Steps forward in the assessment of myocardial viability in left ventricular dysfunction

Molecular chaperones protect proteins against environmental and physiologic stress and from the deleterious consequences of an imbalance in protein homeostasis. Many of these stresses, if prolonged, result in defective development and pathologies associated with a diverse array of diseases due to tissue injury and repair including stroke, myocardial reperfusion damage, ischemia, cancer, amyloidosis, and other neurodegenerative diseases. We discuss the molecular nature of the stress signals, the mechanisms that underlie activation of the heat shock response, the role of heat shock proteins as cytoprotective molecules, and strategies for pharmacologically active molecules as regulators of the heat shock response.     

Right and left ventricular dysfunction in patients with severe pulmonary disease

AIM OF STUDY: To measure the effect of specific preoperative information on postoperative anxiety, satisfaction with information, and demand for analgesia, of Chinese males having transurethral resection of the prostate (TURP). DESIGN: A controlled experimental design. The researchers allocated all patients (n = 30) undergoing TURP in a general hospital in Hong Kong, during a 3-month period, to one of two groups. The experimental group (n = 15) received a specific information pamphlet and a general preoperative counselling video. The control group (n = 15) received a video alone. PROCEDURE AND MEASURES: Following ethical approval, a researcher took baseline measures of state and trait anxiety using the Chinese State-Trait Anxiety Inventory (C -STAI). Five days after surgery the researcher administered the C-STAI (A-State), a patients' satisfaction questionnaire, and, recorded requests for analgesia during the first 5 postoperative days. RESULTS: Experimental subjects reported significantly lower anxiety levels post-operatively and a significantly higher level of satisfaction with the preoperative information, than controls. Postoperative demand for analgesia did not significantly differ between groups. CONCLUSIONS: The findings support the importance of providing patients with specific, written preoperative information about their surgery and its effects to minimize their postoperative anxiety levels, and improve their satisfaction with the care provided.     

ECG-gated dual-isotope myocardial SPECT with 201Tl and 99mTc-tetrofosmin: simultaneous assessment of stress/rest myocardial perfusion and left ventricular function

ECG-gated dual-isotope acquisition protocol involving rest imaging with 201Tl and stress 99mTc-tetrofosmin (TF) SPECT was designed for the simultaneous assessment of rest/stress myocardial perfusion and rest ventricular systolic function. This study assessed the feasibility and diagnostic accuracy of this protocol. Forty-five patients underwent the dual-isotope SPECT protocol. Twenty minutes after resting injection of 111 MBq of 201Tl, 370 MBq of 99mTc-TF was administered at a peak exercise. The dual-isotope gated SPECT acquisition was performed 1 hour later. Then, the regional count increase rate (%WT) of 99mTc-TF from end-diastole end-systole was calculated using an automated method which was developed for quantification of regional wall thickening based on circumferential profile analysis in our laboratory. Myocardial perfusion and contractility analysis was carried out using 8 segments of left ventricle with comparison of coronary angiographical findings. The sensitivity and specificity for the detection of diseased coronary vessels (> = or 75% stenosis) were 76% and 94%, respectively. Infarcted regions showing reversible defect had significantly greater %WT as compared with those with fixed defects (63 seg; 12.7 +/- 6.1% vs. 36 seg; 8.9 +/- 7.2%, p < 0.01). In conclusion, this dual-isotope protocol has some advantages; i.e., shortening an examination time, having the exact registration of stress/rest perfusion, and simultaneous evaluation of resting regional wall thickening.     

Contrast magnetic resonance imaging in the assessment of myocardial viability in patients with stable coronary artery disease and left ventricular dysfunction

BACKGROUND: The utility of contrast MRI for assessing myocardial viability in stable coronary artery disease (CAD) with left ventricular dysfunction is uncertain. We therefore performed cine and contrast MRI in 24 stable patients with CAD and regional contractile abnormalities and compared MRI findings with rest-redistribution 201Tl imaging and dobutamine echocardiography. METHODS AND RESULTS: Delayed MRI contrast enhancement patterns were examined from 3 to 15 minutes after injection of 0.1 mmol/kg IV gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Comparable MRI and 201Tl basal and midventricular short-axis images were subdivided into 6 segments. Segments judged nonviable by quantitative and qualitative assessment of 201Tl scans showed persistent, systematically greater MRI contrast signal intensity than segments judged viable (P相似文献   

Safety and utility of atropine addition during dobutamine stress echocardiography for the assessment of viable myocardium in patients with severe left ventricular dysfunction

