Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction

BACKGROUND: Recent clinical trials have suggested that therapy with angiotensin-converting enzyme inhibitors in asymptomatic patients with reduced left ventricular (LV) function can significantly reduce the incidence of congestive heart failure compared with patients receiving placebo. In the present study, we examined the effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF). METHODS AND RESULTS: LV dysfunction was produced in 28 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after the last embolization, dogs were randomized to 3 months of oral therapy with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n = 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n = 7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/- 1%, P < .001) and LV end-systolic volume (ESV) and end-diastolic volume (EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/- 6 mL, P < .001, and 61 +/- 6 versus 78 +/- 8 mL, P < .002, respectively). In dogs treated with enalapril or metoprolol, LVEF remained unchanged or increased after therapy compared with before therapy (35 +/- 1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P < .05), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased significantly. CONCLUSIONS: In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfunction and LV chamber dilation. Therapy with digoxin maintains LV systolic function but does not prevent progressive LV enlargement.     

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.     

Angiotensin II activates distinct signal transduction pathways in astrocytes isolated from neonatal rat brain

The aim of the study was to assess whether the hypotensive activity of amlodipine is associated with regression of left ventricular hypertrophy and improvement of impaired LV or right ventricular (RV) diastolic function or increasing of tolerance of physical activity in hypertensive patients. Assessment of left ventricular structure, systolic and diastolic function as well as RV diastolic dimension and diastolic function were performed in 24 patients with mild-to-moderate hypertension before administration of amlodipine and 3, 6 and 9 months of the treatment. In order to assess the tolerance of physical activity, incremental treadmill exercise testing was performed at baseline and after 6 and 9 months of the therapy with amlodipine. RESULTS: During 9 months of the therapy with amlodipine no significant change in indexes of LV mass or in LVM was observed. Similarly amlodipine did not influence the parameters of LV or RV diastolic function in studied patients. However, amlodipine treatment resulted in significant increase in total exercise time (p < 0.05), total workload (p < 0.01) measured in METs and decrease in diastolic blood pressure during exercise test. CONCLUSION: The nine months of the therapy with amlodipine resulted in significant improvement in exercise tolerance. Total exercise duration and total workload measured in METs significantly increased. During this time of the therapy no significant changes in LV structure or LV and RV diastolic function were observed. One can make an assumption that amlodipine inhibits progression of structural and functional derangement in hypertensive patients.     

Effects of partial left ventriculectomy on left ventricular performance in patients with nonischemic dilated cardiomyopathy

OBJECTIVES: This study sought to assess the effects of partial left ventriculectomy (PLV) on left ventricular (LV) performance in a series of consecutive patients with nonischemic dilated cardiomyopathy. BACKGROUND: Reduction of LV systolic function in patients with heart failure is associated with an increase of LV volume and alteration of its shape. Recently, PLV, a novel surgical procedure, was proposed as a treatment option to alter this process in patients with dilated cardiomyopathy. METHODS: We studied 19 patients with severely symptomatic nonischemic dilated cardiomyopathy, before and 13+/-3 days after surgery, and 12 controls. Single-plane left ventriculography with simultaneous measurements of femoral artery pressure was performed during right heart pacing. RESULTS: The LV end-diastolic and end-systolic volume indexes decreased after PLV (from 169 to 102 ml/m2, and from 127 to 60 ml/m2, respectively, p < 0.0001 for both). Despite a decrease in LV mass index (from 162 to 137 g/m2, p < 0.0001), there was a significant decrease in LV circumferential end-systolic and end-diastolic stresses (from 277 to 159 g/cm2, p < 0.0001 and from 79 to 39 g/cm2, p = 0.0014, respectively). Ejection fraction improved (from 24% to 41%, p < 0.0001); the stroke work index remained unchanged. CONCLUSIONS: The PLV improves LV performance by a dramatic reduction of ventricular end-systolic and end-diastolic stresses. Further studies are needed to assess whether this effect is sustained during long-term follow-up and to define the role of PLV in the treatment of patients with dilated cardiomyopathy.     

