Effects of verapamil on left ventricular diastolic dysfunction

To assess the effects of verapamil on left ventricular relaxation and filling dynamics in patients with left ventricular diastolic dysfunction (LVDD), Doppler echocardiography (DE) and cardiac catheterization (Cath) were simultaneously performed in 30 cases with LVDD. The left ventricular filling and relaxation indices were measured with DE and Cath respectively, before and after intravenous injection of verapamil. The result showed that after verapamil injection all left ventricular filling measured with DE were significantly improved in all cases, while left ventricular relaxation indices showed significant improvement only in patients with hypertrophic cardiomyopathy and hypertensive heart disease but no changes in patients with old myocardial infarction. There were no significant correlations between left ventricular filling and relaxation indices. It is concluded that the major mechanism of left ventricular filling improvement induced by verapamil is the reduction of left ventricular afterload and verapamil has different therapeutic effects on LVDD with different etiology.     

Pregnancy-induced severe left ventricular systolic dysfunction in a patient with hypertrophic cardiomyopathy

This paper reports the first case of hypertrophic cardiomyopathy (HCM) that developed postpartum congestive heart failure (CHF) and severe left ventricular (LV) systolic dysfunction. Review of the literature and clinical implications are discussed.     

Parasympathetic neuropathy associated with left ventricular diastolic dysfunction in patients with insulin-dependent diabetes mellitus

BACKGROUND: As extracorporeal shock wave lithotripsy (ESWL) is frequently carried out on an outpatient basis, it is crucial to choose an adequate analgesic with less adverse effect. This study evaluated the use of three different intravenous agents: fentanyl, tramadol HCl and tenoxicam in ESWL. METHODS: One hundred and twenty patients undergoing lithotripsy were randomly assigned to receive either intravenous fentanyl 1 microgram/kg, tramadol HCl 1.5 mg/kg or tenoxicam 0.3 mg/kg before lithotripsy. Pain intensity was recorded using verbal rating pain scales (VRPS). Cases without adequate analgesia (VRPS > 4) or could not tolerate the pain, additional bolus of fentanyl 25 micrograms were given until adequate analgesia was achieved. Side effects were recorded as well. RESULTS: No significant differences were found among groups in demographic data, VRPS, number of total shock waves, cases with supplementary fentanyl, mean dose of supplementary fentanyl or the incidence of dizziness. However, the incidence of nausea or vomiting was significantly higher in fentanyl and tramadol groups comparing with tenoxicam group (15.0% and 25.0% vs. 0.0%). Oxygen saturation in fentanyl group was also significantly lower than the other two groups (p < 0.01). In addition, VRPS had a significant correlation with voltage intensities (p < 0.05). CONCLUSIONS: Lithotripsy can be satisfactorily performed by employing fentanyl, tramadol or tenoxicam for analgesia; tenoxicam apparently offers a better analgesic quality with less side effect. Furthermore, the need for stronger analgesia during larger voltage intensity should be tailored to the needs of the individuals.     

Effects of felodipine on left ventricular systolic and diastolic performance in congestive heart failure

