8.5 +/- 0.7 ml, PRSW 90.5 +/- 7.7 vs. 29.1 +/- 5.9 J/m. 10(-2), Kp 0.78 +/- 0.10 vs. 0.28 +/- 0.03 mm-1, and tau 78.5 +/- 3.7 vs. 25.8 +/- 1.6 ms. After rewarming, the significant depression of LV systolic variables observed at 25 degreesC persisted: dP/dtmax 1,241 +/- 108 mmHg/s, SS% 10.2 +/- 0.8 J, SV 7.3 +/- 0.4 ml, and PRSW 52.1 +/- 3.6 m. 10(-2), whereas the diastolic values of Kp and tau returned to control. Thus hypothermia induced a significant depression of both systolic and diastolic LV variables. After rewarming, diastolic LV function was restored, in contrast to the persistently depressed LV systolic function. These observations indicate that cooling induces more long-lasting effects on the excitation-contraction coupling and the actin-myosin interaction than on sarcoplasmic reticulum Ca2+ trapping dysfunction or interstitial fluid content, making posthypothermic LV dysfunction a systolic perturbation.     

Differential effect of adenosine on anterograde and retrograde fast pathway conduction in patients with atrioventricular nodal reentrant tachycardia

INTRODUCTION: Several studies have shown that the fast pathway is more responsive to adenosine than the slow pathway in patients with AV nodal reentrant tachycardia. Little information is available regarding the effect of adenosine on anterograde and retrograde fast pathway conduction. METHODS AND RESULTS: The effects of adenosine on anterograde and retrograde fast pathway conduction were evaluated in 116 patients (mean age 47 +/- 16 years) with typical AV nodal reentrant tachycardia. Each patient received 12 mg of adenosine during ventricular pacing at a cycle length 20 msec longer than the fast pathway VA block cycle length and during sinus rhythm or atrial pacing at 20 msec longer than the fast pathway AV block cycle length. Anterograde block occurred in 98% of patients compared with retrograde fast pathway block in 62% of patients (P < 0.001). Unresponsiveness of the retrograde fast pathway to adenosine was associated with a shorter AV block cycle length (374 +/- 78 vs 333 +/- 74 msec, P < 0.01), a shorter VA block cycle length (383 +/- 121 vs 307 +/- 49 msec, P < 0.001), and a shorter VA interval during tachycardia (53 +/- 23 vs 41 +/- 17 msec, P < 0.01). CONCLUSION: Although anterograde fast pathway conduction is almost always blocked by 12 mg of adenosine, retrograde fast pathway conduction is not blocked by adenosine in 38% of patients with typical AV nodal reentrant tachycardia. This indicates that the anterograde and retrograde fast pathways may be anatomically and/or functionally distinct. Unresponsiveness of VA conduction to adenosine is not a reliable indicator of an accessory pathway.     

Role of co-stimulation in CD8+ T cell activation

This study was undertaken to determine whether dl-sotalol can prevent ventricular tachyarrhythmia inducibility that can be predicted from electrophysiologic parameters. The effects of dl-sotalol in 16 patients (ventricular tachycardia (VT) in 11 and fibrillation (VF) in 5) were determined in electrophysiologic studies before and after dl-sotalol (320 mg/day). In 9 of 16 patients (56%) after dl-sotalol, ventricular tachyarrhythmia could not be induced by the entire stimulation protocol (responders). There were significant differences in QT interval (462 +/- 52 vs. 415 +/- 34 msec; p < 0.05) and ventricular effective refractory period (VERP) at 600, 400 and 300 msec (302 +/- 28 vs. 262 +/- 20 msec; p < 0.001, 280 +/- 23 vs. 240 +/- 21 msec; p < 0.001, 256 +/- 24 vs. 222 +/- 12 msec; p < 0.005, respectively) between responders and non-responders. The percentile increases in VERP (% VERP) at 600, 400, and 300 msec in responders were 25%, 26%, and 27%, whereas those in non-responders was 9%, 7%, and 7%, respectively. Isoproterenol administered to responders did not fully reverse the dl-sotalol-induced prolongation of VERP (delta VERP) at 600, 400, and 300 msec, which remained significantly prolonged compared to the baseline (281 +/- 18 vs. 241 +/- 16 msec; p < 0.01, 258 +/- 20 vs. 223 +/- 21 msec; p < 0.01, 247 +/- 22 vs. 202 +/- 16 msec; p < 0.01, respectively). % VERP did not exhibit significant differences at 600 (16%), 400 (15%), and 300 (20%) msec, indicating the lack of a reverse use-dependency. The results suggest that delta VERP in responders did not show reverse use-dependency, and that the phenomenon may account for the efficacy of dl-sotalol.     

