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1.  Risk assessment of left ventricular systolic dysfunction in primary care: cross sectional study evaluating a range of diagnostic tests 
BMJ : British Medical Journal  2000;320(7229):220-224.
To assess the probability of left ventricular systolic dysfunction without echocardiography in patients from general practice.
Cross sectional study using multivariate regression models to examine the relation between clinical variables and left ventricular systolic dysfunction as determined by echocardiography.
Three general practices in Copenhagen.
2158 patients aged >40 years were screened by questionnaires and case record reviews; 357 patients with past or present signs or symptoms of heart disease were identified, of whom 126 were eligible for and consented to examination.
Main outcome measures
Clinical variables that were significantly (P<0.05) related to ejection fraction ⩽0.45 and their predictive value for left ventricular systolic dysfunction.
15 patients (12%) had left ventricular systolic dysfunction. The prevalence was significantly related to three questions: does the electrocardiogram have Q waves, left bundle branch block, or ST-T segment changes? (P=0.012); is resting supine heart rate greater than the simultaneous diastolic blood pressure? (P=0.002); and is plasma N-terminal atrial natriuretic peptide>0.8 nmol/l? (P=0.040)? Only one of 60 patients with a normal electrocardiogram had systolic dysfunction (2%, 95% confidence interval 0% to 9%) regardless of response to the other two questions. The risk of dysfunction was appreciable in patients with a yes answer to two or three questions (50%, 27% to 73%).
A normal electrocardiogram implies a low risk of left ventricular systolic dysfunction. Patients can be identified for echocardiography on the basis of an abnormal electrocardiogram combined with increased natriuretic peptide concentration or a heart rate greater than diastolic blood pressure, or both.
Key messagesEarly treatment of left ventricular systolic dysfunction reduces morbidity, but diagnosis relies on echocardiographyThis study examines methods for assessing the risk of left ventricular systolic dysfunction in patients from primary care with past or present signs or symptoms of heart diseaseRisk can be assessed by three factors: QRS or ST-T changes in the electrocardiogram; increased plasma concentration of N-terminal atrial natriuretic peptide; and tachycardia (supine resting heart rate>diastolic blood pressure)Risk of systolic dysfunction was very low in patients with normal electrocardiographic resultsRisk was high in patients who had an abnormal electrocardiogram in combination with at least one other abnormal result
PMCID: PMC27270  PMID: 10642232
2.  Prevalence of left ventricular systolic dysfunction and heart failure in high risk patients: community based epidemiological study 
BMJ : British Medical Journal  2002;325(7373):1156.
To determine the prevalence of left ventricular systolic dysfunction, and of heart failure due to different causes, in patients with risk factors for these conditions.
Epidemiological study, including detailed clinical assessment, electrocardiography, and echocardiography.
16 English general practices, representative for socioeconomic status and practice type.
1062 patients (66% response rate) with previous myocardial infarction, angina, hypertension, or diabetes.
Main outcome measures
Prevalence of systolic dysfunction, both with and without symptoms, and of heart failure, in groups of patients with each of the risk factors.
Definite systolic dysfunction (ejection fraction <40%) was found in 54/244 (22.1%, 95% confidence interval 17.1% to 27.9%) patients with previous myocardial infarction, 26/321 (8.1%, 5.4% to 11.6%) with angina, 7/388 (1.8%, 0.7% to 3.7%) with hypertension, and 12/208 (5.8%, 3.0% to 9.9%) with diabetes. In each group, approximately half of these patients had symptoms of dyspnoea, and therefore had heart failure. Overall rates of heart failure, defined as symptoms of dyspnoea plus objective evidence of cardiac dysfunction (systolic dysfunction, atrial fibrillation, or clinically significant valve disease) were 16.0% (11.6% to 21.2%) in patients with previous myocardial infarction, 8.4% (5.6% to 12.0%) in those with angina, 2.8% (1.4% to 5.0%) in those with hypertension, and 7.7% (4.5% to 12.2%) in those with diabetes.
Many people with ischaemic heart disease or diabetes have systolic dysfunction or heart failure. The data support the need for trials of targeted echocardiographic screening, in view of the major benefits of modern treatment. In contrast, patients with uncomplicated hypertension have similar rates to the general population.
What is already known on this topicThe prognosis and symptoms of patients with left ventricular systolic dysfunction and heart failure can be greatly improved by modern treatmentsMany patients with heart failure do not have an assessment of left ventricular function, resulting in undertreatment of the conditionWhat this study addsPatients with a history of ischaemic heart disease (especially those with previous myocardial infarction) or diabetes commonly have left ventricular systolic dysfunctionThese patients would be candidates for a targeted echocardiographic screening programmeIn contrast, the yield from screening patients with uncomplicated hypertension would be low
PMCID: PMC133457  PMID: 12433768
3.  Biventricular Pacing (Cardiac Resynchronization Therapy) 
Executive Summary
In 2002, (before the establishment of the Ontario Health Technology Advisory Committee), the Medical Advisory Secretariat conducted a health technology policy assessment on biventricular (BiV) pacing, also called cardiac resynchronization therapy (CRT). The goal of treatment with BiV pacing is to improve cardiac output for people in heart failure (HF) with conduction defect on ECG (wide QRS interval) by synchronizing ventricular contraction. The Medical Advisory Secretariat concluded that there was evidence of short (6 months) and longer-term (12 months) effectiveness in terms of cardiac function and quality of life (QoL). More recently, a hospital submitted an application to the Ontario Health Technology Advisory Committee to review CRT, and the Medical Advisory Secretariat subsequently updated its health technology assessment.
Chronic HF results from any structural or functional cardiac disorder that impairs the ability of the heart to act as a pump. It is estimated that 1% to 5% of the general population (all ages) in Europe have chronic HF. (1;2) About one-half of the patients with HF are women, and about 40% of men and 60% of women with this condition are aged older than 75 years.
The incidence (i.e., the number of new cases in a specified period) of chronic HF is age dependent: from 1 to 5 per 1,000 people each year in the total population, to as high as 30 to 40 per 1,000 people each year in those aged 75 years and older. Hence, in an aging society, the prevalence (i.e., the number of people with a given disease or condition at any time) of HF is increasing, despite a reduction in cardiovascular mortality.
A recent study revealed 28,702 patients were hospitalized for first-time HF in Ontario between April 1994 and March 1997. (3) Women comprised 51% of the cohort. Eighty-five percent were aged 65 years or older, and 58% were aged 75 years or older.
Patients with chronic HF experience shortness of breath, a limited capacity for exercise, high rates of hospitalization and rehospitalization, and die prematurely. (2;4) The New York Heart Association (NYHA) has provided a commonly used functional classification for the severity of HF (2;5):
Class I: No limitation of physical activity. No symptoms with ordinary exertion.
Class II: Slight limitations of physical activity. Ordinary activity causes symptoms.
Class III: Marked limitation of physical activity. Less than ordinary activity causes symptoms. Asymptomatic at rest.
Class IV: Inability to carry out any physical activity without discomfort. Symptoms at rest.
The National Heart, Lung, and Blood Institute estimates that 35% of patients with HF are in functional NYHA class I; 35% are in class II; 25%, class III; and 5%, class IV. (5) Surveys (2) suggest that from 5% to 15% of patients with HF have persistent severe symptoms, and that the remainder of patients with HF is evenly divided between those with mild and moderately severe symptoms.
Overall, patients with chronic, stable HF have an annual mortality rate of about 10%. (2) One-third of patients with new-onset HF will die within 6 months of diagnosis. These patients do not survive to enter the pool of those with “chronic” HF. About 60% of patients with incident HF will die within 3 years, and there is limited evidence that the overall prognosis has improved in the last 15 years.
To date, the diagnosis and management of chronic HF has concentrated on patients with the clinical syndrome of HF accompanied by severe left ventricular systolic dysfunction. Major changes in treatment have resulted from a better understanding of the pathophysiology of HF and the results of large clinical trials. Treatment for chronic HF includes lifestyle management, drugs, cardiac surgery, or implantable pacemakers and defibrillators. Despite pharmacologic advances, which include diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, spironolactone, and digoxin, many patients remain symptomatic on maximally tolerated doses.