We studied the effects of a dihydropyridine calcium blocker, felodipine, on left ventricular (LV) contractile performance and diastolic filling dynamics in conscious dogs with pacing-induced congestive heart failure (CHF) before and after autonomic blockade. Eleven conscious dogs were instrumented to measure micromanometer LV and left atrial (LA) pressure (P) and to determine LV volume (V) from three dimensions. CHF was induced by 4 to 5 weeks of right ventricular pacing. After CHF, the mean LV end-diastolic (ED) P increased (9.7 +/- 2.9 vs. 27.9 +/- 6.8 mm Hg, P < .05), LVEDV and end-systolic (ES) V increased and stroke volume (SV) decreased (15.3 +/- 2.4 vs. 9.6 +/- 3.0 ml, P < .05). The time constant of LV relaxation (T) (25.9 +/- 2.9 vs. 37.9 +/- 5.1 msec, P < .05) and LVES wall stress (WS) (63.4 +/- 21.0 vs. 74.6 +/- 23.7 g/cm2, P < .05) also increased. After CHF, felodipine (25 nmol/kg i.v., plasma concentrations 17.4 +/- 3.2 nmol/L) produced significant decreases in LVESP (119 +/- 12 vs. 96 +/- 11 mm Hg, P < .05), arterial elastance, total systolic resistance (TSR) (0.11 +/- 0.04 vs. 0.07 +/- 0.03 mm Hg/ml/min, P < .05) and LVESWS (74.6 +/- 23.7 vs. 60.2 +/- 17.3 g/cm2, P < .05). Felodipine increased the slopes of the ESP-V relation (5.6 +/- 1.5 vs. 7.8 +/- 0.7 mm Hg/ml, P < .05), the dP/dtmax-EDV relation (51.4 +/- 6.1 vs. 85.3 +/- 10.1 mm Hg/ml sec, P < .05) and the stroke work-EDV relation (69.8 +/- 7.1 vs. 78.9 +/- 7.1 mm Hg, P < .05) and shifted all three relations to the left, indicating enhanced contractile performance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy

Atrial and brain natriuretic peptides (ANP and BNP) are produced by the heart, and their plasma concentrations are increased in human chronic congestive heart failure. Although separate studies have suggested that circulating levels of the biologically active C-terminal ANP, the biologically inactive N-terminal ANP, and BNP may have diagnostic utility in the detection of left ventricular systolic dysfunction or left ventricular hypertrophy, no studies have directly assessed the relative value of these peptides prospectively. We therefore designed this study to compare the relative ability of the different natriuretic peptides to detect abnormal left ventricular systolic and diastolic function and left ventricular hypertrophy. Using a prospective study design, we investigated 94 patients referred for cardiac catheterization and 15 age-matched normal subjects. The diagnostic abilities of elevated plasma C-terminal ANP, N-terminal ANP-(1-30), and BNP concentrations to identify systolic dysfunction (ejection fraction < 45%), diastolic dysfunction (time constant of left ventricular relaxation > 55 milliseconds, left ventricular end-diastolic pressure > 18 mm Hg), and left ventricular hypertrophy (left ventricular mass index > 120 g/m2) were objectively compared by receiver operating characteristic analysis. The areas under the receiver operating characteristic curve of BNP for detecting each of these abnormalities ranged from 0.715 to 0.908 and were significantly greater than those of C-terminal ANP or N-terminal ANP-(1-30). The sensitivity and specificity of an elevated plasma BNP, which we defined as greater than the mean + 3 SD of the 15 age-matched normal subjects, were 0.83 and 0.77, respectively, for detecting ejection fraction less than 45%, 0.85 and 0.70 for detecting the time constant of left ventricular relaxation greater than 55 milliseconds, 0.63 and 0.76 for detecting left ventricular end-diastolic pressure greater than 18 mm Hg, and 0.81 and 0.85 for detecting left ventricular mass index greater than 120 g/m2. The use of BNP and one other peptide increased sensitivity (0.90 to 0.96), albeit with lower specificity (0.56 to 0.71). An elevated plasma BNP was a more powerful marker of left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and left ventricular hypertrophy than C-terminal ANP or N-terminal ANP-(1-30) in this population of patients with suspected cardiac disease. Measurement of BNP alone or in combination with C-terminal ANP or N-terminal ANP-(1-30) has potential utility for the detection of altered left ventricular structure and function in a patient population at risk for cardiovascular disease.     

