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Left ventricular diastolic function: physiology, methods of assessment, and clinical significance.

Diastole, that portion of the cardiac cycle that begins with isovolumic relaxation and ends with mitral valve closure, results in ventricular filling and involves both active (energy-dependent) and passive processes. The interactions between active processes (myocardial relaxation) that primarily influence early ventricular filling and passive processes, such as loading conditions, myocardial compliance, and valvular disease, are complex. Clinical methods to assess ventricular filling include cardiac catheterization, radionuclide angiography, and echocardiography. Any measurements of diastolic function must be made with an understanding of the determinants of ventricular filling and the limitations of the diagnostic test. Many cardiac disorders are characterized by elevated pulmonary venous pressures in the face of normal systolic ventricular function, which suggests a primary abnormality of diastolic function. Abnormalities in diastolic function have been observed in coronary artery disease, congestive heart failure (with and without systolic dysfunction), hypertrophic cardiomyopathy, hypertension, and in healthy elderly subjects. Identification of these abnormalities may be useful clinically, particularly in patients with symptoms of heart failure and normal systolic function. Data are not available to determine the optimal therapy for such patients, although evidence suggests that calcium channel blockers, beta blockers, and agents that reverse myocardial hypertrophy may be useful. This review briefly summarizes the physiology of diastole, the methods of clinical assessment of diastolic function, and the role of diastolic function in cardiovascular disease.

Adult↗

Management of atrial fibrillation in patients with hypertension.

Atrial fibrillation (AF) is a common arrhythmia in patients with hypertensive heart disease. In addition, the presence of hypertension in patients with AF constitutes an important risk factor for the development of thromboembolic events and probably also selects out those individuals who may be resistant to drug therapy. AF in patients with hypertensive heart disease may lead to a number of serious clinical sequelae including stroke, left atrial myopathy, left ventricular dysfunction, and congestive heart failure. This needs to be treated aggressively since many patients may become quite symptomatic when AF develops in the setting of diastolic and systolic dysfunction, regular features of hypertensive heart disease. There are several treatment approaches that may be considered in such patients ranging from interventions to prevent thromboembolic events, drugs and procedures for control of the ventricular response, and drug and non-pharmacologic therapy specifically designed to prevent AF or to restore normal sinus rhythm. This review article will cover each of these components of therapy of AF and will attempt to focus on those therapies that might be best suited for patients with hypertensive heart disease.

Anticoagulants↗

Medical therapy can improve the biological properties of the chronically failing heart. A new era in the treatment of heart failure.

Myocardial failure has been considered to be an irreversible and progressive process characterized by ventricular enlargement, chamber geometric alterations, and diminished pump performance. However, more recent evidence has suggested that certain types of medical therapy may lead to retardation and even reversal of the cardiomyopathic process. In the failing heart, long-term neurohormonal/autocrine-paracrine activation results in abnormalities in myocyte growth, energy production and utilization, calcium flux, and receptor regulation that produce a progressively dysfunctional, mechanically inefficient heart. Interventions such as ACE inhibition and beta-blockade result in a reduction in the harmful long-term consequences of neurohormonal/autocrine-paracrine effects and retard the progression of left ventricular dysfunction or ventricular remodeling. Furthermore, in subjects with idiopathic dilated or ischemic cardiomyopathy, antiadrenergic therapy with beta-blocking agents appears to be able to partially reverse systolic dysfunction and ventricular remodeling. Although the precise mechanisms underlying this latter effect have not yet been elucidated, the general mechanism appears to be via improvement in the biological function of the cardiac myocyte. Such an improvement in the intrinsic defect(s) responsible for myocardial failure will likely translate into important clinical benefits.

Cardiomyopathies↗

Noninvasive estimation of the end systolic pressure-volume relationship using impedance cardiography.

