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Frequency of development of acute global left ventricular dysfunction in human immunodeficiency virus infection.

OBJECTIVES: This study evaluated prospectively the frequency, clinical outcome and pathologic findings of acute global left ventricular dysfunction in human immunodeficiency virus (HIV) infection during the various stages of the disease. BACKGROUND: Acute global left ventricular dysfunction in the course of HIV infection is still a poorly defined clinical entity, and little is known about the outcome after the acute onset. METHODS: Between January 1988 and June 1992, 136 HIV-positive (HIV+) patients without clinical, electrocardiographic or echocardiographic evidence of cardiovascular dysfunction on admission were prospectively studied with serial echocardiograms. Patients were assigned to three groups: 1) anti-HIV+ asymptomatic (17 patients, 12.5%); 2) acquired immunodeficiency syndrome (AIDS)-related complex (26 patients, 19.1%); 3) AIDS (93 patients, 68.4%). RESULTS: During a mean follow-up period of 415 +/- 220 days, seven patients, all in the AIDS subgroup, developed clinical and echocardiographic findings of acute global left ventricular dysfunction; of these, six (85%) died of congestive heart failure. Mean survival time from symptom onset was 41 +/- 13 days. Necropsy findings in five patients revealed acute lymphocytic myocarditis in three, cryptococcal myocarditis in one and interstitial edema and fibrosis in one. In only one patient was left ventricular dysfunction reversible with treatment. CONCLUSIONS: Although infrequent, acute global left ventricular dysfunction is not rare in the course of HIV infection. It seems to occur exclusively during the AIDS stage. Acute global left ventricular dysfunction is often fatal but may be reversible and is mainly associated with the pathologic findings of acute myocarditis.

AIDS-Related Complex↗

Absence of a deleterious effect of calcium channel blockers in patients with left ventricular dysfunction after myocardial infarction: The SAVE Study Experience. SAVE Investigators. Survival and Ventricular Enlargement.

BACKGROUND: As a result of randomized controlled trials with calcium channel blockers after myocardial infarction, concern has developed that these agents are associated with an increased risk of cardiovascular events, particularly in the presence of left ventricular dysfunction. METHODS: To test the hypothesis that calcium channel blockers increase cardiovascular events in such patients, the incidence of all-cause mortality, cardiovascular death, severe heart failure, and recurrent infarction was examined in 940 patients taking calcium channel blockers and 1180 not taking them 24 hours before randomization to placebo or captopril in the Survival and Ventricular Enlargement (SAVE) Trial. All patients had an ejection fraction < or =40%. Relative risks for calcium channel blocker users versus nonusers and the 95% confidence intervals were computed with univariate and multivariate Cox regressions. Adjustments were made for differences in baseline covariates. RESULTS: For all causes of mortality, the relative risk for calcium channel blocker users versus nonusers was 0.96, with the 95% confidence interval of 0.78 to 1.17. In the SAVE placebo and captopril groups, the relative risks for the development of severe heart failure among the calcium channel block users versus nonusers were 0.95 and 1.23, with the 95% confidence interval of 0.72 to 1.25 and 0.88 to 1.71, respectively. A similar neutral result held for patients with and without a history of hypertension. Furthermore, calcium channel blockers did not alter the benefit of the angiotensin converting enzyme inhibitor, captopril. CONCLUSIONS: This analysis of the nonrandomized clinical use of calcium channel blockers in the postmyocardial infarction population with left ventricular dysfunction did not identify either a clinical deterioration or improvement with respect to subsequent cardiovascular events.

Adult↗

Hemodynamic importance of systolic ventricular interaction, augmented right atrial contractility and atrioventricular synchrony in acute right ventricular dysfunction.