Reduced systemic arterial compliance is associated with left ventricular hypertrophy and diastolic dysfunction in older people

OBJECTIVES: To study the relationship between left ventricular diastolic function and systemic arterial compliance in the older population. DESIGN: Cross-sectional survey. PARTICIPANTS: A total of 67 older volunteer participants (aged 67 +/- 5.4 years). MEASUREMENTS: Systemic arterial compliance (SAC) was measured using applanation tonometry and aortic velocimetry, and diastolic function was assessed using Doppler filling. Left ventricular mass was determined echocardiographically. RESULTS: There were significant univariate correlations between diastolic filling, as measured by E/A ratio, systemic arterial compliance (0.34, P < .01), and left ventricular mass (-0.41, P < .001). In multiple regression analysis, using diastolic filling as the dependent variable and heart rate, age, left ventricular mass corrected for body surface area, systolic and diastolic blood pressures, and arterial compliance as independent variables, the major determinants of diastolic filling were heart rate, left ventricular mass, and diastolic blood pressure. Arterial compliance did not make a significant independent contribution. CONCLUSION: This study demonstrates a positive relationship between diastolic filling and arterial compliance in the older population. However, in multiple regression analysis, heart rate, diastolic blood pressure, and left ventricular mass were the independent predictors of diastolic filling (E/A), whereas arterial compliance was not. These findings imply that therapeutic modulation of aortic stiffness would not, of itself, contribute to improvement in diastolic function.     

One year of exercise training does not alter resting left ventricular systolic or diastolic function

This study tested the effects of light schedules on performance and yields of broiler chickens. In Experiment 1, light treatments during Days 1 to 49 of age were: 1) 23 h light (L):1 h dark (D); 2) 16L:8D;3) 16L: 3D:1L:4D; and 4) 16L:2D:1L:2D:1L:2D. In Experiment 2, Light Treatments 1 and 2 were the same as Treatments 1 and 4, respectively, in Experiment 1; 3) 23L:1D Days 1 to 7, 16L:8D Days 8 to 14, the light period was increased by 2 h/wk during Days 15 to 35, and 23L:1D Days 36 to 42; and 4) 23L:1D Days 1 to 7, 16L:8D Days 8 to 14, 16L:3D: 2L:3D Days 15 to 21, 16L:2D:4L:2D Days 22 to 28, 16L: 1D:6L:1D Days 29 to 35, and 23L:1D thereafter. In Experiment 1, BW was greater in Treatment 4 than Treatment 2 at 22 (708 vs 642 g) and 49 d (2,948 vs 2,797 g), percentage leg problems was lower in Treatments 2 to 4 (9, 10 and 6%, respectively) than in Treatment 1 (20%), and percentage Grade A was greater in Treatment 4 than Treatment 2 (60 vs 46%) at 49 d. In Experiment 2, BW was greater in Treatment 1 (692 g) than Treatments 3 (617 g) and 4 (620 g) at 21 d, and the incidence of tibial dyschondroplasia was lower in Treatment 2 (3.1%) than Treatment 3 (15.3%) at 42 d. There were no differences for mortality among treatments in either experiment.     

Transient normalization of systolic and diastolic function after support with a left ventricular assist device in a patient with dilated cardiomyopathy

A 19-year-old man who had fulminant heart failure caused by an idiopathic dilated cardiomyopathy was supported with a left ventricular assist device for 183 days as a bridge to heart transplantation. At the time of intended transplantation it was noted that the patient's heart had returned to normal size, had a normal ejection fraction, and was able to maintain normal pressures and flows. In view of the apparent recovery of cardiac properties, the left ventricular assist device was explanted and the transplantation was not performed. However, the heart dilated, ejection fraction worsened, and the patient died of heart failure exacerbated acutely by a systemic viral illness. Although such recovery of systolic function is uncommon, as use of the left ventricular assist devices becomes more widespread other physicians might encounter similar findings and, in this regard, they might find our experience useful as they contemplate their treatment options.     

Is the treatment of left ventricular systolic dysfunction different according to the etiology?

Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an alpha-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNF alpha release.     