The Technology
Owing to the limitations of drug therapy, cardiac transplantation and device therapies have been used to try to improve QoL and survival of patients with chronic HF. Ventricular pacing is an emerging treatment option for patients with severe HF that does not respond well to medical therapy. Traditionally, indications for pacing include bradyarrhythmia, sick sinus syndrome, atrioventricular block, and other indications, including combined sick sinus syndrome with atrioventricular block and neurocardiogenic syncope. Recently, BiV pacing as a new, adjuvant therapy for patients with chronic HF and mechanical dyssynchrony has been investigated. Ventricular dysfunction is a sign of HF; and, if associated with severe intraventricular conduction delay, it can cause dyssynchronous ventricular contractions resulting in decreased ventricular filling. The therapeutic intent is to activate both ventricles simultaneously, thereby improving the mechanical efficiency of the ventricles.
About 30% of patients with chronic HF have intraventricular conduction defects. (6) These conduction abnormalities progress over time and lead to discoordinated contraction of an already hemodynamically compromised ventricle. Intraventricular conduction delay has been associated with clinical instability and an increased risk of death in patients with HF. (7) Hence, BiV pacing, which involves pacing left and right ventricles simultaneously, may provide a more coordinated pattern of ventricular contraction and thereby potentially reduce QRS duration, and intraventricular and interventricular asynchrony. People with advanced chronic HF, a wide QRS complex (i.e., the portion of the electrocardiogram comprising the Q, R, and S waves, together representing ventricular depolarization), low left ventricular ejection fraction and contraction dyssynchrony in a viable myocardium and normal sinus rhythm, are the target patients group for BiV pacing. One-half of all deaths in HF patients are sudden, and the mode of death is arrhythmic in most cases. Internal cardioverter defibrillators (ICDs) combined with BiV pacemakers are therefore being increasingly considered for patients with HF who are at high risk of sudden death.
Current Implantation Technique for Cardiac Resynchronization
Conventional dual-chamber pacemakers have only 2 leads: 1 placed in the right atrium and the other in the right ventricle. The technique used for BiV pacemaker implantation also uses right atrial and ventricular pacing leads, in addition to a left ventricle lead advanced through the coronary sinus into a vein that runs along the ventricular free wall. This permits simultaneous pacing of both ventricles to allow resynchronization of the left ventricle septum and free wall.
Mode of Operation
Permanent pacing systems consist of an implantable pulse generator that contains a battery and electronic circuitry, together with 1 (single-chamber pacemaker) or 2 (dual-chamber pacemaker) leads. Leads conduct intrinsic atrial or ventricular signals to the sensing circuitry and deliver the pulse generator charge to the myocardium (muscle of the heart).
Complications of Biventricular Pacemaker Implantation
The complications that may arise when a BiV pacemaker is implanted are similar to those that occur with standard pacemaker implantation, including pneumothorax, perforation of the great vessels or the myocardium, air embolus, infection, bleeding, and arrhythmias. Moreover, left ventricular pacing through the coronary sinus can be associated with rupture of the sinus as another complication.
Conclusion of 2003 Review of Biventricular Pacemakers by the Medical Advisory Secretariat
The randomized controlled trials (RCTs) the Medical Advisory Secretariat retrieved analyzed chronic HF patients that were assessed for up to 6 months. Other studies have been prospective, but nonrandomized, not double-blinded, uncontrolled and/or have had a limited or uncalculated sample size. Short-term studies have focused on acute hemodynamic analyses. The authors of the RCTs reported improved cardiac function and QoL up to 6 months after BiV pacemaker implantation; therefore, there is level 1 evidence that patients in ventricular dyssynchrony who remain symptomatic after medication might benefit from this technology. Based on evidence made available to the Medical Advisory Secretariat by a manufacturer, (8) it appears that these 6-month improvements are maintained at 12-month follow-up.
To date, however, there is insufficient evidence to support the routine use of combined ICD/BiV devices in patients with chronic HF with prolonged QRS intervals.
Summary of Updated Findings Since the 2003 Review
Since the Medical Advisory Secretariat’s review in 2003 of biventricular pacemakers, 2 large RCTs have been published: COMPANION (9) and CARE-HF. (10) The characteristics of each trial are shown in Table 1. The COMPANION trial had a number of major methodological limitations compared with the CARE-HF trial.
Characteristics of the COMPANION and CARE-HF Trials*
BiV indicates biventricular; ICD, implantable cardioverter defibrillator; EF, ejection fraction; QRS, the interval representing the Q, R and S waves on an electrocardiogram; FDA, United States Food and Drug Administration.
Overall, CARE-HF showed that BiV pacing significantly improves mortality, QoL, and NYHA class in patients with severe HF and a wide QRS interval (Tables 2 and 3).
CARE-HF Results: Primary and Secondary Endpoints*
BiV indicates biventricular; NNT, number needed to treat.
Cleland JGF, Daubert J, Erdmann E, Freemantle N, Gras D, Kappenberger L et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure (CARE-HF). New England Journal of Medicine 2005; 352:1539-1549; Copyright 2003 Massachusettes Medical Society. All rights reserved. (10)
CARE H-F Results: NYHA Class and Quality of Life Scores*
Minnesota Living with Heart Failure scores range from 0 to 105; higher scores reflect poorer QoL.
European Quality of Life–5 Dimensions scores range from -0.594 to 1.000; 1.000 indicates fully healthy; 0, dead
Cleland JGF, Daubert J, Erdmann E, Freemantle N, Gras D, Kappenberger L et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure (CARE-HF). New England Journal of Medicine 2005; 352:1539-1549; Copyright 2005 Massachusettes Medical Society. All rights reserved.(10)
GRADE Quality of Evidence
The quality of these 3 trials was examined according to the GRADE Working Group criteria, (12) (Table 4).
Quality refers to criteria such as the adequacy of allocation concealment, blinding, and follow-up.
Consistency refers to the similarity of estimates of effect across studies. If there is an important unexplained inconsistency in the results, confidence in the estimate of effect for that outcome decreases. Differences in the direction of effect, the size of the differences in effect, and the significance of the differences guide the decision about whether important inconsistency exists.
Directness refers to the extent to which the people interventions and outcome measures are similar to those of interest. For example, there may be uncertainty about the directness of the evidence if the people of interest are older, sicker, or have more comorbid conditions than do the people in the studies.
As stated by the GRADE Working Group, (12) the following definitions were used in grading the quality of the evidence:
High: Further research is very unlikely to change our confidence on the estimate of effect.
Moderate: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low: Any estimate of effect is very uncertain.
Quality of Evidence: CARE-HF and COMPANION
Overall, there is evidence that BiV pacemakers are effective for improving mortality, QoL, and functional status in patients with NYHA class III/IV HF, an EF less than 0.35, a QRS interval greater than 120 ms, who are refractory to drug therapy.
As per the GRADE Working Group, recommendations considered the following 4 main factors:
The tradeoffs, taking into account the estimated size of the effect for the main outcome, the confidence limits around those estimates, and the relative value placed on the outcome
The quality of the evidence (Table 4)
Translation of the evidence into practice in a specific setting, taking into consideration important factors that could be expected to modify the size of the expected effects such as proximity to a hospital or availability of necessary expertise
Uncertainty about the baseline risk for the population of interest
The GRADE Working Group also recommends that incremental costs of health care alternatives should be considered explicitly alongside the expected health benefits and harms. Recommendations rely on judgments about the value of the incremental health benefits in relation to the incremental costs. The last column in Table 5 shows the overall trade-off between benefits and harms and incorporates any risk/uncertainty.
For BiV pacing, the overall GRADE and strength of the recommendation is moderate: the quality of the evidence is moderate/high (because of some uncertainty due to methodological limitations in the study design, e.g., no blinding), but there is also some risk/uncertainty in terms of the estimated prevalence and wide cost-effectiveness estimates (Table 5).