Recovery of cardiac function by long-term left ventricular support in patients with end-stage cardiomyopathy

Effects of long-term left ventricular (LV) support on end-stage cardiomyopathy patients is unclear. We applied our LV assist system (LVAS) to six heart transplant candidates, aged 17 to 49, with dilated cardiomyopathy, including one dilated phase hypertrophied cardiomyopathy. LVAS was installed between the left atrium and the ascending aorta, and the pump was positioned parecorporeally. In all patients, their general condition improved, and their pump flows were kept at 4 to 5 L/min. Exercise was started after stabilization of their general condition under constant pump flow. Natural heart size and function were examined by echocardiography. In the beginning of assist, all patients showed impaired cardiac function and LV dilation. During LV assist, systolic function measured by ejection time improved in all patients. Left ventricular end-diastolic dimension (LVDd), showed a remarkable decrease in two patients, who were weaned from LVAS after 3 months of support. They are doing well more than 1 year and 3 years after removal; peak VO2 levels (ml/min/kg) were 30 at 1.2 years and 27 at 2.7 years after removal. In the other four patients, however, LVDd had no remarkable changes, and three could not be weaned from LVAS. The last was discontinued from LVAS after 5 months of support because of infection and died 2 months after removal. From this experience, long-term LVAS may provide the chance for recovery of the natural heart in patients with end-stage cardiomyopathy. The patients whose hearts showed remodeling were able to be weaned from LVAS, and their heart function maintained in good condition for several years.     

One-year effect of myocardial revascularization on resting left ventricular function and regional thallium uptake in chronic CAD

It is still unclear whether in patients with chronic coronary artery disease (CAD) the improvements in myocardial perfusion and left ventricular (LV) function induced by revascularization persist in the long run. This study was planned to evaluate the 1-yr effects of successful revascularization on myocardial perfusion and LV function in patients with CAD and to assess the accuracy of thallium imaging in the prediction of functional recovery 1 yr after revascularization. METHODS: Thirty-eight patients with chronic CAD who were revascularized (experimental group) underwent, while off drugs, 201Tl tomography, two-dimensional echocardiography and radionuclide angiography before and after a 1-yr follow-up. Twenty-nine patients with similar characteristics who were not revascularized (control group) and completed the 1-yr follow-up were also studied. Regional thallium activity was quantitatively measured in 13 segments per patient. Systolic function was assessed by echocardiography in corresponding segments. RESULTS: In the experimental group, at baseline, on the basis of regional LV function and thallium uptake, 276 segments were normal, 169 dysfunctional-viable and 49 nonviable. After revascularization, the majority (75%) of the dysfunctional-viable segments at baseline showed functional recovery at follow-up, whereas the majority (81%) of the nonviable segments at baseline did not. Simultaneously, LV ejection fraction increased 4 wk after revascularization (from 39% +/- 9% to 42% +/- 10%, p < 0.01) and remained unchanged after 1-yr (43% +/- 8%, p < 0.01 versus baseline study). LV wall-motion score index after 1 yr was reduced (from 1.68 +/- 0.4 to 1.42 +/- 0.3, p < 0.001) as compared with baseline. On the contrary, in the control group, no change in myocardial perfusion and LV function was detected after the 1-yr follow-up. CONCLUSION: In patients with chronic CAD, successful coronary revascularization induces a stable improvement in myocardial perfusion and LV function, which is still detectable after a 1-yr follow-up. Furthermore, preserved thallium uptake in dysfunctional regions is predictive of functional recovery after revascularization.     

Circannual variation of malignant ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators and either coronary artery disease or idiopathic dilated cardiomyopathy

We studied the possible relation between the frequency of ventricular tachyarrhythmic events and thermal stress in patients with an implantable cardioverter-defibrillator (ICD) living in a locally limited area under homogeneous climatic conditions. The frequency of tachyarrhythmic events was correlated with the thermal stress level according to the "Klima Michel Model," a complete thermophysiologic model that calculates "felt-temperature" values on the basis of the outdoor temperature and further meteorologic data. During a mean follow-up time of 40 +/- 17 months (range 4 to 72), 761 ventricular tachyarrhythmic events occurred in 50 of 138 consecutive ICD recipients. Analysis of the monthly felt-temperature levels and the mean circannual variation of the registered ventricular arrhythmias suggested that very cold and very hot conditions may be associated with an increased frequency of ventricular tachyarrhythmias. This finding was confirmed by calculation of the sum of tachyarrhythmias on all 2,039 days of the follow-up period divided into 5-degree-step felt-temperature classes. Thus, thermal stress may be 1 factor triggering the occurrence of ventricular tachyarrhythmias in patients with cardiac disease and suppressed cardiac function. Part of the increase in cardiac mortality under above-average hot and cold atmospheric conditions may be attributed to ventricular arrhythmic events.     