To delineate the determinants of right ventricular performance with acute right ventricular dysfunction, surgical electrical isolation of the right ventricular free wall was produced in 13 dogs. During atrioventricular (AV) pacing, hemodynamic and wall motion measurements were normal. When not paced, the right ventricular free wall became asystolic, resulting in a depressed and bifid right ventricular systolic pressure (33 +/- 5 to 18 +/- 4 mm Hg) and decreased left ventricular systolic pressure (100 +/- 18 to 80 +/- 18 mm Hg) and stroke volume (14 +/- 4 to 10.3 +/- 3.5 ml) (all p less than 0.05). Ultrasound demonstrated right ventricular free wall dyskinesia, increased right ventricular end-diastolic size (155 +/- 13% of control), but decreased left ventricular size (69 +/- 11% of control) (both p less than 0.05). Right atrial pressure increased (5.8 +/- 2.5 to 7.6 +/- 2.8 mm Hg, p less than 0.05) with an augmented A wave and blunted Y descent, indicating pandiastolic right ventricular dysfunction. The septum demonstrated reversed curvature in diastole and bulged paradoxically into the right ventricle during early systole, generating the initial peak of right ventricular pressure and reducing its volume. Later, posterior septal motion coincided with maximal left ventricular pressure and the second peak of the right ventricular waveform. Left ventricular pacing alone led to further decreases in right ventricular systolic pressure and size, left ventricular systolic pressure and stroke volume. The previously augmented A wave was replaced by a prominent V wave. Therefore, when contractility of its free wall is acutely depressed, right ventricular performance is dependent on left ventricular-septal contractile contributions transmitted by the septum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coronary artery bypass surgery in patients with left ventricular dysfunction.

The effects of coronary artery bypass surgery in patients with left ventricular dysfunction (left ventricular ejection fraction of less than 45 percent) on survival, symptoms, left ventricular ejection fraction, and regional left ventricular function were prospectively assessed in 34 patients. Left ventricular function was serially assessed by nuclear angiocardiography. Operative mortality was 9 percent, and mortality during the follow-up period was 10 percent. Twenty of 21 patients with class III or IV anginal symptoms preoperatively improved by at least two functional classes. Seven of 10 patients with class III or IV symptoms of heart failure preoperatively improved by at least one functional class. Global left ventricular ejection fraction improved significantly with surgery (p less than 0.05). Regional left ventricular systolic function improved as well (p less than 0.005). These findings suggest that in selected patients with left ventricular dysfunction, coronary artery bypass surgery can be performed with acceptable mortality and may result in symptomatic and functional benefit.

Adult↗

Effect of inotropic and vasodilator therapy on left ventricular diastolic filling in dogs with severe left ventricular dysfunction.

Inotropic and vasodilator therapy for congestive heart failure improve left ventricular systolic performance by different mechanisms. However, the nature and extent to which diastolic filling is altered have not been well described. Acute severe left ventricular dysfunction was induced in 21 dogs by severe left ventricular global ischemia produced by left main coronary artery microsphere embolization until left ventricular end-diastolic pressure was greater than or equal to 18 mm Hg. Dobutamine was infused in seven dogs until the peak positive first derivative of left ventricular pressure (dP/dt) increased by greater than or equal to 33%. Nitroprusside was infused in seven dogs until left ventricular end-diastolic pressure was less than 15 mm Hg. Seven dogs were observed for 1 h after the induction of acute severe left ventricular dysfunction and served as the control group. In all groups of dogs, severe left ventricular dysfunction resulted in left ventricular dilation, reduction in area ejection fraction, elevation of left ventricular end-diastolic pressure and an early redistribution of diastolic filling (increased 1/3 and 1/2 filling fractions) despite a markedly abnormal time constant of relaxation. No changes were noted in any variable after 1 h of observation in the seven control dogs. Nitroprusside reduced left ventricular size and filling pressure, increased cardiac output, improved relaxation and redistributed diastolic filling to later in diastole as characterized by a reduced 1/3 filling fraction (19.4 +/- 7.4% versus 51.4 +/- 10%, p less than 0.001). The pressure-area curve was shifted downward and leftward.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mortality and morbidity after mitral valve repair: the importance of left ventricular dysfunction.