For the combination BiV pacing/ICD, the overall GRADE and strength of the recommendation is weak—the quality of the evidence is low (because of uncertainty due to methodological limitations in the study design), but there is also some risk/uncertainty in terms of the estimated prevalence, high cost, and high budget impact (Table 5). There are indirect, low-quality comparisons of the effectiveness of BiV pacemakers compared with the combination BiV/ICD devices.
A stronger recommendation can be made for BiV pacing only compared with the combination BiV/ICD device for patients with an EF less than or equal to 0.35, and a QRS interval over or equal to 120 ms, and NYHA III/IV symptoms, and refractory to optimal medical therapy (Table 5).
There is moderate/high-quality evidence that BiV pacemakers significantly improve mortality, QoL, and functional status.
There is low-quality evidence that combined BiV/ICD devices significantly improve mortality, QoL, and functional status.
To date, there are no direct comparisons of the effectiveness of BiV pacemakers compared with the combined BiV/ICD devices in terms of mortality, QoL, and functional status.
Overall GRADE and Strength of Recommendation
BiV refers to biventricular; ICD, implantable cardioverter defibrillator; NNT, number needed to treat.
PMCID: PMC3382419  PMID: 23074464
4.  Cohort study of plasma natriuretic peptides for identifying left ventricular systolic dysfunction in primary care 
BMJ : British Medical Journal  1998;317(7157):516-519.
Objectives: To determine whether blood natriuretic peptide concentrations are helpful in identifying or excluding left ventricular systolic dysfunction in stable survivors of acute myocardial infarction.
Design: Comparison of blood natriuretic peptide concentrations with echocardiographic assessment of left ventricular systolic function in a general practice population.
Setting: Practices in Western District of Glasgow audit group.
Subjects: 134 long term survivors of myocardial infarction recalled for echocardiography as part of a primary care secondary prevention audit.
Main outcome measures: Area under the receiver operating curve for brain natriuretic peptide and N-terminal atrial natriuretic peptide.
Results: Brain natriuretic peptide was of some diagnostic utility in identifying the minority of subjects with severe left ventricular dysfunction (area under curve=0.73) but was unable to discriminate between patients with moderately severe dysfunction and those with preserved left ventricular function (area under curve for moderate or severe dysfunction=0.54). The corresponding values for N-terminal atrial natriuretic peptide for severe and moderate or severe dysfunction were 0.55 and 0.56 respectively.
Conclusions: Blood natriuretic peptide concentrations are not useful in identifying important left ventricular systolic dysfunction in stable survivors of myocardial infarction.
Key messages Plasma concentrations of brain and N-terminal atrial natriuretic peptide increase in patients with left ventricular systolic dysfunction Both peptides are stable in blood and can be measured relatively quickly and inexpensively. In this general practice cohort of survivors of myocardial infarction brain natriuretic peptide had some value in identifying patients with severe left ventricular systolic dysfunction as determined by echocardiography Measurement of either peptide concentration was unable to discriminate between patients with moderate left ventricular dysfunction and normal function Brain and N-terminal atrial natriuretic peptide are not useful for detecting left ventricular systolic dysfunction in ordinary clinical practice
PMCID: PMC28647  PMID: 9712601
5.  “Diastolic heart failure” or heart failure caused by subtle left ventricular systolic dysfunction? 
Heart  2002;87(1):29-31.
Objectives: To determine whether patients with suspected heart failure but preserved systolic function, as determined by conventional echocardiographic measures (often said to have “diastolic heart failure), might have subtle left ventricular systolic dysfunction detectable by a new measure of left ventricular systolic function—left ventricular systolic atrioventricular plane displacement.
Design: Observational study.
Setting: Direct access echocardiography.
Patients: 147 patients with suspected heart failure referred by general practitioners.
Measurements: Echocardiographic assessment of conventional measures of left ventricular systolic function (fractional shortening, ejection fraction (by Simpson's biplane method) and “eyeball” assessment) and measurement of left ventricular systolic atrioventricular plane displacement.
Results: Between 21% and 33% of patients with “normal” left ventricular systolic function by conventional methods were found to have abnormal left ventricular systolic atrioventricular plane displacement.
Conclusions: Approximately one quarter of patients with suspected heart failure but preserved systolic function by conventional methods have abnormal atrioventricular plane displacement. These patients with suspected heart failure but preserved systolic function by conventional echocardiographic measures may have heart failure caused by subtle systolic dysfunction rather than isolated “diastolic heart failure”.
PMCID: PMC1766950  PMID: 11751660
heart failure; diastole; systole; atrioventricular plane displacement
6.  Prevalence of left ventricular dysfunction in a UK community sample of very old people: the Newcastle 85+ study 
Heart  2012;98(19):1418-1423.
Heart failure (HF) prevalence rises sharply among those aged 85 years and over. Previous population based echocardiographic studies of left ventricular (LV) dysfunction, the substrate for HF, have included only small numbers in this age group. We used domiciliary echocardiography to estimate the prevalence of LV systolic and diastolic dysfunction in 87–89 year olds and the proportion remaining undiagnosed.
Cross sectional analysis of data from Newcastle 85+ Study.
Primary care, North-East England.
376 men and women aged 87–89 years.
Domiciliary echocardiography was performed and LV systolic and diastolic function was graded. The presence of limiting dyspnoea was assessed by questionnaire. Previous diagnoses of HF were abstracted from general practice (GP) records.
32% of participants (119/376) had LV systolic dysfunction (ejection fraction (EF) ≤50%) and a further 20% (75/376) had moderate or severe LV diastolic dysfunction with preserved EF. Both echocardiographic assessment of LV function and dyspnoea status were available in 74% (278/376) of participants. Among these participants, limiting dyspnoea was present in approximately two thirds of those with significant (systolic or isolated moderate/severe diastolic) LV dysfunction. 84% (73/87) of participants with significant LV dysfunction and limiting dyspnoea did not have a pre-existing HF diagnosis in their GP records. Overall, 26% (73/278) of participants with both echocardiographic and dyspnoea data had undiagnosed, symptomatic, significant LV dysfunction.
Significant systolic and diastolic LV dysfunction is much commoner in community dwelling 87–89 year olds than previous studies have suggested. The majority are both symptomatic and undiagnosed.
PMCID: PMC3437786  PMID: 22859497
7.  Left ventricular dysfunction: a clue to cognitive impairment in older patients with heart failure 
OBJECTIVES—Cognitive impairment has been reported in middle aged patients with end stage heart failure. This cross sectional study assessed the prevalence and determinants of cognitive dysfunction in older patients with mild to moderate heart failure.
METHODS—57 consecutive patients (mean age 76.7 years) with chronic heart failure underwent physical examination, blood chemistry, urinalysis, chest radiography ECG, Doppler echocardiography, and the mini mental state examination (MMSE), mental deterioration battery, depression scale of the Center for Epidemiological Studies (CES-D), Katz activities of daily living, and instrumental activities of daily living 24 hours before hospital discharge.
RESULTS—MMSE scores <24 were found in 53% of participants. The MMSE score was associated with left ventricular ejection fraction according to a non-linear correlation, so that cognitive performance was significantly lower in subjects with left ventricular ejection fraction ⩽30%. The same pattern of correlation was evidenced between left ventricular ejection fraction and both the attention sub-item of MMSE and the Raven test score. In a multivariate linear regression model, after adjusting for age, sex, and a series of clinical data and objective tests, both age (β=−0.30; P=0.038) and the natural log of left ventricular ejection fraction (β=0.58; P=0.001) were associated with the MMSE score.
CONCLUSION—Cognitive impairment in older patients with chronic heart failure is common, and independently associated with lower left ventricular ejection fraction. Given the overwhelming incidence and prevalence of heart failure in older populations, early detection of cognitive impairment in these subjects with prompt, intensive treatment of left ventricular systolic dysfunction may prevent or delay a remarkable proportion of dementia in advanced age.

PMCID: PMC2169754  PMID: 9343133
8.  Cross sectional study estimating prevalence of heart failure and left ventricular systolic dysfunction in community patients at risk 
Heart  2001;86(2):172-178.
OBJECTIVE—To examine a general practice population to measure the prevalence of signs and symptoms of heart failure (SSHF) and left ventricular systolic dysfunction (LVSD).