T wave alternans as a predictor of recurrent ventricular tachyarrhythmias in ICD recipients: prospective comparison with conventional risk markers

INTRODUCTION: The current standard for arrhythmic risk stratification is electrophysiologic (EP) testing, which, due to its invasive nature, is limited to patients already known to be at high risk. A number of noninvasive tests, such as determination of left ventricular ejection fraction (LVEF) or heart rate variability, have been evaluated as additional risk stratifiers. Microvolt T wave alternans (TWA) is a promising new risk marker. Prospective evaluation of noninvasive risk markers in low- or moderate-risk populations requires studies involving very large numbers of patients, and in such studies, documentation of the occurrence of ventricular tachyarrhythmias is difficult. In the present study, we identified a high-risk population, recipients of an implantable cardioverter defibrillator (ICD), and prospectively compared microvolt TWA with invasive EP testing and other risk markers with respect to their ability to predict recurrence of ventricular tachyarrhythmias as documented by ICD electrograms. METHODS AND RESULTS: Ninety-five patients with a history of ventricular tachyarrhythmias undergoing implantation of an ICD underwent EP testing, assessment of TWA, as well as determination of LVEF, baroreflex sensitivity, signal-averaged ECG, analysis of 24-hour Holter monitoring, and QT dispersion from the 12-lead surface ECG. The endpoint of the study was first appropriate ICD therapy for electrogram-documented ventricular fibrillation or tachycardia during follow-up. Kaplan-Meier survival analysis revealed that TWA (P < 0.006) and LVEF (P < 0.04) were the only significant univariate risk stratifiers. EP testing was not statistically significant (P < 0.2). Multivariate Cox regression analysis revealed that TWA was the only statistically significant independent risk factor. CONCLUSIONS: Measurement of microvolt TWA compared favorably with both invasive EP testing and other currently used noninvasive risk assessment methods in predicting recurrence of ventricular tachyarrhythmias in ICD recipients. This study suggests that TWA might also be a powerful tool for risk stratification in low- or moderate-risk patients, and needs to be prospectively evaluated in such populations.     

Influence of heart rate on stroke volume variability in atrial fibrillation in patients with normal and impaired left ventricular function

Both resting tachycardia and irregular ventricular rhythm may contribute to impaired cardiac performance in atrial fibrillation (AF). This study assesses the relation between resting heart rate and beat-to-beat changes in left ventricular (LV) ejection and filling in patients with normal and impaired LV systolic function. Beat-to-beat variation in LV outflow and inflow velocity-time integral was measured using pulsed Doppler ultrasound in 39 patients with chronic AF and normal (n=22) or impaired (n=17) LV systolic function. Aortic velocity-time integral variability increased with mean heart rate (p=0.003) even though RR interval variability decreased (p <0.001). Aortic velocity-time integral was more sensitive to the duration of both the preceding (p <0.001) and prepreceding (p <0.001) RR intervals at higher heart rates. These relations were similar for patients with normal and impaired LV systolic function. The sensitivity of the filling velocity-time integral to RR interval variability also increased with heart rate (p <0.001). However, at higher heart rates the filling velocity-time integral (p=0.009) and filling time (p=0.005) were less sensitive to change in RR intervals in patients with impaired LV function. We conclude that beat-to-beat stroke volume variability in AF increases with heart rate. Stroke volume variability was not influenced by LV systolic function.     