A retrospective study of 219 consecutive patients who underwent mitral valve repair for mitral regurgitation or mixed mitral valve disease with at least moderate regurgitation was undertaken. The etiology was degenerative in 151 (68.9%) patients, endocarditis in 24 (10.9%), rheumatic in 22 (10.0%), ischemic in 13 (5.9%), congenital in five (2.3%) and cardiomyopathy in two (0.9%). The average age was 64.8 +/- 10.9 years, the average follow up 30.2 +/- 24.1 months. Pre-operatively, 74% were in NYHA functional class III or IV. Left ventricular function was assessed by angiography and echocardiography, and moderate or severe impairment (ejection fraction < or = 40%) was assumed to represent significant left ventricular dysfunction. There were six (2.7%) hospital deaths, four of which were due to left ventricular dysfunction. The seven-year mortality and seven-year combined mortality and morbidity were 14.4% and 37.1% respectively for complications related to left ventricular dysfunction, and 2.5% and 24.2% respectively for unrelated complications. Subgroup analysis showed that five-year mortality and five-year combined mortality and morbidity due to left ventricular dysfunction were significantly worse in patients who had pre-operative left ventricular dysfunction than those who did not: 28.5% vs. 6.1% (p < 0.001) and 52.4% vs. 17.8% (p < 0.001). There was nevertheless a significant incidence of postoperative left ventricular dysfunction in patients with satisfactory preoperative left ventricular function. In this group, five-year mortality and five-year combined mortality and morbidity due to left ventricular dysfunction were higher in patients who were in NYHA class III or IV preoperatively than in those who were not: 11.2% vs. 0% (NS) and 25.9% vs. 0% (p < 0.01) respectively, particularly if they also had early (3-10 days) post-operative left ventricular dysfunction: 20.4% (p < 0.001) and 41.7% (p < 0.001) respectively. Despite preservation of the mitral apparatus, left ventricular dysfunction remains a major cause of mortality and morbidity following mitral valve repair for mitral regurgitation.

Adolescent↗

Ergometric exercise testing and sensitivity of cyclic guanosine 3',5'-monophosphate (cGMP) in diagnosing asymptomatic left ventricular dysfunction.

OBJECTIVE: Increased plasma concentrations of cyclic guanosine monophosphate (cGMP) have been reported in patients with manifest heart failure. At rest, however, cGMP concentrations in patients with asymptomatic left ventricular dysfunction or heart failure in New York Heart Association (NYHA) functional class I do not differ significantly from those of healthy subjects. The purpose of this study was to investigate whether graded exercise on an ergometer improves the sensitivity of cGMP in diagnosing asymptomatic left ventricular dysfunction. PATIENTS: Plasma cGMP concentrations were compared in 17 healthy controls and 98 patients with asymptomatic left ventricular dysfunction or congestive heart failure of different stages (asymptomatic left ventricular dysfunction or NYHA functional class I, 56 patients; NYHA class II, 31 patients; NYHA class III, 11 patients). RESULTS: Before exercise plasma cGMP concentrations in patients with clinical heart failure (NYHA functional classes II and III) were significantly higher than those in healthy controls. In patients with asymptomatic left ventricular dysfunction or heart failure of functional class I plasma cGMP concentrations were not significantly different from those in healthy subjects. Thirty minutes after exercise, however, cGMP concentrations in patients with asymptomatic left ventricular dysfunction or class I heart failure were significantly higher than those in healthy controls. CONCLUSION: Measurement of plasma cGMP concentrations 30 minutes after ergometric exercise testing allows better discrimination between healthy subjects and patients with symptomless left ventricular dysfunction or mild heart failure (NYHA class I) than measurement of such concentrations before exercise.

Adult↗

From left ventricular dysfunction to heart failure.

Although there is undoubtedly a link between ventricular dysfunction and heart failure the interrelationship is complex. Most patients with left ventricular dysfunction die before progression to heart failure. Heart failure is not preceded by a period of chronic left ventricular dysfunction for the large number of patients who develop heart failure soon after a myocardial infarction. Atrial fibrillation and myocardial ischaemia/infarction need to be considered as mechanisms of progression as well as left ventricular remodelling. ACE inhibitors and beta-blockers, but not diuretics or digoxin, may alter progression to and of heart failure. Potential adverse effects of aspirin on prognosis in patients with heart failure and coronary artery disease are cause for considerable concern.