PURPOSE: Traditional measures of cardiac contractility such as dp/dt and ejection fraction has been noted to be sensitive to preload and afterload conditions. The end systolic pressure-volume relationship of the left ventricle (ESPVR, Suga Index or Emax) has been found to be the best load independent measure of the cardiac contractile state. However, determination of the ESPVR requires very highly invasive procedures. Impedance cardiography (IC) is a reliable noninvasive method for calculating stroke volume and may also be useful for estimating the end systolic volume. METHODS: An equation was derived using the systolic time intervals (PEP = pre-ejection period, LVET = left ventricular ejection time) and determined stroke volume (SV) as calculated from the impedance cardiograph to estimate the end systolic volume of the left ventricle. Likewise, and systolic pressure (ESP) was estimated from brachial cuff pressures using a previously published method. The resulting ESPVR was then calculated from tracings recorded in healthy normal subjects and compared to those obtained from patients in decompensated congestive heart failure (ejection fraction < 30% by echocardiogram) using the standard t test (p < 0.05). RESULTS: Using the derived equation (ESPVR = ESP/(SV/(1.125-1.25(PEP/LVET)) - SV), the ESPVR for the normal group of 6 averaged 2.72 +/- 0.71 and was significantly different from the 1.04 +/- 0.45 found in 6 patients with known systolic dysfunction. In a further test of the method, 15 patients who received concurrent echocardiographic and IC evaluations were found to have calculated ESPVR values that significantly correlated with determined ejection fractions (r = 0.83, p < 0.01). CONCLUSIONS: A noninvasive method for estimating the ESPVR that differentiates the myocardial contractile state in the clinically setting was derived using parameters obtained from IC. While further studies are needed to correlate this new equation with invasive measurements, this method has the potential for easily estimating load independent contractility in patients with cardiac dysfunction.

Adult↗

[The clinical course and cardiohemodynamic status of patients with different variants of diphtheritic myocarditis].

The clinical course was studied as was the condition of cardiohemodynamics in 126 patients with different variants of diphtherial myocarditis (DM) versus 23 patients with unspecific infectious and allergic myocarditis (UIAM). Early DM in the majority of cases runs a moderately severe or severe course because of a stronger--by comparison with late DM and UIAM--predisposition to cardiac insufficiency, sinus bradycardia and heart blocks as well as of a moderately severe systolic dysfunction of the left ventricle (LV), as evidenced by Echo-CG. Late DM runs, on the whole, a mild course, and is associated with minimal LV systolic function inadequacies.

Acute Disease↗

Diastolic heart failure.

Diastolic heart failure is a distinct clinical entity increasingly seen in older patients and requires special awareness to make the diagnosis. Although no single laboratory test is identified for making a confident diagnosis of diastolic dysfunction as the pathogenetic mechanism for heart failure, a constellation of echocardiographic and radionuclear findings are helpful in most cases. Invasive assessment of LV diastole is laborious, requiring high-fidelity pressures and accurate measures of volumes, and these are rarely needed to diagnose the condition. It appears that prognosis is significantly better for those with normal systolic function, when compared with congestive heart failure caused by impaired systolic pump function. Finally, the therapeutic approaches are substantially different for the two groups. It must be emphasized that even patients with predominant myocardial systolic dysfunction have some combined diastolic dysfunction as well. This latter group is difficult to treat. However, improvement in systolic pump function, when markedly impaired, must take precedence in management strategies.

Diastole↗

Deficiency of actinin-associated LIM protein alters regional right ventricular function and hypertrophic remodeling.

Targeted deletion of actinin-associated LIM protein (ALP) in mice leads to right ventricular (RV) dysplasia and a mild RV cardiomyopathy. Although the phenotype has been thoroughly characterized, the mechanisms leading from the cytoskeletal defect to the disease are unclear. We hypothesized that ALP deficiency may be associated with (1) changes in regional systolic dysfunction and (2) regional dysregulation of hypertrophic growth, in accordance with the restricted expression of ALP in the outflow tract of the RV. We examined RV regional epicardial systolic strains with respect to end-diastole in ALP knockout (ALPKO) mice and wild-type controls using an open-chest preparation. Strain components were consistently lower in the ALPKO mice than wild-type controls (second principal strain E2: p = 0.05). RV pressure was slightly but not significantly lower in ALPKO mice as well. To assess regional growth, geometric remodeling was analyzed in ALPKO and wild-type mice after 4 weeks of chronic hypoxia (11% oxygen). The average amount of RV wall thickening in response to hypoxia was reduced to 11% in the ALPKO mice compared with 44% in the wild-type controls. In summary, the results are consistent with the view that disruption of ALP is associated with diminished RV contractile function as well as altered hypertrophic remodeling.

Animals↗

Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction.

AIMS: To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). METHODS: The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and/or LVSD. AF was assessed at presentation and at randomization (median 4.9 days after symptom onset). Primary outcomes were risk of death and major CV events 3 years following acute MI. RESULTS: A total of 1812 with current AF (AF between presentation and randomization), 339 patients with prior AF (history of AF without current AF), and 12,509 without AF were enrolled. Patients with AF were older; had more prior HF, angina, and MI, and received beta-blockers and thrombolytics less often than those without AF. Three-year mortality estimates were 20% in those without AF, 37% with current AF, and 38% with prior AF. Compared with patients without AF, the multivariable adjusted HR of death was 1.25 (1.03-1.52; p=0.03) for prior AF and 1.32 (1.20-1.45; p<0.0001) for current AF. HR for major CV events was 1.15 (0.98-1.35; p=0.08) and 1.21 (1.12-1.31; p<0.0001). CONCLUSION: AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD.