Assessment of left ventricular function by isometric handgrip exercise after thrombolysis in patients with refractory unstable angina

The handgrip test has been proposed for the evaluation of the hemodynamic reserve in patients with coronary artery disease and to quantitate the impairment of left ventricular (LV) function. The present study was designed to evaluate the effect of thrombolytic therapy in patients with refractory unstable angina in order to test the hypothesis that a reduction in intracoronary thrombosis could ameliorate their hemodynamic response to the handgrip test. During left heart catheterization, 20 patients with refractory unstable angina of recent onset performed a handgrip test before (HG1) and 24-72 hours after (HG2) being randomized to receive recombinant tissue-type plasminogen activator or placebo, according to a double-blind parallel group design. HG1 induced an increase in heart rate (p < 0.001), in systolic pressure (p < 0.001), and a reduction in ejection fraction (p < 0.05). Changes in LV end-diastolic pressure during baseline handgrip were highly different in individual patients, resulting in a trend toward an increase. Similarly, a different individual response was observed in the behavior of the isovolumetric and relaxation indices. In comparison with HG1, no difference was detected during HG2 in the 2 treatment groups with respect to changes in LV volumes, ejection fraction, LV systolic and diastolic pressures, +dP/dt, (dP/dt)/P, -dP/dt, and tau index. In patients with refractory unstable angina of recent onset, the handgrip test performed before and after thrombolysis did not prove to be useful in assessing directional changes of LV performance, mainly because of the different individual response to the baseline handgrip test.     

Late outcome of survivors of idiopathic ventricular fibrillation

This report describes clinical, hemodynamic, and electrophysiologic characteristics of 18 consecutive survivors of sudden cardiac arrest due to idiopathic ventricular fibrillation (VF) between 1986 and 1996. Long-term data in relation to the prescribed therapy are presented. The mean age of the 18 patients was 48 +/- 14 years (median 49). Electrophysiologic studies showed a low inducibility of sustained ventricular tachyarrhythmias in 4 patients (22%). Treatment consisted of class III agents, beta blockers, or implantable cardioverter-defibrillators. Two patients were discharged without any therapy. Therapy control was undertaken either by serial drug testing or by the empirical approach. Serious complications of therapy occurred in 2 patients: 1 patient experienced a proarrhythmic effect of antiarrhythmic drug therapy, and the other patient received multiple inadequate defibrillator discharges due to a defect in the transvenous lead. All but 1 patient (94%) remained free of recurrences of sudden cardiac arrest during a follow-up time of 45 +/- 29 months (median 41). One patient died 2 weeks after surviving cardiac arrest due to intractable VF while receiving sotalol treatment. Therapy guided by electrophysiologic studies did not have any impact on survival. Adverse effects or noncompliance led to discontinuation of drug therapy in 7 patients after a mean period of 31 +/- 30 months. Without any treatment 9 patients remained without recurrences over 45 +/- 33 months. Because of the absence of risk factors for arrhythmia recurrence and criteria to select therapy, randomized prospective studies are warranted to assess the optimal therapies in these young, ostensibly healthy patients.     

Bronchodilator response to salbutamol after chronic dosing with salmeterol or placebo

OBJECTIVES: We report the occurrence of cardiac events during long-term follow-up in patients with hypertrophic cardiomyopathy (HCM) after cardioverter-defibrillator implantation. BACKGROUND: The identification of patients at high risk for sudden death and the prevention of recurrence of sudden death in HCM represents a difficult problem. METHODS: We retrospectively analyzed the occurrence of cardiac events during follow-up of 13 patients with HCM who received an implantable cardioverter-defibrillator (ICD) because of aborted sudden death (n = 10) or sustained ventricular tachycardia (n = 3) (group I). Findings were compared with those in 215 patients with an ICD and other structural heart disease or idiopathic ventricular fibrillation (group II). RESULTS: After a mean (+/-SD) follow-up period of 26+/-18 months, 2 of 13 patients in group I received appropriate shocks. The calculated cumulative incidence of shocks was 21% in group I and 66% in group II after 40 months (p < 0.05). We observed a low incidence of recurrence of ventricular tachycardia/fibrillation during follow-up in patients with HCM. No deaths occurred. CONCLUSIONS: Our data suggest that ventricular tachyarrhythmias may not always be the primary mechanism of syncope and sudden death in patients with HCM. The ICD seems to have a less important impact on prognosis in patients with HCM than in patients with other etiologies of aborted sudden death.     