OBJECTIVE: To assess the feasibility safety and side effects of the addition of atropine to dobutamine stress echocardiography for the detection of viable myocardium in patients with left ventricular dysfunction (ejection fraction < or = 35%) prior to coronary revascularization. BACKGROUND: The assessment of viable and/or ischaemic myocardium has high prognostic value as regards improvement of function and survival after coronary revascularization. The addition of atropine to dobutamine during echocardiographic testing for the presence of viable myocardium is not common practice. Consequently, no data exist on the safety and additional diagnostic value of this practice. METHODS: Two hundred patients with left ventricular ejection fraction < or = 35% were studied. RESULTS: Test end-points were: target heart rate in 164 (82%) of the patients, severe angina in 18 (9%), maximum dobutamine-atropine dose in six (3%), severe ST segment changes in five (2%), cardiac arrhythmias in four (2%), and hypotension in three (1%). Viability could be assessed echocardiogaphically in 105/200 (53%) from a biphasic response (improvement of wall motion with low dose dobutamine and worsening with high dose), in 93 from ischaemia and in 12 from sustained or late improvements. In 36/105 (34%) patients, ischaemic myocardium could only be assessed after the addition of atropine. Cardiac arrhythmias occurred in 11/200 (6%) and hypotension (decrease of systolic blood pressure >30 mmHg) in 21/200 (11%). Neither the use of atropine nor the induction of ischaemia were associated with an increased incidence of cardiac arrhythmias or hypotension. CONCLUSIONS: In a large group of patients with severe left ventricular dysfunction, dobutamine stress echocardiography is feasible and safe in 186/200 (93%); the addition of atropine was necessary in 34% to assess myocardial viability. Hypotension and cardiac arrhythmias were the most frequent side effects, but were not related to the induction of ischaemia or addition of atropine.     

Myocardial revascularization in the patient with severe left ventricular dysfunction

In the past, poor ventricular function was considered a contraindication for myocardial revascularization. More recently, however, patients once considered to be a prohibitive risk for coronary artery bypass procedures are undergoing surgery with acceptable operative mortality and successful long-term outcomes. In fact, reparative surgical results often exceed those achieved through medical management and/or transplantation.     

Acute myocardial infarct and left ventricular dysfunction. Morphologic bases, clinical aspects and pharmacologic prevention

The morphological bases which condition left ventricular disfunction after acute myocardial infarction as well as the concepts of expansion and remodelling of the myocardium are reviewed. The clinical aspects indicating ventricular disfunction are presented and several pharmacological effects which have been proposed for the prevention of this situation. Particular emphasis is given to the role of angiotensin-converting enzyme inhibitors in the prevention of left ventricular disfunction after acute myocardial infarctions, based on the most recent clinical trials.     

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.     

Dobutamine-atropine stress echocardiography for risk stratification in patients with chronic left ventricular dysfunction

OBJECTIVE: To assess the prognostic value of sustained improvement, scar and inducible ischemia with or without viability in patients with chronic left ventricular dysfunction (LVD). BACKGROUND: Dobutamine-atropine stress echocardiography (DASE) accurately detects scar, reversible dysfunction and the extent of coronary artery disease in LVD. METHODS: Three hundred fifty consecutive patients (age 62+/-13 years, mean+/-SD, 215 men/135 women) with moderate to severe LVD (LVEF < 40%, mean 30+/-8%) underwent DASE and were followed for > or =18 months. Dobutamine-atropine stress echocardiographic findings were classified according to sustained improvement in all vascular territories, scar, inducible ischemia (worsening wall motion at peak dose only or biphasic responses) and their extent. RESULTS: Sustained improvement occurred in 83 patients (24%), scar alone in 99 (28%) and inducible ischemia in 168 (48%, with biphasic responses in 104). Ischemia was induced in all vascular territories in 26 patients. Patients with sustained improvement or scar alone were treated medically, whereas 46% (78/168) with inducible ischemia were revascularized (coronary bypass surgery, n = 67 or angioplasty, n = 11). There were 76 hard events including cardiac death in 59, nonfatal myocardial infarction in 11, and resuscitated sudden death in 6. Hard events were rare in sustained improvement (5%, 4/83), uncommon in scar (13%, 13/99) and common (p < 0.01) in medically treated patients with inducible ischemia (59%, 53/90). Cardiac deaths were especially common (p < 0.01) in patients with biphasic responses (55%, 28/51). Inducible ischemia independently predicted hard events (chi2 = 75.35, p < 0.001) along with reduced LVEF at peak dose (chi2 = 8.38, p = 0.004). Hard cardiac events were uncommon (8%, 6/78, p < 0.001) in patients with inducible ischemia who underwent early revascularization. CONCLUSIONS: Inducible ischemia during DASE was the major determinant of outcome in LVD and independent of clinical data and left ventricular function. Improved wall thickening alone and scar alone predicted good outcome. Survival of patients with inducible ischemia was better after revascularization.     