Acute Disease↗

Prediction of the changes in cardiac output in association with preload reduction therapy in patients with hypertensive heart failure.

In treating patients with acute hypertensive heart failure we often try preload-reduction therapy using diuretics or vasodilators, but this may frequently produce a considerable decrease in cardiac output, particularly in hypertensive patients with diastolic dysfunction. Therefore, it is important from the clinical standpoint to predict the change in cardiac output following preload-reduction therapy. The objective of this study was to assess whether the change in cardiac output in association with preload-reduction therapy is predictable before treatment by analysis of mitral flow velocity patterns in patients with hypertensive heart failure. Changes in left ventricular volumes and cardiac output in association with preload-reduction therapy and Doppler echocardiographic parameters of the mitral flow velocity pattern before treatment were studied in 18 patients with hypertensive heart failure. Cardiac output increased in six patients with systolic dysfunction (fractional shortening < 25%). In the other 12 patients (those with normal systolic function), the changes in cardiac output were homogenous among the patients. In this subset there was a greater decrease in cardiac output in patients with a shorter deceleration time. Thus, analysis of deceleration time of the early diastolic filling wave before treatment may be useful in estimating the change in cardiac output following preload reduction in patients with hypertensive heart failure due to diastolic dysfunction.

Adult↗

Where are all the women with heart failure?

In recent clinical trials of medical therapy for heart failure, only approximately 20% of patients enrolled were women. The reasons for the low enrollment of women have not been clear. Although the incidence of heart failure is higher in men than in women, the prevalence is equal. When men and women with heart failure and a low left ventricular ejection fraction are compared, the women are more symptomatic and have a similarly poor outcome. Because mortality is worse in men than in women in large populations of patients with heart failure, there may be important pathophysiologic differences. Substantial data suggest that women may have diastolic dysfunction more often than men. This difference would explain differences in mortality and the difficulty in enrolling women in studies of medical therapy for heart failure with underlying systolic dysfunction.

Diastole↗

Early detection of cardiac dysfunction: use of the myocardial performance index in patients with anorexia nervosa.

OVERVIEW: Patients with anorexia nervosa have functional cardiac abnormalities secondary to their nutritionally depleted state. These abnormalities include decreased left ventricular (LV) mass and varying degrees of LV systolic dysfunction. Assessment of LV diastolic function and quantitative assessment of right ventricular function are not routinely performed. The myocardial performance index (MPI) is a relatively new, simple, quantitative measure of global myocardial function. The purpose of this study was to evaluate left and right ventricular function in 13 patients with anorexia nervosa with the MPI and compare it to more commonly used echocardiographic measures of ventricular function.

Adolescent↗

Functional importance of the long axis dynamics of the human left ventricle.

The role of longitudinally and circumferentially oriented fibres in left ventricular wall motion was examined by digitising echocardiograms of the mitral ring (whose motion reflects long axis change) and of the standard minor axis in 36 healthy individuals, 36 patients with coronary artery disease, 16 with left ventricular hypertrophy, 44 with mitral valve disease (24 of whom had undergone mitral valve replacement). In the controls long axis shortening significantly preceded minor axis shortening (mean (1 SD) difference 25 (40) ms) so that the minor axis increased more during isovolumic contraction (0.25 v 0.09 cm), indicating that the left ventricle became more spherical. Changes in the long and short axes were synchronous at end ejection and in early diastole in the controls. Epicardial excursion preceded endocardial excursion by 50 (20) ms at its peak. These time relations were consistently disturbed in all patient groups, irrespective of the extent of fractional shortening of the minor axis. The onset of long axis shortening was delayed, and this was often associated with premature shortening of the minor axis, the normal spherical shape change during isovolumic contraction was lost, and peak epicardial and endocardial changes became more synchronous. In patients with coronary disease these changes are the expected consequence of ischaemic injury to longitudinally orientated subendocardial fibres. In left ventricular hypertrophy their presence consistently showed systolic dysfunction when orthodox measures were still normal. They were more pronounced after mitral valve replacement when the papillary muscles had been sectioned; long axis shortening was reduced during systole and prolonged into early diastole, while normal shortening of the minor axis was maintained only by abnormal epicardial excursion. Relations between long and short axis motion in healthy individuals are characteristic, and their loss is an early index of systolic ventricular disease. These disturbances precede changes in orthodox measures such as fractional shortening or peak velocity of circumferential fibre shortening.