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.     

Biphasic response to dobutamine predicts improvement of global left ventricular function after surgical revascularization in patients with stable coronary artery disease: implications of time course of recovery on diagnostic accuracy

OBJECTIVES: This study sought to evaluate the time course of improvement of left ventricular (LV) dysfunction in stable patients and its implications on the accuracy of dobutamine echocardiography for predicting improvement after surgical revascularization. BACKGROUND: Little is known about the optimal timing for evaluation of postrevascularization recovery of the contractile function of viable myocardium. METHODS: Sixty-one patients with chronic ischemic LV dysfunction scheduled for elective surgical revascularization were prospectively selected. They underwent dobutamine echocardiography (5 to 40 microg/kg body weight per min) and radionuclide ventriculography both preoperatively and at 3-month follow-up. At 14 months, another evaluation of LV function was obtained. To analyze echocardiograms, a 16-segment model and a five-point scoring system were used. Dyssynergic segments were considered likely to recover in the presence of a biphasic contractile response to dobutamine. Improvement of global function was defined as a > or =5% increase in LV ejection fraction (LVEF). RESULTS: Of the 61 patients, LVEF improved in 12 at 3 months and in 19 at late follow-up (from 32+/-8% to 42+/-9%, p < 0.0001). The frequency and time course of improvement of LVEF were similar in patients with mild and severe LV dysfunction. A biphasic response, identified in 186 of the 537 dyssynergic segments, was predictive of recovery in 63% at 3 months and in 75% at late follow-up. The positive predictive value was best in the most severe dyssynergic segments (90% vs. 67%). Other responses were highly predictive for nonrecovery (92%). The sensitivity and specificity for improvement of global function on a patient basis (> or =4 biphasic segments) were 89% and 81%, respectively, at late follow-up. CONCLUSIONS: Serial postoperative follow-up studies demonstrate incomplete recovery of contractile function at 3 months. The diagnostic accuracy of dobutamine echocardiography for predicting recovery is dependent on three factors: the combining of low and high dobutamine dosages, the severity of regional dyssynergy and the timing of evaluation.     

Clinical significance of sleep apnea disorders after implantation of a cardioverter-defibrillator in patients with cardiac disease and sustained ventricular tachyarrhythmia

The purpose of our study was to determine the prevalence of sleep related breathing disorders (SRBD) in patients with an implantable cardioverter-defibrillator (ICD) and to evaluate prospectively the possible influence of SRBD on arrhythmia recurrence and circadian arrhythmia variation as well as on cardiac mortality during long-term follow-up. Forty consecutive ICD recipients with cardiac disease and a documented history of spontaneous, life-threatening, ventricular tachyarrhythmias underwent full-night polysomnography and were followed for 2 years. In 16 of 40 patients (40%), SRBD were diagnosed (Apnea/Hypopnea Index (AHI) > 10); in 9 of these 16 patients (56%) central sleep apneas (CSA) occurred (in 8 of these 9 patients in combination with Cheyne-Stokes respiration). Seven of the 16 patients with SRBD (44%) revealed obstructive sleep apneas (OSA). AHI was 32 +/- 15 (12-60) in patients with CSA and 32 +/- 27 (11-86) in patients with OSA. Patients with and without SRBD were comparable concerning left ventricular ejection fraction, NYHA classification, cardiac disease, ICD indication, and concomitant medication. ICD registered ventricular tachyarrhythmias occurred in 10 of 24 patients (42%) without SRBD, in 4 of 9 patients (44%) with CSA, and in 3 of 7 patients (44%) with OSA. The numbers and circadian variation of episodes registered during follow-up in patients without SRBD, with OSA or CSA were comparable (14 +/- 25, median 4 vs 15 +/- 15, median 7 vs 4 +/- 5, median 2.5). The 2-year cardiac mortality was highest in patients with CSA (4/9 (44%) vs. 0/7 patients (0%) with OSA vs 3/24 patients (12.5%) without SRBD. Thus, the prevalence of SRBD in patients with chronic heart failure and a history of malignant ventricular tachyarrhythmias is high (40%) and the occurrence of CSA seems to be predictive for cardiac mortality in these patients. An influence of moderate SRBD on arrhythmia recurrence and circadian variation of spontaneous sustained tachyarrhythmic events could not be demonstrated.     