DESIGN—Cross sectional screening study in three general practices followed by echocardiography.
SETTING AND PATIENTS—All patients ⩾ 50 years in two general practices and ⩾ 40 years in one general practice were screened by case record reviews and questionnaires (n = 2158), to identify subjects with some evidence of heart disease. Among these, subjects were sought who had SSHF (n = 115). Of 357 subjects with evidence of heart disease, 252 were eligible for examination, and 126 underwent further cardiological assessment, including 43 with SSHF.
MAIN OUTCOME MEASURES—Prevalence of SSHF as defined by a modified Boston index, LVSD defined as an indirectly measured left ventricular ejection fraction ⩽ 0.45, and numbers of subjects needing an echocardiogram to detect one case with LVSD.
RESULTS—SSHF afflicted 0.5% of quadragenarians and rose to 11.7% of octogenarians. Two thirds were handled in primary care only. At ⩾ 50 years of age 6.4% had SSHF, 2.9% had LVSD, and 1.9% (95% confidence interval 1.3% to 2.5%) had both. To detect one case with LVSD in primary care, 14 patients with evidence of heart disease without SSHF and 5.5 patients with SSHF had to be examined.
CONCLUSION—SSHF is extremely prevalent in the community, especially in primary care, but more than two thirds do not have LVSD. The number of subjects with some evidence of heart disease needing an echocardiogram to detect one case of LVSD is 14.

Keywords: heart failure; left ventricular systolic dysfunction
PMCID: PMC1729862  PMID: 11454835
9.  Positron Emission Tomography for the Assessment of Myocardial Viability 
Executive Summary
The objective was to update the 2001 systematic review conducted by the Institute For Clinical Evaluative Sciences (ICES) on the use of positron emission tomography (PET) in assessing myocardial viability. The update consisted of a review and analysis of the research evidence published since the 2001 ICES review to determine the effectiveness and cost-effectiveness of PET in detecting left ventricular (LV) viability and predicting patient outcomes after revascularization in comparison with other noninvasive techniques.
Left Ventricular Viability
Heart failure is a complex syndrome that impairs the contractile ability of the heart to maintain adequate blood circulation, resulting in poor functional capacity and increased risk of morbidity and mortality. It is the leading cause of hospitalization in elderly Canadians. In more than two-thirds of cases, heart failure is secondary to coronary heart disease. It has been shown that dysfunctional myocardium resulting from coronary heart disease (CAD) may recover contractile function (i.e. considered viable). Dysfunctional but viable myocardium may have been stunned by a brief episode of ischemia, followed by restoration of perfusion, and may regain function spontaneously. It is believed that repetitive stunning results in hibernating myocardium that will only regain contractile function upon revascularization.
For people with CAD and severe LV dysfunction (left ventricular ejection fraction [LVEF] <35%) refractory to medical therapy, coronary artery bypass and heart transplantation are the only treatment options. The opportunity for a heart transplant is limited by scarcityof donor hearts. Coronary artery bypass in these patients is associated with high perioperative complications; however, there is evidence that revascularization in the presence of dysfunctional but viable myocardium is associated with survival benefits and lower rates of cardiac events. The assessment of left ventricular (LV) viability is, therefore, critical in deciding whether a patient with coronary artery disease and severe LV dysfunction should undergo revascularization, receive a heart transplant, or remain on medical therapy.
Assessment of Left Ventricular Viability
Techniques for assessing myocardial viability depend on the measurement of a specific characteristic of viable myocytes such as cell membrane integrity, preserved metabolism, mitochondria integrity, and preserved contractile reserve. In Ontario, single photon emission computed tomography (SPECT) using radioactive 201thallium is the most commonly used technique followed by dobutamine echocardiography. Newer techniques include SPECT using technetium tracers, cardiac magnetic resonance imaging, and PET, the subject of this review.
Positron Emission Tomography
PET is a nuclear imaging technique based on the metabolism of radioactive analogs of normal substrates such as glucose and water. The radiopharmaceutical used most frequently in myocardial viability assessment is F18 fluorodeoxyglucose (FDG), a glucose analog. The procedure involves the intravenous administration of FDG under controlled glycemic conditions, and imaging with a PET scanner. The images are reconstructed using computer software and analyzed visually or semi-quantitatively, often in conjunction with perfusion images. Dysfunctional but stunned myocardium is characterized by normal perfusion and normal FDG uptake; hibernating myocardium exhibits reduced perfusion and normal/enhanced FDG uptake (perfusion/metabolism mismatch), whereas scar tissue is characterized by reduction in both perfusion and FDG uptake (perfusion/metabolism match).
Review Strategy
The Medical Advisory Secretariat used a search strategy similar to that used in the 2001 ICES review to identify English language reports of health technology assessments and primary studies in selected databases, published from January 1, 2001 to April 20, 2005. Patients of interest were those with CAD and severe ventricular dysfunction being considered for revascularization that had undergone viability assessment using either PET and/or other noninvasive techniques. The outcomes of interest were diagnostic and predictive accuracy with respect to recovery of regional or global LV function, long-term survival and cardiac events, and quality of life. Other outcomes of interest were impact on treatment decision, adverse events, and cost-effectiveness ratios.
Of 456 citations, 8 systematic reviews/meta-analyses and 37 reports on primary studies met the selection criteria. The reports were categorized using the Medical Advisory Secretariat levels of evidence system, and the quality of the reports was assessed using the criteria of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) developed by the Centre for Dissemination of Research (National Health Service, United Kingdom). Analysis of sensitivity, specificity, predictive values and likelihood ratios were conducted for all data as well as stratified by mean left ventricular ejection fraction (LVEF). There were no randomized controlled trials. The included studies compared PET with one or more other noninvasive viability tests on the same group of patients or examined the long-term outcomes of PET viability assessments. The quality assessment showed that about 50% or more of the studies had selection bias, interpreted tests without blinding, excluded uninterpretable segments in the analysis, or did not have clearly stated selection criteria. Data from the above studies were integrated with data from the 2001 ICES review for analysis and interpretation.
Summary of Findings
The evidence was derived from populations with moderate to severe ischemic LV dysfunction with an overall quality that ranges from moderate to low.
PET appears to be a safe technique for assessing myocardial viability.
CAD patients with moderate to severe ischemic LV dysfunction and residual viable myocardium had significantly lower 2-year mortality rate (3.2%) and higher event-free survival rates (92% at 3 years) when treated with revascularization than those who were not revascularized but were treated medically (16% mortality at 2-years and 48% 3-year event-free survival).
A large meta-analysis and moderate quality studies of diagnostic accuracy consistently showed that compared to other noninvasive diagnostic tests such as thallium SPECT and echocardiography, FDG PET has:
Higher sensitivity (median 90%, range 71%–100%) and better negative likelihood ratio (median 0.16, range 0–0.38; ideal <0.1) for predicting regional myocardial function recovery after revascularization.
Specificity (median 73%, range 33%–91%) that is similar to other radionuclide imaging but lower than that of dobutamine echocardiography
Less useful positive likelihood ratio (median 3.1, range 1.4 –9.2; ideal>10) for predicting segmental function recovery.
Taking positive and negative likelihood ratios together suggests that FDG PET and dobutamine echocardiography may produce small but sometimes important changes in the probability of recovering regional wall motion after revascularization.
Given its higher sensitivity, PET is less likely to produce false positive results in myocardial viability. PET, therefore, has the potential to identify some patients who might benefit from revascularization, but who would not have been identified as suitable candidates for revascularization using thallium SPECT or dobutamine echocardiography.
PET appears to be superior to other nuclear imaging techniques including SPECT with 201thallium or technetium labelled tracers, although recent studies suggest that FDG SPECT may have comparable diagnostic accuracy as FDG PET for predicting regional and global LV function recovery.
No firm conclusion can be reached about the incremental value of PET over other noninvasive techniques for predicting global function improvement or long-term outcomes in the most important target population (patients with severe ischemic LV dysfunction) due to lack of direct comparison.