Effect of gender and left ventricular dysfunction on the incidence of hypotension induced by dobutamine stress echocardiography

BACKGROUND: Of patients who undergo dobutamine stress echocardiography (DSE), 14% to 38% experience hypotension that sometimes requires termination of the test before an adequate cardiac work-load is reached. The mechanisms of hypotension reportedly are related to peripheral vasodilation, a decrease in cardiac output, and left ventricular (LV) cavity obliteration. DSE is performed increasingly in women and in patients with LV dysfunction. However, the impact of gender and LV dysfunction on DSE-induced hypotension has not been elucidated. METHODS AND RESULTS: Clinical, hemodynamic, and echocardiographic characteristics were studied in 412 patients undergoing DSE, 82 patients with an LV ejection fraction of 40% or less, and 147 women. Hypotension, defined as a decrease in systolic blood pressure of at least 20 mm Hg, occurred in 117 (28%) patients. Hypotension was more common in women than men (36% vs 24%, P = .01). Hypotension was also more common in older adults (P = .004), persons taking diuretics (P = .025) or angiotensin-converting enzyme inhibitors (P = .01), and persons with higher baseline blood pressures (P < .0001). Hypotension was not related to the use of beta blockers, calcium channel blockers, digoxin, nitrates, LV dimensions, or ejection fraction. CONCLUSIONS: The incidence of DSE-induced hypotension is related to gender but not to the level of LV systolic function. It also is associated significantly with higher age, and use of angiotensin-converting enzyme inhibitors or diuretics.     

Coronary arterial anatomy in patients with left ventricular systolic dysfunction without chest pain or previous myocardial infarction

Patients with left ventricular systolic dysfunction without chest pain or previous myocardial infarction are unlikely to have 3-vessel coronary artery disease and are very unlikely to have coronary anatomy suitable for bypass grafting. Of our 108 subjects, only 3 (3%) had 3-vessel coronary artery disease thought to be suitable for revascularization.     

Impact of ambulatory blood pressure on left ventricular diastolic dysfunction in uncomplicated arterial systemic hypertension

To determine the relations of 24-hour blood pressure (BP) and its different phases with left ventricular (LV) diastolic filling, 125 subjects (mean age 46 years) not taking cardiac drugs were studied by Doppler echocardiography and ambulatory BP recording. Subjects (excluding those with coronary artery or valvular heart disease, heart failure, or diabetes) were classified into 2 groups according to the level of Doppler-derived ratio of peak early to atrial velocity (E/A ratio): 59 had E/A >1 (normal diastole), 62 had E/A <1 (impaired diastole), and 4 had E/A = 1. Patients with E/A <1 were older and had higher LV mass indexed for height, average 24-hour BP, average nighttime BP, and lower day-night BP decrease, whereas average daytime BP did not differ significantly between the 2 groups. Negative correlations of E/A were found with age, heart rate, office, average 24-hour and average nighttime systolic and diastolic BP, and LV mass index. In a multivariate model that included potentially confounding factors, only age (standardized beta coefficient = -0.52, p<0.00001), nighttime BP (beta = -0.28, p<0.0001), and heart rate (beta = -0.22, p<0.001) were independent predictors of E/A in the pooled population. In conclusion, LV diastolic function is more closely related to ambulatory, rather than to clinic, BP measurements, and high average nocturnal diastolic BP is a powerful marker of LV filling impairment.     

Midwall fractional shortening is an independent predictor of left ventricular diastolic dysfunction in asymptomatic patients with systemic hypertension