Predischarge two-dimensional echocardiographic evaluation of left ventricular thrombosis after acute myocardial infarction in the GISSI-3 study

Left ventricular (LV) thrombosis can be found in patients with acute myocardial infarction (AMI). No wide multicenter trial on AMI has provided information about LV thrombosis until now. The protocol of the GISSI-3 study included the search for the presence of LV thrombosis in patients from 200 coronary care units that did not specifically focus on LV thrombosis. We examined the GISSI-3 database results related to 8,326 patients at low to medium risk for LV thrombi in which a predischarge echocardiogram (9 +/- 5 days) was available. LV thrombosis was found in 427 patients (5.1%): 292 of 2,544 patients (11.5%) with anterior AMI and in 135 of 5,782 patients (2.3%) with AMI in other sites (p <0.0001). The incidence of LV thrombosis was higher in patients with ejection fraction < or = 40% (151 of 1,432 [10.5%] vs 276 of 6,894 [4%]; p <0.0001) both in the total population and in the subgroup with anterior AMI (106 of 597 [17.8%] vs 186 of 1,947 [9.6%]; p <0.0001). Multivariate analysis showed that only the Killip class > I and early intravenous beta-blocker administration were independently associated with higher LV thrombosis risk in the subgroup of patients with anterior AMI (odds ratio 1.75, 95% confidence interval 1.28 to 2.39; odds ratio 1.32, 95% confidence interval 1.02 to 1.72, respectively). In patients with anterior AMI, oral beta-blocker therapy given or not given after early intravenous beta-blocker administration does not influence the occurrence of LV thrombosis. The rate of LV thrombosis was similar in patients treated or not treated with nitrates and lisinopril both in the total population and in patients with anterior and nonanterior AMI. In conclusion, in the GISSI-3 population at low to medium risk for LV thrombi, the highest rate of occurrence of LV thrombosis was found among patients with anterior AMI and an ejection fraction < 40%. Killip class > I and the early intravenous beta-blocker administration were the only variables independently associated with a higher predischarge incidence of LV thrombosis after anterior AMI.     

Implantable cardioverter defibrillator utilization among device recipients presenting exclusively with syncope or near-syncope

INTRODUCTION: Implantable cardioverter defibrillators (ICDs) are occasionally used in presumed high-risk patients with electrocardiographically undocumented syncope, although the incidence of ventricular tachyarrhythmias in this population is not well defined. METHODS AND RESULTS: We studied 33 consecutive patients receiving an ICD (67% nonthoracotomy and 70% tiered therapy) after electrophysiologic testing for unmonitored "syncope" (n = 29) or "near-syncope" (n = 4). Atherosclerotic heart disease was present in 24 (73%); mean left ventricular ejection fraction (LVEF) was 0.39 +/- 0.15; and sustained monomorphic ventricular tachycardia (SMVT) was inducible in 18 (55%). Over a median follow-up of 17 months (range 4 to 61), 12 patients (36%) received > or = 1 appropriate ICD discharge triggered by SMVT (cycle length 230 to 375 msec) in 10 and ventricular flutter or fibrillation in 2--without concomitant antiarrhythmic medication in 8 of 12 cases. Inducible SMVT and LVEF < or = 0.35 were statistically significant, independent predictors of an appropriate ICD discharge (P < 0.02 and P < 0.03, respectively). Estimated 1-year cumulative survival free of appropriate discharge was 34% versus 87%, respectively, in patients with versus without inducible SMVT (P < 0.02), and 18% versus 56%, respectively, in patients with LVEF < or = 0.35 versus LVEF > 0.35 (P < 0.03). CONCLUSION: In this highly select, multicenter population of ICD recipients with electrocardiographically undocumented syncope, a substantial incidence of appropriate device discharges was observed, particularly in patients with inducible SMVT and LVEF < or = 0.35. These findings support the notion that, in patients with LV dysfunction and inducible SMVT, ventricular tachyarrhythmias are likely to account for episodes of syncope or near-syncope.     

Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group

OBJECTIVES: We sought to determine the efficacy of isradipine in reducing left ventricular (LV) mass and wall thickness in hypertensive patients. BACKGROUND: LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events. Reduction of LV mass may be a desirable goal of drug therapy for hypertension. However, although thiazide diuretic drugs have been advocated as first-line therapy for hypertension, their efficacy in reducing LV mass has been questioned. METHODS: Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were randomized to isradipine (n = 89) or hydrochlorothiazide therapy (n = 45). Evaluations were obtained at baseline, after 3 and 6 months of treatment and 2 weeks after treatment was stopped. RESULTS: At 6 months, LV mass decreased by 43 +/- 45 g (mean +/- SD) with hydrochlorothiazide (p < 0.001) but only by 11 +/- 48 g with isradipine (p = NS; between-group comparison, p < 0.001). Two weeks after drug therapy was stopped, LV mass remained 24 +/- 41 g lower than that at baseline in the hydrochlorothiazide group (p = 0.003) but only 7 +/- 50 g lower in the isradipine group (p = NS). Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide. Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 +/- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine. At 6 months of treatment, diastolic blood pressure (BP) by design was equally reduced in both treatment groups. At 3 months, systolic BP was reduced by 17 +/- 15 mm Hg with isradipine and by 26 +/- 15 and 25 +/- 17 mm Hg at 3 and 6 months, respectively, with hydrochlorothiazide (p = 0.003, between-group comparison). However, on stepwise multivariable regression analysis, treatment selection (partial r2 = 0.082, p = 0.001), change in average 24-h systolic BP (partial r2 = 0.032, p = 0.029) and change in average sitting systolic BP (partial r2 = 0.017, p = 0.096) were predictive of LV mass reduction. CONCLUSIONS: Despite an equivalent reduction of diastolic BP, 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass, greater than that with isradipine. The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself. These data may have important therapeutic implications.     

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.     

Long-term efficacy of d/l sotalol in patients with sustained ventricular tachycardia refractory to class I antiarrhythmic drugs

The efficacy of d/l sotalol was investigated in 50 patients (43 men, seven women; 33 with coronary artery disease, 15 with dilated cardiomyopathy; ejection fraction 33 +/- 10%) with inducible sustained ventricular tachycardia. Before d/l sotalol a mean of 2 +/- 1 (1 to 4) class I antiarrhythmic drugs were ineffective. In 24 patients (48%) oral d/l sotalol (320 +/- 47 mg.day-1) prevented induction of the ventricular tachycardia; in 23 patients the ventricular tachycardia remained inducible (d/l sotalol 326 +/- 50 mg.day-1). The electrophysiological effects of d/l sotalol did not differ between patients in whom d/l sotalol prevented induction of ventricular tachycardia and those in whom the ventricular tachycardia remained inducible. In two patients, torsade des pointes developed after oral application of d/l sotalol; one patient suffered from severe hypotension even with 80 mg of sotalol per day. During long-term follow-up (27 +/- 12 months) 5/24 patients (21%) had a non-fatal recurrence of ventricular tachycardia (1 week to 21 months), one patient died suddenly and another from progressive heart failure. In patients in whom the ventricular tachycardia could be induced despite oral application of d/l sotalol, control of the ventricular tachyarrhythmia was attempted by the use of sotalol in combination with mexiletine (n = 2), amiodarone (n = 9), catheter ablation (n = 2), antitachycardia surgery (n = 1) or the implantation of an automatic cardioverter defibrillator (n = 12). Recurrence of ventricular tachycardia was observed in four patients without an implanted cardioverter defibrillator. Seven out of 12 patients with an implanted cardioverter defibrillator received appropriate shocks or successful antitachycardia pacing. Although no patient died suddenly, overall mortality was 17% in this group. It is concluded that d/l sotalol is highly effective in the suppression of sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation. However during a mean follow-up of 27 +/- 12 months a recurrence of ventricular tachycardia was seen in 21% of patients, and one patient died suddenly.