Cardiomegaly↗

[Antitachycardia pacing in patients with left ventricular dysfunction and hemodynamically unstable arrhythmias].

UNLABELLED: The use of antitachycardia pacing (ATP) has shown itself to be an effective therapeutic option in the treatment of ventricular tachycardia (VT) in carriers of implantable cardioverter defibrillators (ICD). OBJECTIVE: To assess the safety and efficacy of ATP in ICD carriers with ischemic cardiopathy and systolic dysfunction of the left ventricle (LV) presenting VT badly tolerated hemodynamically. METHODS: We studied five patients (four male and one female), survivors of acute myocardial infarction, mean age 56.4 +/- 15.7 years and an ejection fraction < 35%, submitted to ICD implantation by VT inducible in the electrophysiological study (EPS) and refractory to pharmacologic therapy. In three cases the arrhythmia was syncopal and in two the patients felt palpitations and dizziness (systolic blood pressure < 90 mmHg during VT). The ICDs were implanted between March 1996 and October 1997 by transvenous approach in pectoral position. ATP was used as an initial therapeutic alternative (VT zone with a detection frequency of 160-220/min) according to an empirical programme (n = 3) or, whenever feasible, in accordance with the type of VT interruption during EPS (n = 2). During the follow-up of 11 +/- 6 months (2-18), a periodic assessment of the symptomatology and a detailed analysis of episodes of ventricular arrhythmia detected by ICD were made. RESULTS: Two hundred and fourteen episodes of VT were recorded with a post detection duration of > 2.5 sec treated by ICD. The ATP rate of efficacy was 93%. In 3% of the episodes the ATP did not alter VT; in 2% the rate of VT increased (reduction of the VT cycle > 20%) and in 2% therapeutic exhaustion was observed (after the application of ATP and the maximum number of shocks per episode). In 14 episodes with ATP inefficiency, two syncopes occurred (1% of the total number of episodes treated). CONCLUSION: In this study antitachycardia pacing has proven to be a therapeutic option with high rates of efficacy and safety despite its use in survivors of myocardial infarction with moderate to severe compromise of systolic function of the left ventricle and ventricular arrhythmias with hemodynamic instability.

Aged↗

MRI analysis of right ventricular function in normal and spontaneously hypertensive rats.

Right ventricular structure and function were characterized in spontaneously hypertensive rats (SHR) using non-invasive magnetic resonance imaging (MRI) techniques. These studies therefore complement previous reports preoccupied with left ventricular changes associated with this condition. Eight SHR and eight control normotensive Wistar-Kyoto (WKY) rats were each subdivided into equal age-matched groups of 8 and 12 weeks. The right ventricle was imaged through a series of twelve contiguous 1.37-1.75 mm transverse sections at twelve equally spaced time-points that covered both systole and most of diastole thereby completely reconstructing right ventricular anatomy. This gave measurements of right ventricular myocardial mass that were consistent through all twelve time-points in all four experimental groups throughout their cardiac cycles. However, spontaneous hypertension increased this right ventricular myocardial mass, as well as the end-diastolic (EDV) and end-systolic volumes (ESV). Although stroke volume (SV) was conserved, decreases in ejection fraction (EF), a positive shift in the relationship between SV and EDV, and reduced indices of systolic ejection rates in SHR rats compared with the age-matched normal WKY controls indicated significant systolic dysfunction. Additionally, reductions in the rates of diastolic relaxation suggested the onset of diastolic dysfunction. Thus, the non-invasive nature of MRI has made it possible for the first time to demonstrate alterations in structure of the right ventricle and in quantitative indicators of its systolic and diastolic function in the SHR model of hypertension.

Animals↗

Determining myocardial viability in chronic ischemic left ventricular dysfunction: a prospective comparison of rest-redistribution thallium 201 single-photon emission computed tomography, nitroglycerin-dobutamine echocardiography, and intracoronary myocardial contrast echocardiography.