Relation between left ventricular function and oxidative stress in patients undergoing bypass surgery

OBJECTIVE: To determine whether preoperative left ventricular ejection fraction (LVEF) is related to the degree of myocardial oxidative stress during bypass surgery in man. DESIGN: Observational study. SETTING: Tertiary care centre. PATIENTS AND INTERVENTIONS: 31 patients (LVEF range was 20% to 68%) undergoing elective coronary bypass surgery with blood cardioplegic reperfusion were studied. Arterial and coronary sinus blood was collected before aortic cross clamping (T0) and at 0 (T1), 15 (T2), and 30 (T3) minutes after unclamping. Transmural left ventricular biopsies were also obtained from 15 patients at T0 and at T1. MAIN OUTCOME MEASURES: Glutathione and adenine nucleotides were measured in myocardial biopsies, while coronary sinus-artery differences for glutathione, nucleotides, and products of lipid peroxidation were calculated from blood specimens. Creatine kinase (myocardial band; CK-MB) was measured in plasma at four and 12 hours after operation. RESULTS: Myocardial glutathione and adenine nucleotides were correlated (p < 0.02) with preoperative LVEF both at T0 (r = 0.909 and 0.672) and T1 (r = 0.603 and 0.605). Oxidised glutathione released from the heart during reperfusion was inversely correlated with LVEF (r = -0.448, -0.466, and -0461 at T1, T2, and T3, p < 0.01), while reduced glutathione (r = 0.519 and 0.640 at T1 and T2) and glutathione redox ratio (r = 0.647, 0.714, 0.645, and 0.702 at T0, T1, T2, and T3) showed a direct correlation (p < 0.01). Lipid peroxidation at T1 was negatively related to LVEF (r = -0.492). CK-MB was also negatively related to LVEF (r = -0.440 at 4 h and -0.462 at 12 h). CONCLUSIONS: The capacity to counterbalance oxidative burst following ischaemia and reperfusion appears to be related to the functional ability of the heart.     

Abnormal coronary flow dynamics at rest and during tachycardia associated with impaired left ventricular relaxation in humans: implication for tachycardia-induced myocardial ischemia

OBJECTIVES: This study attempted to clarify the effect of ventricular relaxation abnormalities on coronary flow dynamics at rest and during tachycardia in humans. BACKGROUND: Ventricular relaxation abnormality has been demonstrated in animals to have an adverse impact on early diastolic coronary flow dynamics. However, this relation has not been established in humans. Even if the adverse effect were latent at rest, it might become evident during tachycardia because tachycardia reduces coronary flow reserve and facilitates the production of myocardial ischemia. METHODS: Doppler phasic left coronary flow velocity pattern was obtained at rest and during tachycardia in 23 patients without coronary stenosis. The time constant of left ventricular isovolumic pressure (tau) was used to assess ventricular relaxation. RESULTS: The time to peak flow velocity of the diastolic coronary flow wave was longer, and the fraction of the first third of diastolic coronary flow was smaller, in patients with a longer tau (r = 0.58, p < 0.01; r = -0.44, p < 0.05), indicating a close relation between early diastolic coronary flow dynamics and ventricular relaxation. Although rapid atrial pacing yielded an increase in the coronary flow velocity integral per minute in all patients, diastolic coronary flow velocity integral per minute increased in 9 patients with a normal (< or = 40 ms) tau at rest but decreased in 14 patients with a longer (> 40 ms) tau at rest. CONCLUSIONS: Impaired left ventricular relaxation was associated with decreased coronary flow in early diastole at rest and decreased coronary flow throughout diastole during tachycardia in patients without coronary stenosis. These findings may provide more insight into the mechanism of tachycardia-induced subendocardial ischemia in patients with impaired ventricular relaxation but without concomitant coronary stenosis.     

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.     