Spectrum of clinicopathologic manifestations of arrhythmogenic right ventricular cardiomyopathy/dysplasia: a multicenter study

OBJECTIVES: The aim of the present investigation was to redefine the clinicopathologic profile of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC), with special reference to disease progression and left ventricular (LV) involvement. BACKGROUND: Long-term follow-up data from clinical studies indicate that ARVC is a progressive heart muscle disease that with time may lead to more diffuse right ventricular (RV) involvement and LV abnormalities and culminate in heart failure. METHODS: Forty-two patients (27 male, 15 female; 9 to 65 years old, mean [+/-SD] age 29.6 +/- 18) from six collaborative medical centers, with a pathologic diagnosis of ARVC at autopsy or heart transplantation, and with the whole heart available, were studied according to a specific clinicomorphologic protocol. RESULTS: Thirty-four patients died suddenly (16 during effort); 4 underwent heart transplantation; 2 died as a result of advanced heart failure; and 2 died of other causes. Sudden death was the first sign of disease in 12 patients; the other 30 had palpitations, with syncope in 11, heart failure in 8 and stroke in 3. Twenty-seven patients experienced ventricular arrhythmias (ventricular tachycardia in 17), and 5 received a pacemaker. Ten patients had isolated RV involvement (group A); the remaining 32 (76%) also had fibrofatty LV involvement that was observed histologically only in 15 (group B) and histologically and macroscopically in 17 (group C). Patients in group C were significantly older than those in groups A and B (39 +/- 15 years vs. 20 +/- 8.8 and 25 +/- 9.7 years, respectively), had significantly longer clinical follow-up (9.3 +/- 7.3 years vs. 1.2 +/- 2.1 and 3.4 +/- 2.2 years, respectively) and developed heart failure significantly more often (47% vs. 0 and 0, respectively). Patients in groups B and C had warning symptoms (80% and 87%, respectively, vs. 30%) and clinical ventricular arrhythmias (73% and 82%, respectively, vs. 20%) significantly more often than patients in group A. Hearts from patients in group C weighed significantly more than those from patients in groups A and B (500 +/- 150 g vs. 328 +/- 40 and 380 +/- 95 g, respectively), whereas hearts from both group B and C patients had severe RV thinning (87% and 71%, respectively, vs. 20%) and inflammatory infiltrates (73% and 88%, respectively, vs. 30%) significantly more often than those from group A patients. CONCLUSIONS: LV involvement was found in 76% of hearts with ARVC, was age dependent and was associated with clinical arrhythmic events, more severe cardiomegaly, inflammatory infiltrates and heart failure. ARVC can no longer be regarded as an isolated disease of the right ventricle.     

Impaired regional fatty acid uptake and systolic dysfunction in hypertrophied right ventricle

Little information is available regarding the determinants of systolic contractile function of the hypertrophied right ventricle (RV). The purpose of this study was to clarify the relationship between myocardial metabolism and contractile function in the hypertrophied RV due to pulmonary hypertension (PH). METHODS: Iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and 99mTc-sestamibi (MIBI) SPECT were performed to calculate the RV-to-left ventricle (LV) tracer uptake ratio (RV/LV) in 21 patients with PH (6 with primary PH and 15 with chronic thromboembolic PH). The patients also underwent electron-beam CT to assess RV ejection function (RVEF) and percentage systolic wall thickening (%SWT) and right heart catheterization to measure mean pulmonary arterial pressure (mPAP). RESULTS: There were significant positive correlations between mPAP and MIBI-RV/LV (r = 0.89, p < 0.001) and between mPAP and BMIPP-RV/LV (r = 0.86, p < 0.001). However, 8 patients showed lower BMIPP-RV/LV than MIBI-RV/LV, indicating the impairment of myocardial fatty acid uptake in the RV. These patients had lower RVEF and %SWT compared to those with normal myocardial fatty acid uptake (RVEF = 28% +/- 10% compared to 40% +/- 9% and %SWT = 33% +/- 27% compared to 74% +/- 30%, respectively; p < 0.05 for both comparisons). Although mPAP did not differ between the groups, the RVEF-mPAP and %SWT-mPAP regression lines drawn from the patients with impaired myocardial fatty acid uptake were located below the lines from the patients with normal myocardial fatty acid uptake, suggesting disproportionately decreased RV myocardial contractility for a given mPAP in patients with impaired myocardial fatty acid uptake. The patients with the impaired fatty acid uptake in the RV had a significantly higher death rate (log-rank test, p < 0.05). CONCLUSION: The results from this preliminary study suggest that myocardial fatty acid uptake is impaired in the failing hypertrophied RV due to PH.     

Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography

Transfusion-dependent (TD) patients develop cardiac iron overload that will eventually lead to cardiac pump failure. Low-dose dobutamine stress echocardiography may complement resting echocardiography and identify preclinical myocardial dysfunction caused by early cardiac hemosiderosis. Twenty-six iron-overloaded TD patients had stress echocardiography with 5 microg/kg per minute of dobutamine. Indexed left ventricular (LV) mass, LV dimensions, meridional wall stress, and cardiac index were significantly increased. TD patients had similar LV shortening fraction by M-mode (40.5% +/- 5.6% vs 39.4% +/- 4.5%) but had a lower mean LV ejection fraction (53.3% +/- 3.9% vs 46.8% +/- 6.9%, P < .002) and a subnormal increase in cardiac index during dobutamine stress (35% +/- 20% vs 11% +/- 16%, P < .0001). Impairment in LV relaxation was demonstrated by a prolonged isovolumetric relaxation time (0.060 +/- 0.005 vs 0.088 +/- 0.019 seconds, P < .0001), increased peak mitral E wave, and abnormal E/A ratio. Asymptomatic TD patients demonstrate decreased systolic functional reserve and abnormal left ventricular relaxation that may be caused by cardiac hemosiderosis. Low-dose dobutamine stress echocardiography may be useful for detecting and following cardiac dysfunction in patients at risk for cardiac hemosiderosis.     

Assessment of right ventricular function and interstitial fibrosis in idiopathic dilated cardiomyopathy: hemodynamic correlates and prognostic value

BACKGROUND: Right ventricular (RV) function and morphometric quantitation of interstitial fibrosis in idiopathic dilated cardiomyopathy (IDC) have not been the subject of specifically designed clinical observations. In particular, their role in routine assessment and prognostic evaluation of patients (pts) with IDC remains to be settled. METHODS: Eighty-one consecutive IDC patients (63 M, 18 F; mean age 52 +/- 11 yrs) with left ventricular (LV) systolic dysfunction (angiographic ejection fraction - EF - < 55%), normal coronary arteries and no histologic evidence of myocarditis were studied. Cardiac catheterization and endomyocardial biopsy (EMB) were routinely performed in all cases. RV volumes and EF were obtained by angiography according to Ferlinz' method and interstitial fibrosis was quantitated by computer-assisted morphometric analysis. These data were analyzed in order to study correlations with hemodynamic parameters and to assess their prognostic value in a long-term follow-up. RESULTS: In the study population, right ventricular EF was significantly lower than in normal controls (35 +/- 11% vs 53 +/- 6%, p < 0.0001) and showed a significant positive correlation with LV EF (r = 0.54; p < 0.0001), and a weak but significant negative correlation with fibrosis (r = -0.29; p = 0.03). RV volumes, but not EF, were significantly related to mean pulmonary pressure. At multivariate analysis, RV end-diastolic volume (EDV) and EF were the two independent predictors of severe heart failure (NYHA class III-IV). After a mean follow-up of 64 +/- 36 months, 20 pts died and 9 had heart transplantation, for a 63% transplant-free survival rate (TFS). Multivariate analysis identified three independent predictors of TFS: LV stroke work index (p < 0.0001), RV stroke work index (p = 0.02) and RV EDV (p = 0.03). Fibrosis was predictive of survival only in the subgroup with LV EF < 20%. CONCLUSIONS: Assessment of RV function provides useful information in the evaluation of hemodynamic profile and prognosis of pts with IDC. Quantitation of interstitial fibrosis by morphometry provides little additional data.     

Effect of relatively low dose amiodarone therapy on left ventricular function in patients with ventricular tachyarrhythmias

The effect of oral amiodarone (AMD) therapy on left ventricular (LV) function was evaluated retrospectively in Japanese patients with ventricular tachyarrhythmias and congestive heart failure. Seventeen patients were treated with oral AMD (maintenance dose 191+/-52mg/day) for more than 12 months. Fractional shortening (FS) on echocardiography revealed a trend towards an increase in the short-term (3 months) (p=0.06), but was not significant in the long-term follow-up period (more than 12 months) after AMD therapy. In 8 patients with 1 episode of myocardial infarction, FS revealed a trend towards an increase (p=0.09). In all of the 4 patients with dilated cardiomyopathy whose LV end-diastolic diameter was increased, FS was decreased in the long-term follow-up. Neither hospitalization frequency nor New York Heart Association classification were reduced by AMD therapy. In conclusion,oral AMD therapy did not cause LV function to recover significantly and could not improve the clinical course in patients with ventricular tachyarrhythmias. However, if the underlying disease is not progressive, AMD therapy may improve LV function.