BACKGROUND: Detection of viable myocardium (VM) has important therapeutic implications for chronic ischemic left ventricular (LV) systolic dysfunction. We compared the ability of nitroglycerin-dobutamine echocardiography (NTG-DE), intracoronary myocardial contrast echocardiography (MCE), and rest-redistribution thallium 201 single-photon emission computed tomography (RRT-SPECT) to detect VM in this setting. METHODS: Patients with LV ejection fraction (LVEF) <40% and multivessel coronary disease suitable for revascularization underwent NTG-DE, MCE, RRT-SPECT, and radionuclide ventriculography to determine baseline LVEF. Myocardial contrast echocardiography was performed using intracoronary injection of Albunex. Patients who underwent revascularization had 3-month postprocedural radionuclide ventriculography and transthoracic echocardiography to assess functional recovery. RESULTS: Of 512 myocardial segments in the 32 patients studied, 309 were akinetic or dyskinetic at baseline. Nitroglycerin alone increased regional thickening in 20% of segments with contractile reserve. By RRT-SPECT, 93% of nitroglycerin-responsive segments were viable. Myocardial contrast echocardiography had up to 85% sensitivity and 74% specificity for detection of VM diagnosed by RRT-SPECT. In the 23 patients who underwent revascularization, 54% of akinetic segments showed improved contractility, and mean LVEF increased from 32% to 37% (P = .04). Sensitivities and specificities for detecting functional recovery were 95% and 37% for RRT-SPECT, up to 87% and 48% for MCE, and 63% and 83% for a biphasic response during NTG-DE. CONCLUSIONS: In patients with chronic ischemic LV dysfunction, RRT-SPECT had the highest sensitivity, and NTG-DE, the best specificity for detection of VM. Nitroglycerin facilitated detection of VM and may be a useful adjunct to dobutamine stimulation.

Aged↗

[Interconnection between segmentary contractility and dysfunction of left ventricle in patients with post-infarct cardiosclerosis ].

Intracardiac hemodynamics and segmental contractility were studied in 227 patients with postinfarction cardiosclerosis without ischemic cardiomyopathy and chronic aneurysm. Decreased ejection fraction (EF < 50%) was noted in 41 (18.1%) patients. Systolic dysfunction was frequently observed in patients with the local contractility index (LCI) exceeding 1.25. The highest degree of the left ventricular end-diastolic diameter (EDD) and end-diastolic volume (EDV) was evidenced by the anteroseptal localization of the postinfarction scar. The diastolic dysfunction of the left ventricle was mostly observed in patients with LCI less than 1.25 and posterolateral localization of scar.

Adult↗

Clinical characteristics and echocardiographic features of black men vs. black women with systolic heart failure.

PURPOSE: We sought to determine whether significant differences exist in clinical characteristics and echocardiographic features between black men and black women who presented to an outpatient heart failure clinic. METHODS: A retrospective review of the charts of 114 consecutive patients with systolic dysfunction who presented to a heart failure clinic in Brooklyn from 1999--2003 was performed. The first echocardiogram within six months of presentation to the clinic was used for analysis. The clinical characteristics included are: age, sex, body mass index (BMI) and diabetes status. A significance level of <0.05 was used throughout. SUMMARY: Based on the analysis of 108 black men and women, overall, men have a significantly larger left ventricular end-diastolic diameter (LVEDD) compared to women (p<0.006). Younger men (7.17 cm) had a larger LVEDD compared to older men (6.37 cm) and both younger and older women (6.22 cm and 6.40 cm, respectively). This difference in LVEDD between the sexes decreased with aging. Men (22.17) had a lower ejection fraction (EF) than women (25.37). No significant differences were noted in the BMI (30.45 for men and 28.60 for women) and the albumin level (3.59 for men and 3.44 for women) between the sexes. However, the younger age group (particularly younger men) had a higher BMI than the older age group (p=0.008).

Aged↗

Natriuretic peptide measurement as a screening test for overt and subclinical heart failure.

The prevalence of heart failure will increase in a number of industrialized countries as the proportion of elderly within the population increases. Despite recent advances in medical and surgical intervention, the prognosis for this disorder has not improved significantly. To make a major impact on the prognosis for heart failure, it would be important to be able to recognize various forms of heart disease before severe heart failure has developed. Chest X-radiography, ECG and echocardiography may not be adequate screening tools for heart failure in large populations. Natriuretic peptides are secreted from the heart in response to various cardiac abnormalities including ventricular dysfunction, volume overload, hypertrophy, and myocardial ischemia. Circulating levels of natriuretic peptides are elevated in various forms of structural cardiac disease regardless of etiology and the degree of ventricular systolic dysfunction. Natriuretic peptides, specifically B-type natriuretic peptide, are practically stable and can be measured without an extraction procedure. We have reviewed the recent status of plasma natriuretic peptide measurement for identification of patients with congestive heart failure, left ventricular dysfunction, and high risk of heart failure, especially in mass screening settings.

Atrial Natriuretic Factor↗