Conventional measures of left ventricular (LV) systolic performance suggest that diastolic dysfunction precedes the development of systolic dysfunction in hypertension. Midwall fractional shortening is a new measure of systolic function that identifies hypertensive patients who have evidence of target-organ damage, impaired contractile reserve, and increased mortality. We therefore sought to determine whether depressed midwall fiber shortening is associated with abnormal diastolic function. Echocardiograms were obtained in 102 otherwise healthy hypertensive patients without treatment with normal conventional measures of systolic function. Of these, 15 had depressed midwall shortening based on previously described normative relations. Patients with depressed midwall shortening had slightly higher blood pressure. Abnormal diastolic function, defined as late (A) LV inflow velocity greater than early (E) velocity, was observed in 33% of those with normal midwall shortening but in 60% of those with depressed shortening (p <0.05). Patients with A/E >1 had lower absolute midwall fiber shortening (15 +/- 3% vs 18 +/- 3%, p <0.0001) but similar endocardial shortening. Patients with abnormal midwall shortening had higher A/E and longer isovolumic relaxation times (both p <0.05). In multivariate analysis, midwall fractional shortening, age, and heart rate were independent predictors (p <0.01) of A/E in a model including blood pressure, LV mass, and endocardial shortening. We conclude that subnormal midwall shortening predicts LV diastolic abnormalities in this population of hypertensive patients with otherwise normal measures of LV systolic function. Contrary to our previous understanding, depressed LV systolic performance, when identified with this newer method, occurs coincidentally with impaired diastolic function.     

Right ventricular diastolic disfunction and its relation to left ventricular performance in patients with hypertension

The potential effects of propofol emulsion (Diprivan) on the neuromuscular transmission and muscular contraction were studied using in vitro and in vivo nerve-muscle preparations of rats. The contractions of the isolated rat diaphragm elicited by either indirect or direct electrical stimulation were inhibited by propofol emulsion at threshold concentrations of 42 and 112 mumol l-1, respectively. Similarly, the gastrocnemius muscle contractions induced by either indirect or direct electrical stimulation in vivo were inhibited by propofol emulsion administration as a bolus injection of 2.5 mg kg-1 intravenously, followed by intravenous infusion of 150 micrograms kg-1 min-1 for 1 h into rats. The inhibitory effects of propofol in both preparations were greater with indirect rather than direct stimulation. Propofol emulsion was found to be capable of enhancing the paralysis of the indirectly stimulated rat diaphragm in vitro and gastrocnemius muscle in vivo induced by either pipecuronium or succinylcholine. The combination of propofol and pipecuronium led to a synergistic inhibition of the neuromuscular transmission, while the combination of propofol and succinylcholine led to additive inhibition. Pretreatment with propofol emulsion at these threshold concentrations markedly inhibited the stimulant effects of aminophylline and digoxin on the indirectly and directly induced diaphragmatic contractions. Also, the enhancement effects of aminophylline on the indirectly and directly and of digoxin on indirectly induced rat gastrocnemius muscle contractions were markedly inhibited by propofol emulsion administration to rats. Pretreatment with propofol emulsion at the threshold concentrations enhanced the inhibitory effects of verapamil on diaphragmatic contractions elicited either indirectly or directly and enhanced the inhibitory effect of adenosine on the contractions elicited indirectly. Similarly, the inhibitory effects of verapamil on the indirectly and directly and of adenosine on indirectly induced rat gastrocnemius muscle contractions were markedly potentiated by propofol emulsion administration to rats. In addition, doubling the concentration of calcium in the bathing fluid produced no change in the inhibitory effects of propofol emulsion on either indirectly or directly elicited diaphragmatic contractions, while doubling the concentration of external magnesium potentiated the propofol effects. Pretreatment with 4-aminopyridine suppressed the inhibitory effects of propofol emulsion on diaphragmatic contractions elicited either indirectly or directly. These results suggest that propofol acts presynaptically to inhibit the neuromuscular transmission and acts at the muscle membrane to inhibit the muscular contraction.     

Use of pulsed Doppler tissue imaging to assess regional left ventricular diastolic dysfunction in hypertrophic cardiomyopathy