An Ontario-based economic analysis showed that in people with CAD and severe LV dysfunction and who were found to have no viable myocardium or indeterminate results by thallium SPECT, the use of PET as a follow-up assessment would likely result in lower cost and better 5-year survival compared to the use of thallium SPECT alone. The projected annual budget impact of adding PET under the above scenario was estimated to range from $1.5 million to $2.3 million.
In patients with severe LV dysfunction, that are deemed to have no viable myocardium or indeterminate results in assessments using other noninvasive tests, PET may have a role in further identifying patients who may benefit from revascularization. No firm conclusion can be drawn on the impact of PET viability assessment on long-term clinical outcomes in the most important target population (i.e. patients with severe LV dysfunction).
PMCID: PMC3385418  PMID: 23074467
10.  Impact of chronic obstructive pulmonary diseases on left ventricular diastolic function in hospitalized elderly patients 
To evaluate the impact of chronic obstructive pulmonary disease (COPD) on left ventricular (LV) diastolic function in hospitalized elderly patients.
This was a case–control observational study of 148 consecutive hospitalized elderly patients (≥65 years old): 73 subjects without COPD as controls and 75 patients with COPD. Mild-to-moderate COPD was defined as stages 1 and 2, while severe and very severe COPD was defined as stages 3 and 4, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. Clinical characteristics and echocardiographic parameters were analyzed and compared.
Compared with the control group, patients with COPD had a higher frequency of LV diastolic dysfunction and heart failure with preserved ejection fraction. Smoking frequency, frequency of cerebrovascular diseases and diabetes, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the COPD group (all P<0.05). COPD patients showed more abnormalities in diastolic function (E/e′: 11.51±2.50 vs 10.42±3.25, P=0.047), but no differences in systolic function and right ventricular function (all P>0.05). Patients with severe/very severe COPD showed no differences in LV diastolic function compared to patients with mild/moderate COPD (P>0.05), but serum NT-proBNP levels were higher in severe/very severe COPD (P<0.05).
Results suggest that early-stage COPD may have an impact on the LV diastolic function. Severe COPD mainly affected right ventricular function. In hospitalized elderly patients with COPD, LV diastolic dysfunction should be taken into account together with right ventricular function.
PMCID: PMC4279668  PMID: 25565790
chronic obstructive pulmonary disease; heart failure; left ventricular diastolic dysfunction; elderly; echocardiography
11.  Association of serum total bilirubin levels with diastolic dysfunction in heart failure with preserved ejection fraction 
Biological Research  2014;47(1):7.
Left ventricular diastolic dysfunction is one of the main characteristics of heart failure patients with a preserved left ventricular ejection fraction. As bilirubin is regarded as an important endogenous antioxidant molecule, serum total bilirubin levels were compared between heart failure patients with a preserved left ventricular ejection fraction and normal controls in this study. We recruited 327 heart failure patients with a preserved left ventricular ejection fraction and 200 healthy controls. Patients were divided into 4 subgroups by their comprehensive echocardiographic manifestations, 1-mild, 2-moderate, 3-severe (reversible restrictive), 4-severe (fixed restrictive). Total bilirubin levels were compared using stepwise multiple regressions adjusted for selected factors.
After adjusting for gender, age, smoking, systolic blood pressure, diastolic blood pressure, total cholesterol and triglyceride, serum total bilirubin levels were significantly lower in the heart failure group compared with the control group (P < 0.01). Patients in the subgroup (4-severe) showed significantly (P < 0.05) lower levels of total bilirubin when compared with the subgroup (1-mild).
TB level was negatively correlated with left ventricular diastolic dysfunction in heart failure patients with a preserved left ventricular ejection fraction, which might provide a new insight into the complicated mechanisms of heart failure with a preserved left ventricular ejection fraction.
PMCID: PMC4101732  PMID: 25027460
Bilirubin; Heart failure; Diastolic dysfunction; Echocardiography
12.  Detection of left ventricular dysfunction after acute myocardial infarction: comparison of clinical, echocardiographic, and neurohormonal methods. 
British Heart Journal  1994;72(1):16-22.
OBJECTIVE--The SAVE study showed that captopril improves mortality in patients with left ventricular dysfunction after myocardial infarction and that this benefit occurred even in patients with no clinically overt heart failure. On the basis of this, it seems important to identify correctly which patients have left ventricular dysfunction after a myocardial infarction. The objective was to compare various methods of identifying patients with left ventricular dysfunction (left ventricular ejection fraction, LVEF, < or = 40%) after acute myocardial infarction. The methods compared were echocardiography (quantitative and qualitative visual assessment), clinical evaluation (subjective assessment and three clinical score methods), and measurement of plasma concentrations of cardiac natriuretic peptide hormones (atrial and brain natriuretic peptides, ANP and BNP). DESIGN--Cross sectional study of left ventricular function in patients two to eight days after acute myocardial infarction. SETTING--Coronary care unit of a teaching hospital. PATIENTS--75 survivors of a recent myocardial infarction aged 40 to 88 with no history of cardiac failure and without cardiogenic shock at the time of entry to the study. MAIN OUTCOME MEASURES--Sensitivities and specificities of the various methods of detecting left ventricular dysfunction were calculated by comparing them with a cross sectional echocardiographic algorithm for LVEF. RESULTS--Clinical impression was poor at identifying LVEF < 40% (sensitivity 46%). Clinical scoring improved this figure somewhat (modified Peel index sensitivity 64%). Qualitative visual assessment echocardiography was a more sensitive method (sensitivity 82%) for detecting LVEF < 40%. Plasma BNP concentration was also a sensitive measure for detecting left ventricular dysfunction (sensitivity 84%) but plasma ANP concentration was much poorer (sensitivity 64%). CONCLUSION--Left ventricular dysfunction is easily and reliably detected by echocardiographic measurement of LVEF and also by a quick qualitative echocardiographic assessment but is likely to be missed by clinical assessment alone. High concentrations of plasma BNP maybe another useful indicator of left ventricular dysfunction, particularly in hospitals where not all patients can be screened by echocardiography or radionuclide ventriculography after myocardial infarction.
PMCID: PMC1025420  PMID: 7741839
13.  Prevalence of Ventricular Arrhythmia and Its Associated Factors in Nondialyzed Chronic Kidney Disease Patients 
PLoS ONE  2013;8(6):e66036.
Background and Objectives
Sudden cardiac death is the most common cause of mortality in chronic kidney disease patients, and it occurs mostly due to ventricular arrhythmias. In this study, we aimed at investigating the prevalence of ventricular arrhythmia and the factors associated with its occurrence in nondialyzed chronic kidney disease patients.
Design, Setting, Participants and Measurements
This cross-sectional study evaluated 111 chronic kidney disease patients (estimated glomerular filtration rate 34.7±16.1 mL/min/1.73 m2, 57±11.4 years, 60% male, 24% diabetics). Ventricular arrhythmia was assessed by 24-hour electrocardiogram. Left ventricular hypertrophy (echocardiogram), 24-hour ambulatory blood pressure monitoring, and coronary artery calcification (multi-slice computed tomography) and laboratory parameters were also evaluated.
Ventricular arrhythmia was found in 35% of the patients. Non-controlled hypertension was observed in 21%, absence of systolic decency in 29%, left ventricular hypertrophy in 27%, systolic dysfunction in 10%, and coronary artery calcification in 49%. Patients with ventricular arrhythmia were older (p<0.001), predominantly men (p = 0.009), had higher estimated glomerular filtration rate (p = 0.03) and hemoglobin (p = 0.005), and lower intact parathyroid hormone (p = 0.024) and triglycerides (p = 0.011) when compared to patients without ventricular arrhythmia. In addition, a higher left ventricular mass index (p = 0.002) and coronary calcium score (p = 0.002), and a lower ejection fraction (p = 0.001) were observed among patients with ventricular arrhythmia. In the multiple logistic regression analysis, aging, increased hemoglobin levels and reduced ejection fraction were independently related to the presence of ventricular arrhythmia.
Ventricular arrhythmia is prevalent in nondialyzed chronic kidney disease patients. Age, hemoglobin levels and ejection fraction were the factors associated with ventricular arrhythmia in these patients.