Importance of intrinsic calf vasodilator capacity in determining distribution of skeletal muscle perfusion during supine bicycle exercise in patients with left ventricular dysfunction

Although there is interest in forming synthetic analogs of hard tissues at physiologic temperature, significant gaps in knowledge exist with respect to the mechanisms by which precursor solids convert to apatites and also with respect to the apatite compositions that may be formed. In this study calcium-deficient HAp [Ca9(HPO4)(PO4)5OH] was prepared by hydrolysis of tricalcium phosphate (TCP), alpha-Ca3(PO4)2. The kinetics of HAp formation were studied as a function of temperature by isothermal calorimetry. TCP hydrolyzed completely within about 12 h, and the hydrolysis reaction evolved 133 kJ/mol of HAp formed. Although the kinetics of hydrolysis exhibited a strong temperature dependence, the mechanistic path taken appeared independent of temperature. The fluoridation of hydroxyapatite compositions having Ca/P ratios higher than 1.59 previously has been investigated. However, little work has been done on the fluoridation of more calcium-deficient hydroxyapatite. Ca9(HPO4)(PO4)5OH was formed at temperatures between 37.4 degrees and 55 degrees C to vary its morphology. These preparations then were reacted in NaF solution and the kinetics of fluoride incorporation studied. Solution chemical analyses were used to determine the amounts of fluoride incorporated. The extent of hydroxyl replacement by fluoride ranged from 17 to 72% and correlated with the surface area of the parent HAp.     

Characteristics of patients hospitalized for myocardial infarction in France with respect to left ventricular dysfunction. Results of the USIK study

Patients admitted in coronary care units, in november 1995, for confirmed acute myocardial infarction within 48 hours of symptoms onset were included in this study. The choice of measurement of left ventricular ejection fraction (LVEF) was left to the physician in charge. Only investigations performed within the first 8 days were taken into consideration. In cases with multiple investigations, the following order of preference was applied: a) angiographic LVEF, b) isotopic LVEF, c) echocardiographic ejection fraction by Simpson's method, d) echocardiographic ejection fraction by Berning's method, e) semi-quantitative visual echocardiographic evaluation. 2563 patients were included (1827 males and 736 females, mean age 67 years). A quantitative evaluation of LVEF was obtained in 1477 patients (57%) whereas 2 053 patients (80%) underwent at least a semi-quantitative evaluation. The average LVEF was 50% and 17% of patients had an ejection fraction < or = 35%. Patients with LVEF < or = 35% were older, less likely males, non smokers and diabetics. Prior heart failure, previous myocardial infarction and anterior location in infarction were more frequent. Heart failure was more frequent in patients with LVEF < or = 35% (75 vs 23%, p < 0.001). One hundred and ninety-seven patients (7.7%) died in the five first days following the onset of symptoms. A left ventricular ejection fraction < or = 35% multiplied the risk of death by 8.1 (Confidence interval: 5.7-11.4, p < 0.001). The presence of clinical heart failure increased the risk even more.     

Diminished contractile reserve in patients with left ventricular hypertrophy and increased end-systolic stress during Dobutamine stress echocardiography

Left ventricular hypertrophy (LVH) is associated with decreased contractile response to inotropic stimulation in animal models, but this has not been documented in humans. To determine whether LVH is associated with decreased myocardial contractile reserve, we measured left ventricular mass, heart rate-corrected velocity of circumferential fiber shortening (Vcfc), end-systolic stress, and LV ejection fraction (LVEF) in patients with LVH and increased end-systolic stress (n = 6) and in patients without LVH (n = 7) who had a normal response to dobutamine stress echocardiography (increased LVEF and no wall motion abnormalities). The afterload-dependent indexes of left ventricular systolic performance were normal at baseline and showed significant increases at peak dobutamine dose (LVH group: Vcfc 0.91 +/- 0.11 to 1.76 +/- 0.59, p = 0.006; LVEF 49 +/- 5 to 65 +/- 6, p = 0.001; group without LVH: Vcfc 1.16 +/- 0.24 to 1.99 +/- 0.36, p = 0.001; LVEF 61 +/- 6 to 68 +/- 6, p = 0.05). The Vcfc/ end-systolic stress relation, a load-independent index of myocardial contractility, rose in a dose-dependent fashion in both groups, but the increment was significantly less for patients with LVH (p < 0.02), suggesting a blunted myocardial contractile reserve to inotropic stimulation. The change in heart rate-corrected velocity of circumferential fiber shortening per unit of change in end-systolic stress in each patient at each dobutamine dose showed a linear and inverse relationship. The increment in heart rate-corrected velocity of circumferential fiber shortening for a given reduction in end-systolic stress was larger in patients without LVH than in patients with LVH (p = 0.01). These results suggest that in patients with LVH and increased end-systolic stress, ventricular performance is maintained at the expense of limited myocardial contractile reserve, and that inotropic stimulation unmasks this abnormality, despite a normal response in LVEF and velocity of circumferential fiber shortening. This approach may identify patients with LVH at risk of developing systolic dysfunction and heart failure.     