In this study, regional diastolic patterns and their relations with transmitral Doppler inflow were investigated in hypertrophic cardiomyopathy (HC) by pulsed Doppler tissue imaging (DTI). Doppler echocardiography and DTI of basal septum and lateral wall (apical 4-chamber view) were performed in 20 patients (15 men and 5 women) with HC and in 10 healthy subjects (7 men and 3 women). Diabetes, hypertension, coronary artery and valvular disease, mitral regurgitation, New York Heart Association functional classes III to IV, sinus tachycardia, atrial fibrillation, and inadequate echocardiograms were exclusion criteria. Peak velocity and time-velocity integral of early and late waves and their ratios, and deceleration and isovolumic relaxation times were determined by standard Doppler and by DTI at the septal and lateral wall levels. The 2 groups were comparable for age, heart rate, blood pressure, and ejection fraction. Transmitral peak velocity and time-velocity integral E/A ratios were reduced (both p <0.05) and deceleration and isovolumic relaxation times prolonged (both p <0.00001) in HC. Septal DTI showed lower peak velocity and time-velocity integral e/a ratios (p <0.00001 and p <0.001, respectively) and lengthened regional deceleration (p <0.01) and isovolumic (p <0.001) relaxation times. DTI of the lateral wall showed a prolongation of deceleration and isovolumic relaxation times (both p <0.01). By dividing HC according to transmitral E/A, 8 patients with E/A <1 had lower DTI septal e/a ratio (p <0.01) and prolonged septal deceleration and isovolumic relaxation times (both p <0.01) but no changes in DTI pattern of lateral wall than 12 patients with E/A > 1. In conclusion, DTI is useful and complementary to standard Doppler imaging to characterize diastolic properties in HC, reflecting a typical pattern of intramyocardial impaired relaxation at the level of hypertrophied septum and also providing information about the degree of this regional impairment. The lateral wall presents minor changes in diastolic times, which indicate how diastolic asynchrony is not confined to the hypertrophied segment in HC.     

Reversible left atrial dysfunction possibly due to afterload mismatch in patients with left ventricular dysfunction

OBJECTIVE: The aim of this study was to define the clinical-therapeutical approach to endometrial cancer now being followed in some of the most important centers of reference for gynecological cancer in North America by means of a questionnaire. STUDY DESIGN: The questionnaire focused on four principal areas: (1) surgical staging and therapy; (2) adjuvant treatment; (3) treatment modifications; and (4) management of advanced stages (FIGO III-IV). RESULTS: There were 48 evaluable responses (77%) received by the end of December 1994 which were considered for this analysis. Lymphadenectomy is utilized routinely in 26/48 centers (54.2%) and in selective clinical-pathological conditions in another 21/48 centers (43.5%). In the majority of centers (31/48; 64.6%) radical surgery is utilized for selected indications such as cervical involvement. Only 3/48 (6.2%) centers consider the vaginal approach totally inappropriate. The great majority (40/48; 83.3%) of the centers considered postsurgical adjuvant therapy to be necessary in FIGO Stage Ic. Brachytherapy is routinely performed in 3 centers (6.2%) in postsurgical management of Stage I endometrial cancer, while the majority of the centers (31/48; 64.6%) perform brachytherapy of the vaginal vault in certain clinical-pathological conditions. A wide variety of treatments are used for advanced stages (FIGO III-IV). CONCLUSIONS: It emerges that some controversial aspects exist on endometrial cancer treatment, and these conflicting data need a large-scale multicenter randomized clinical trial.     

Optimal control evaluation of left ventricular systolic dynamics

A model of the contracting left ventricle was developed, in which the left ventricle was represented as a time-varying compliance. The vascular load included the nonlinear (Bernoulli) resistance of the aortic valve, blood inertance, and a Windkessel model of the arterial tree. Owing to the obligatory aerobic nature of the heart, oxygen consumption can be used to characterize the energy utilized by the myocardium. An adaptive control law was developed for determining the systolic time course of ventricular pressure and volume that minimizes cardiac oxygen consumption. Three main determinants of myocardial oxygen consumption were included in the integral criterion function: developed wall tension, inotropic state, and external (mechanical) work. The optimal control problem was solved using the Pontryagin maximum principle. The model could predict, in good agreement with experimentally obtained data, systolic time course of ventricular pressure and volume, as well as directional changes in the duration of isovolumic contraction and ejection phase under various conditions of end-diastolic volume, mean aortic pressure, and inotropic state.