PMCID: PMC3676379  PMID: 23762460
14.  Prevalence of impaired left ventricular systolic function and heart failure in a middle aged and elderly urban population segment of Copenhagen 
Heart  2003;89(12):1422-1429.
Objective: To assess the prevalence of impaired left ventricular systolic function and manifest heart failure in a general population aged 50–89 years.
Design: In this cross sectional survey, participants filled in a heart failure questionnaire. ECG, blood tests, and echocardiography were performed.
Setting: The study population was recruited from general practitioners situated in the same urban area and examined in a university hospital in Copenhagen, Denmark.
Participants: 764 participants (432 women and 332 men, median (SD) age 66 (11) years) participated. The study population was stratified to include a minimum of 150 persons in each age decade.
Main outcome measures: Prevalence of impaired systolic function and manifest heart failure.
Results: The prevalence of systolic dysfunction (left ventricular ejection fraction ⩽ 40%) was more than twice as high among men (7.6%) as among women (2.6%). In the male population systolic heart failure (left ventricular ejection fraction ⩽ 40% and symptoms) was found in 1.8% of the 50–59 years age group and approximately doubled for each age decade to reach 13.9% in octogenarians. Among women systolic dysfunction increased from 0.8% to 4.3% in the same age groups. Asymptomatic cases accounted for 44.0% of all cases of systolic dysfunction in the male population and only 9.1% in the female population.
Conclusions: In this age controlled population study impaired left ventricular systolic function and heart failure increased substantially with age and was more than twice as frequent among men as among women. Asymptomatic left ventricular dysfunction occurred more frequently in men than in women and was less prevalent with increasing age.
PMCID: PMC1767972  PMID: 14617553
epidemiology; prevalence; systolic function; heart failure
15.  Recovery pattern of left ventricular dysfunction following radiofrequency ablation of incessant supraventricular tachycardia in infants and children 
Heart  1998;79(6):588-592.
Objective—To assess recovery pattern of left ventricular function secondary to incessant tachycardia after radiofrequency ablation in a group of infants and children.
Design and setting—A combined prospective and retrospective echocardiographic study carried out in a tertiary paediatric cardiac centre.
Patients—Echocardiographic evaluation of left ventricular size and function in nine children with incessant tachycardia, before and after successful radiofrequency ablation. Age at ablation ranged from 2 months to 12.5 years (mean 4.1 years). Recovery of left ventricular function was analysed in relation to age at ablation (group I < 18 months, group II > 18 months).
Main outcome measure—Ventricular recovery pattern.
Results—Seven of the nine children had left ventricular dysfunction; six of these also had left ventricular dilatation. All children with left ventricular dysfunction had normalisation of ejection fraction and fractional shortening; left ventricular dilatation also improved, but the improvement occurred after recovery of function. There was a shorter recovery time for left ventricular function in younger (group I) than in older children (group II) (mean (SD) 5.7 (7.2) months v 31.3 (5.2) (p < 0.002).
Conclusions—Tachycardia induced cardiomyopathy is reversible following curative treatment with radiofrequency. Recovery of left ventricular systolic function precedes recovery of left ventricular dilatation. Time course to recovery is shorter in younger children.

 Keywords: radiofrequency ablation;  left ventricular dysfunction;  incessant tachycardia;  echocardiography;  children
PMCID: PMC1728732  PMID: 10078086
16.  Left ventricular morphology and diastolic function in uraemia: echocardiographic evidence of a specific cardiomyopathy. 
British Heart Journal  1995;74(2):174-179.
OBJECTIVE--To see whether cardiac morphological and functional abnormalities in uraemic patients are determined by high blood pressure or if they are an expression of a specific cardiomyopathy. DESIGN--Cross sectional study. SETTING--City general hospital in Italy. SUBJECTS--35 uraemic patients receiving haemodialysis (17 men, 18 women; mean age 60.3 (11.2); mean duration of dialysis 52 months) were selected from the 64 patients in Venice who were receiving dialysis; subjects with diabetes, haemochromatosis, valvar dysfunction, regional dyskinesias, and pericarditis were excluded. 19 control normotensive subjects (6 men and 13 women), matched for age. MAIN OUTCOME MEASURES--Echocardiographic measurements of left atrium, left ventricular end diastolic and end systolic volume, aortic root diameter, posterior wall and interventricular septum thickness, left ventricle mass index, and ejection fraction in controls and in patients according to whether they were normotensive (five men, eight women) or hypertensive (12 men, 10 women) on 48 hour ambulatory monitoring; left ventricular diastolic function by Doppler ultrasonography. RESULTS--Mean systolic and diastolic pressures, daytime systolic and diastolic pressures, and night time systolic and diastolic pressures were significantly higher in the hypertensive patients than in the normotensive patients. The normotensive patients had similar blood pressures to the controls. Left ventricular mass correlated significantly with the mean diastolic pressure and mean night time systolic and diastolic pressures. Parathyroid hormone concentrations were similar in the two groups of patients. Diastolic relaxation was impaired to the same degree in the two groups of patients. Parameters of diastolic function showed no relation to left ventricular mass, which was significantly higher in the hypertensive than in the normotensive patients. CONCLUSIONS--Uraemia is likely to induce specific changes in the relaxation properties of the myocardium. These changes are responsible for the impaired diastolic function independently of blood pressure, degree of hypertrophy, and metabolic changes, which suggests the existence of a specific cardiomyopathy. Hypertension remains a determinant of left ventricular mass.
PMCID: PMC483995  PMID: 7546998
17.  Prevalence and Prognosis of Asymptomatic Left Ventricular Diastolic Dysfunction in Ambulatory Patients With Coronary Heart Disease 
The American journal of cardiology  2007;99(12):1643-1647.
The association of asymptomatic left ventricular (LV) diastolic dysfunction with cardiovascular outcomes in ambulatory patients with coronary heart disease (CHD) and no history of heart failure (HF) was examined. LV diastolic HF predicts adverse cardiovascular outcomes. However, the prevalence and prognosis of asymptomatic LV diastolic dysfunction in patients with established CHD in the absence of clinical HF is unknown. Six hundred ninety-three patients with stable CHD, normal systolic function (LV ejection fraction ≥50%), and no history of HF were evaluated. Echocardiography was used to classify LV diastolic function, and Cox proportional hazards models were used to evaluate the association of LV diastolic dysfunction with cardiovascular outcomes during 3 years of follow-up. Of 693 subjects with normal systolic function and no history of HF, 455 (66%) had normal LV diastolic function, 166 (24%) had mild LV diastolic dysfunction, and 72 (10%) had moderate to severe LV diastolic dysfunction. After multivariable adjustment, the presence of moderate to severe LV diastolic dysfunction was strongly predictive of incident hospitalization for HF (hazard ratio 6.3, 95% confidence interval 2.4 to 16.1, p = 0.0003) and death from heart disease (HR 3.9, 95% confidence interval 1.0 to 14.8, p = 0.05). In conclusion, moderate to severe LV diastolic dysfunction was present in 10% of patients with stable CHD with normal ejection fraction and no history of HF and predicts subsequent hospitalization for HF and death from heart disease. Patients with asymptomatic LV diastolic dysfunction may benefit from more aggressive therapy to prevent or delay the development of HF.
PMCID: PMC2778467  PMID: 17560867
18.  Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey 
BMJ : British Medical Journal  1998;317(7158):565-570.
Objectives: To assess the relation between white coat hypertension and alterations of left ventricular structure and function.
Design: Cross sectional survey.
Setting: Augsburg, Germany.
Subjects: 1677 subjects, aged 25 to 74 years, who participated in an echocardiographic substudy of the monitoring of trends and determinants in cardiovascular disease Augsburg study during 1994-5.
Outcome measures: Blood pressure measurements and M mode, two dimensional, and Doppler echocardiography. After at least 30 minutes’ rest blood pressure was measured three times by a technician, and once by a physician after echocardiography. Subjects were classified as normotensive (technician <140/90 mm Hg, physician <160/95 mm Hg; n=849), white coat hypertensive (technician <140/90 mm Hg, physician ⩾160/95 mm Hg; n=160), mildly hypertensive (technician ⩾140/90 mm Hg, physician <160/95 mm Hg; n=129), and sustained hypertensive (taking antihypertensive drugs or blood pressure measured by a technican ⩾140/90 mm Hg, and physician ⩾160/95 mm Hg; n=538).