Association of calcium channel blocker use with increased rate of acute myocardial infarction in patients with left ventricular dysfunction

The Studies of Left Ventricular Dysfunction (SOLVD) assessed the effect of enalapril in patients with systolic left ventricular dysfunction (LVD). We performed retrospective analyses of the association between calcium channel blocker (CCB) use and fatal and nonfatal myocardial infarction (MI) in these patients. MI occurred in 11.5% of 845 patients receiving CCBs versus 7.5% of 2551 patients not receiving CCBs in the enalapril group and in 14.4% of 874 patients receiving CCBs versus 9.3% of 2527 patients not receiving CCBs in the placebo group. By multivariate Cox regression analysis, adjusting for comorbidity, cause and severity of LVD, heart failure, and concomitant drug use, CCB use was an independent predictor of MI (relative risk [RR] 1.37, confidence interval [CI] 1.14 to 1.63). The increase in MI risk was greater among patients with a higher heart rate (RR 1.46, CI 1.14 to 1.86) and lower blood pressure (RR 1.45, CI 1.14 to 1.86). The adjusted risk ratio for all-cause mortality associated with CCB use was 1.14 (CI 1.00 to 1.28; p = 0.0454). In this analysis of patients with LVD, CCB use was associated with significantly increased risk of fatal or nonfatal MI.     

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.     

Metoprolol abolishes exercise-induced left ventricular dysfunction in patients with silent ischemia

Left ventricular systolic function is reduced during episodes of silent ischemia in patients with coronary artery disease (CAD). Left ventricular ejection fraction (LVEF) is increased at least 5 absolute percent during exercise in most normal subjects; however, in patients with CAD, LVEF often remains unchanged or decreases. The anti-ischemic effect of beta-adrenergic receptor blockade is well documented, including a reduction of exercise-induced electrocardiographic ST depressions; however, the effect of these drugs on left ventricular volume changes during exercise in patients with silent ischemia is unknown. The aim of this study was to evaluate the effect of a cardio-selective beta-blocking agent, metoprolol, on rest and exercise LVEF in patients with silent ischemia, using radionuclide cardiography. Fifteen patients with silent ischemia completed a double-blind, placebo-controlled crossover study at rest and during submaximal exercise. LVEF remained unchanged during exercise in the placebo phase (56% to 58%; p = NS), but even though LVEF tended to decrease 56% during rest after metoprolol versus 52% after placebo (p = NS), the LVEF increase from rest to exercise resembled a normal LVEF response, 52% to 58% (p = 0.005). Exercise-induced electrocardiographic ST depressions were also reduced during metoprolol treatment. In patients with silent ischemia, the exercise-induced change in LVEF rises significantly during metoprolol treatment. The mechanism may be a reduction in myocardial ischemia as indicated by a reduction in ischemic electrocardiographic findings.     

Late survival after valve operation in patients with left ventricular dysfunction

BACKGROUND: Left ventricular dysfunction is a predictor of hospital mortality after cardiac valve operation. We evaluated late survival in a large cohort of these patients. METHODS: From 1980 to 1993, 257 patients with a preoperative ejection fraction of 0.40 or less underwent aortic (n = 177), mitral (n = 72), or combined (n = 8) valve operation, with or without concomitant coronary artery bypass grafting. RESULTS: Hospital mortality was 12.5%. Follow-up was 98% complete. Logistic regression analysis showed that an ejection fraction of less than 0.30, mitral regurgitation, concomitant coronary artery bypass grafting, emergency operation, and reoperation were independent correlates of hospital mortality (all at p < 0.05). Kaplan-Meier survival curves of the 220 hospital survivors showed a 65% 5-year survival. Multivariate analysis revealed preoperative use of diuretics, male sex, reoperation, age exceeding 60 years, and aortic regurgitation to be independent predictors of poor late outcome (all at p < 0.05). CONCLUSIONS: The liability of left ventricular dysfunction with regard to diminished long-term survival is not completely reversed by valve operation. If operation is not performed before left ventricular dysfunction develops, postoperative medical treatment of these dilated, remodeled ventricles should be considered.