Results: White coat hypertension was more common in men than women (10.9% versus 8.2% respectively) and positively related to age and body mass index. After adjustment for these variables, white coat hypertension was associated with an increase in left ventricular mass and an increased prevalence of left ventricular hypertrophy (odds ratio 1.9, 95% confidence interval 1.2 to 3.2; P=0.009) compared with normotensive patients. The increase in left ventricular mass was secondary to significantly increased septal and posterior wall thicknesses whereas end diastolic diameters were similar in both groups with white coat hypertension or normotension. Additionally, the systolic white coat effect (difference between blood pressures recorded by a technician and physician) was associated with increased left ventricular mass and increased prevalence of left ventricular hypertrophy (P<0.05 each). Values for systolic left ventricular function (M mode fractional shortening) were above normal in subjects with white coat hypertension whereas diastolic filling and left atrial size were similar to those in normotension.
Conclusion: About 10% of the general population show exaggerated inotropic and blood pressure responses when mildly stressed. This is associated with an increased risk of left ventricular hypertrophy.
Key messages About 10% of the general population display white coat hypertension After adjustment for age, body mass index, and baseline blood pressure, white coat hypertension is associated with increased left ventricular mass and increased risk of left ventricular hypertrophy In white coat hypertension, after adjustment for covariates, systolic function has values above normal whereas diastolic filling is unchanged White coat hypertension cannot be dismissed as a benign condition
PMCID: PMC28649  PMID: 9721112
19.  Evaluation of Cardiac Function in Patients with Thalassemia Intermedia 
Thalassemia intermedia is a variety of beta thalassemia which shows clinical symptoms somewhere between asymptomatic carriers and thalassemia major. Cardiac dysfunctions due to chronic anemia and hemosiderosis are the major causes of death in these patients. The purpose of this study is to evaluate cardiac function in these patients by echocardiography.
Materials and Methods
This case-control study was conducted on 22 thalassemic patients (mean: 16.5±5.8 years) and 66 healthy individuals (mean:16.07± 2.9years) as a control group from January 2007 to July 2008. There was no sign of cardiac involvement by physical examination, chest x-ray and ECG in patients. Echocardiographic parameters were measured in groups, and finally data was analyzed by SPSS software.
The mean of left ventricular myocardial performance index (MPI) (P-value=0.0001) and left ventricular mass index (LVMI) (P-value=0.0001) have statistically significant difference. Mean of interventricular septal dimension in diastole (IVSD), left ventricular posterior wall thickness in diastole (LVPWD), interventricular septal dimension in systole (IVSS) and left ventricular posterior wall dimension in systole (LVPWS) were also statistically significant with a P-value of, 0.002, 0.001, 0.01, 0.003, respectively. Aortic Pre-ejection period/Ejection time (PEP/ET) (P-value=0.009), ejection fraction (EF) (P-value=0.019), fractional shortening (SF) (P-value=0.041), left ventricular isovolumetric contraction time (ICT) (P-value=0.0001) and left ventricular isovolumetric relaxation time (IRT) (P-value=0.0001) were statistically significant. Mean of right ventricular MPI (P-value=0.0001) and IRT (P-value=0.0001) were also significantly different between two groups. Others echocardiographic parameters were not statistically significant (P-value>0.05).
Heart failures are earlier affected thalassemia intermedia patients compared with control group.
PMCID: PMC3915442  PMID: 24575263
Heart failure; Anemia; beta-Thalassemia
20.  Plasma proatrial natriuretic factor (1-98) concentration after myocardial infarction: relation to indices of cardiac and renal function. 
British Heart Journal  1995;73(6):511-516.
OBJECTIVES--(a) To assess the relation between plasma concentrations of proatrial natriuretic factor (1-98) and non-invasively derived indices of left ventricular systolic and diastolic performance and (b) to assess the potential confounding effect of renal function and age on this relation in patients with acute myocardial infarction. DESIGN--Cross sectional comparison of biochemical and echocardiographic indices of cardiac function. SETTING--Norwegian central hospital. PATIENTS--Sixty four patients with acute myocardial infarction. MAIN OUTCOME MEASURES--Relation between plasma proatrial natriuretic factor (1-98) concentrations and echocardiographic indices of left ventricular systolic function as assessed by univariate and multivariate linear regression analysis. Sensitivity and specificity of plasma proatrial natriuretic factor (1-98) concentration as a measure of left ventricular systolic and diastolic dysfunction. RESULTS--Plasma proatrial natriuretic factor (1-98) concentrations were significantly related to left ventricular ejection fraction (r = -0.33; P = 0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P < 0.001). In a multivariate model left ventricular ejection fraction and creatinine clearance were both independently related to plasma values. The mean concentration of proatrial natriuretic factor (1-98) was significantly higher in patients with an ejection fraction of < 40% than in those with an ejection fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is ratio of peak early filling velocity to peak atrial component) compared with those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P = 0.02). When patients were subdivided according to the median concentration of proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were 89% and 56% respectively for detecting a left ventricular ejection fraction of < 40% and 75% and 61% respectively for detecting an abnormal E/A ratio. Concentrations below the median had a negative predictive value of 97% in excluding an ejection fraction of < 40% and of 84% in excluding an abnormal E/A ratio. CONCLUSION--These results suggest that soon after myocardial infarction left ventricular ejection fraction and indices of renal function are independently related to plasma concentrations of proatrial natriuretic factor (1-98). Plasma concentrations of proatrial natriuretic factor (1-98) seem to reflect renal and cardiac performance rather than specific haemodynamic variables assessed by noninvasive methods. Plasma proatrial natriuretic factor (1-98) measurements may be a useful screening tool to identify patients with normal cardiac function soon after myocardial infarction.
PMCID: PMC483911  PMID: 7626348
21.  Comparing impedance cardiography and echocardiography in the assessment of reduced left ventricular systolic function 
BMC Research Notes  2013;6:114.
An early and accurate diagnosis of chronic heart failure is a big challenge for a general practitioner. Assessment of left ventricular function is essential for the diagnosis of heart failure and the prognosis. A gold standard for identifying left ventricular function is echocardiography. Echocardiography requires input from specialized care and has a limited access in Swedish primary health care. Impedance cardiography (ICG) is a noninvasive and low-cost method of examination. The survey technique is simple and ICG measurement can be performed by a general practitioner. ICG has been suggested for assessment of left ventricular function in patients with heart failure. We aimed to study the association between hemodynamic parameters measured by ICG and the value of ejection fraction as a determinant of reduced left ventricular systolic function in echocardiography.
A non-interventional, observational study conducted in the outpatients heart failure unit. Thirty-six patients with the diagnosis of chronic heart failure were simultaneously examined by echocardiography and ICG. Distribution of categorical variables was presented as numbers. Distribution of continuous variables was presented as a mean and 95% Confidence Interval. Kruskal-Wallis test was used to compare variables and show differences between the groups. A p-value of <0.05 was considered significant.
We found that three ICG parameters: pre-ejection fraction, left ventricular ejection time and systolic time ratio were significantly associated with ejection fraction measured by echocardiography.
The association which we found between EF and ICG parameters was not reported in previous studies. We found no association between EF and ICG parameters which were suggested previously as the determinants of reduced left ventricular systolic function.
The knowledge concerning explanation of hemodynamic parameters measured by ICG that is available nowadays is not sufficient to adopt the method in practice and use it to describe left ventricular systolic dysfunction.
PMCID: PMC3618318  PMID: 23531417
Heart failure; Reduced left ventricular systolic function; Impedance cardiography; Echocardiography
22.  Biochemical diagnosis of ventricular dysfunction in elderly patients in general practice: observational study 
BMJ : British Medical Journal  2000;320(7239):906-908.
To investigate the usefulness of measuring plasma concentrations of B type natriuretic peptide in the diagnosis of left ventricular systolic dysfunction in an unselected group of elderly people.
Observational study.
General practice with four centres in Poole, Dorset.
155 elderly patients aged 70 to 84 years.
Main outcome measures
Diagnostic characteristics of plasma B type natriuretic peptide measured by radioimmunoassay as a test for left ventricular systolic dysfunction assessed by echocardiography.
The median plasma concentration of B type natriuretic peptide was 39.3 pmol/l in patients with left ventricular systolic dysfunction and 15.8 pmol/l in those with normal function. The proportional area under the receiver operator curve was 0.85. At a cut-off point of 18.7 pmol/l the test sensitivity was 92% and the predictive value 18%.
Plasma concentration of B type natriuretic peptide could be used effectively as an initial test in a community screening programme and, possibly, using a low cut-off point, as a means of ruling out left ventricular systolic dysfunction. It is, however, not a good test to “rule in” the diagnosis, and access to echocardiography remains essential for general practitioners to diagnose heart failure early.
PMCID: PMC27331  PMID: 10741999
23.  Granulocyte colony-stimulating factor therapy for stem cell mobilization following anterior wall myocardial infarction: the CAPITAL STEM MI randomized trial 
Small studies have yielded divergent results for administration of granulocyte colony-stimulating factor (G-CSF) after acute myocardial infarction. Adequately powered studies involving patients with at least moderate left ventricular dysfunction are lacking.
Patients with left ventricular ejection fraction less than 45% after anterior-wall myocardial infarction were treated with G-CSF (10 μg/kg daily for 4 days) or placebo. After initial randomization of 86 patients, 41 in the placebo group and 39 in the G-CSF group completed 6-month follow-up and underwent measurement of left ventricular ejection fraction by radionuclide angiography.
Baseline and 6-week mean ejection fraction was similar for the G-CSF and placebo groups: 34.8% (95% confidence interval [CI] 32.6%–37.0%) v. 36.4% (95% CI 33.5%–39.2%) at baseline and 39.8% (95% CI 36.2%–43.4%) v. 43.1% (95% CI 39.2%–47.0%) at 6 weeks. However, G-CSF therapy was associated with a lower ejection fraction at 6 months relative to placebo (40.8% [95% CI 37.4%–44.2%] v. 46.0% [95% CI 42.7%–44.3%]). Both groups had improved left ventricular function, but change in left ventricular ejection fraction was lower in patients treated with G-CSF than in those who received placebo (5.7 [95% CI 3.4–8.1] percentage points v. 9.2 [95% CI 6.3–12.1] percentage points). One or more of a composite of several major adverse cardiac events occurred in 8 patients (19%) within each group, with similar rates of target-vessel revascularization.
In patients with moderate left ventricular dysfunction following anterior-wall infarction, G-CSF therapy was associated with a lower 6-month left ventricular ejection fraction but no increased risk of major adverse cardiac events. Future studies of G-CSF in patients with left ventricular dysfunction should be monitored closely for safety. Trial registration:, no. NCT00394498
PMCID: PMC4119168  PMID: 24934893
24.  Left Ventricular Function and Exercise Capacity 
Limited information exists regarding the role of left ventricular function in predicting exercise capacity and impact on age- and sex-related differences.
To determine the impact of measures of cardiac function assessed by echocardiography on exercise capacity and to determine if these associations are modified by sex or advancing age.
Cross-sectional study of patients undergoing exercise echocardiography with routine measurements of left ventricular systolic and diastolic function by 2D and Doppler techniques. Analyses were conducted to determine the strongest correlates of exercise capacity and the age- and sex-interactions of these variables with exercise capacity.
Large tertiary referral center in Rochester, MN in 2006.
Patients undergoing exercise echocardiography using the Bruce protocol (n=2,867). Patients with echocardiographic evidence of exercise-induced ischemia, ejection fraction <50% or significant valvular heart disease were excluded.
Main Outcome Measures
Exercise capacity (metabolic equivalents, METs).
Diastolic dysfunction was strongly and inversely associated with exercise capacity. Compared with normal function those with moderate/severe [-1.3 (-1.52 to – 0.99) METs, p<0.0001], and mild resting diastolic dysfunction [-0.70 (-0.88 to -0.46) METs, p<0.0001] had substantially lower exercise capacity after multivariable adjustment. Variation of left ventricular systolic function within the normal range was not associated with exercise capacity. Left ventricular filling pressures measured by resting E/e’ > 15 [-0.42 (-0.70 to -0.11)METs, p=0.004] or post-exercise E/e'> 15 [-0.41 (-0.71 to -0.11), p<0.0001] were similarly associated with a reduction in exercise capacity, each in separate multivariate analyses. Individuals with impaired relaxation or resting E/e’ ≥15 had a progressive increase in the magnitude of reduction in exercise capacity with advancing age (p<0.001 and p=0.02, respectively). Other independent correlates of exercise capacity were age [unstandardized β coefficient -0.85 (95% CI -0.92 to -0.77) METs per 10 year increment, p<0.0001], female sex [-1.98 ( -2.15 to -1.84) METs, p<0.0001], and body mass index >30 kg/m2 [-1.24 (-1.41 to -1.10) METs, p<0.0001],
In this large cross-sectional study of those referred for exercise echocardiography and not limited by ischemia, abnormalities of left ventricular diastolic function were independently associated with exercise capacity.
PMCID: PMC2862454  PMID: 19155455
25.  Long term follow up of patients with endomyocardial fibrosis: effects of surgery 
Heart  1998;79(4):362-367.
Aims—To determine the long term outcome of patients with endomyocardial fibrosis and to compare echocardiographic and haemodynamic data before and after ventricular endocardial resection.
Patients—Seventeen patients (11 women and six men; mean age 35.5 years) diagnosed with endomyocardial fibrosis at the University Hospital in Zurich, Switzerland from 1971 to 1995. Twelve patients (70%) had partial obliteration of both ventricles and in five patients (30%) the fibrotic lesions were limited to the left ventricle. 
Methods—Fourteen of the 17 patients had surgical resection: fibrosis was resected from both ventricles in five patients and from the left ventricle only in nine patients. Ten patients had mitral valve replacement and two had tricuspid valve replacement. Left ventricle endocardial resection was done without reconstruction or replacement of the atrioventricular valve in three patients. Preoperative and postoperatve echocardiographic data were available for 11 patients and haemodynamic data for six patients. Patients were followed up for 0.4-19 years (mean 8.6).
Results—Preoperatively four patients were NYHA functional class IV and 10 were class III; postoperatively one patient was class III, seven class II, and six class I. Preoperatively, echocardiography showed obliteration of the left ventricular apex and inflow tract in all patients, which decreased or disappeared after surgery. Left ventricular end diastolic pressure decreased from 25 mm Hg before surgery to 14 mm Hg after successful resection of the fibrosis. Left ventricular end diastolic volume (normal 93 (17) ml/m2) increased from 65 ml/m2 to 97 ml/m2 (p < 0.05) after surgery. Ejection fraction was normal preoperatively (57%) and decreased slightly (52%) after surgery. One patient died five months after surgery from heart failure. Four surgically treated patients died during the follow up period: one each from systolic dysfunction, recurrence of endomyocardial fibrosis, pneumonia, and food poisoning. Overall survival was 65% at five years and 59% at 10 years; the survival rates of the operated patients was 72% and 68%, respectively. Only one of the medically treated patients survived longer than three years from diagnosis.
Conclusions— Endomyocardial fibrosis is a rare disease in European countries and is found mainly in women. The clinical picture is characterised by severe congestive heart failure but heart size is only moderately increased. Systolic performance is normal or only slightly depressed despite severe restriction to filling, atrioventricular valve regurgitation or both. Partial obliteration of the right and/or left ventricle may be detected by echocardiography. Endocardial resection with atrioventricular valve replacement is the treatment of choice with appreciable postoperative improvement and 10 year survival of approximately 70%.

 Keywords: endomyocardial fibrosis;  atrioventricular valve regurgitation;  endocardial resection;  hypereosinophilic syndrome
PMCID: PMC1728653  PMID: 9616343

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