Adrenergic beta-Antagonists↗

The semi-elective use of the pulmonary artery flotation catheter in children with progressive pulmonary hypertension or left ventricular dysfunction.

OBJECTIVE: To describe the experience with the semi-elective use of the pulmonary artery flotation catheter in pediatric patients with progressive pulmonary hypertension or left ventricular dysfunction. DESIGN: Prospective study. SETTING: Pediatric intensive care unit in a tertiary care center. PATIENTS: Seven consecutive children with pulmonary hypertension and ten children with left ventricular dysfunction. INTERVENTIONS: Drug-response studies were performed using a pulmonary artery flotation catheter. Cardiac index, systemic and pulmonary blood pressure, and occlusion pressure were measured during incremental doses of calcium channel blocker (diltiazem) that were administered to children with pulmonary hypertension and during incremental doses of nitroglycerine and angiotensin-converting enzyme-inhibitor (captopril) that were administered to patients with left ventricular dysfunction. MAIN RESULTS: Four patients (60%) with pulmonary hypertension were identified as responders to calcium channel blockers, resulting in maintenance therapy with high-dose diltiazem in three of them. Nine patients (90%) with left ventricular dysfunction showed a >15% increase in cardiac index with vasodilator therapy. Eleven patients (65%) developed fever during the procedure. Nine patients (53%) had a high probability of bacterial infection. Seven patients (40%) died within 3.5 months after the procedure. Fever, infection, and mortality appeared to occur more frequently in patients in New York Heart Association classes III and IV. CONCLUSIONS: The use of a pulmonary artery flotation catheter enables us to optimize medical treatment strategies in the individual child with progressive pulmonary hypertension or left ventricular dysfunction. Children with left ventricular dysfunction in poor clinical condition showed a high mortality rate post or propter the procedure. In our opinion, drug-response studies using pulmonary artery flotation catheters in patients with left ventricular dysfunction should be performed in a relatively early stage of the disease.

Journal Article↗

Left ventricular dysfunction resulting from frequent unifocal ventricular ectopics with resolution following radiofrequency ablation.

A case is presented, in which asymptomatic but persistent right ventricular outflow tract (RVOT) ectopics resulted in left ventricular (LV) dilatation and systolic dysfunction. The patient underwent extensive investigation with no other cause for the cardiomyopathy being found. Successful ablation of the RVOT ectopic focus resulted in normalization of LV size and function. This case suggests that frequent ventricular ectopy should be considered as a potentially remediable cause of LV dysfunction.

Adult↗

Surgical survival benefits for coronary disease patients with left ventricular dysfunction.

Controversy still exists about the proper selection of patients with coronary artery disease and left ventricular dysfunction for coronary bypass surgery. To examine this issue, we studied 710 patients with significant coronary artery disease and left ventricular dysfunction (ejection fraction less than or equal to 40%). Of 301 patients treated surgically, 232 had bypass grafts; 17, left ventricular surgery; and 52, both procedures. At 3 years after treatment, unadjusted survival was 84% for surgical patients and 64% for medical patients. At baseline, medical patients had more left ventricular dysfunction than surgical patients, but surgical patients had more coronary artery disease and angina than medical patients. In Cox survival models, two invasive factors (ejection fraction and extent of coronary artery disease) and three noninvasive indexes (assessment of myocardial infarction, angina, and conduction disturbances) were the five best predictors of survival (p less than 0.001). After adjustment for these factors between the two treatment groups, overall surgical survival at 3 years after treatment was 86%, and medical survival was 68%. Long-term surgical survival benefits appeared greatest in patients with the most severe left ventricular dysfunction, most extensive coronary artery disease, and most severe anginal symptoms. We conclude that surgery provides significant survival benefits for coronary disease patients with left ventricular dysfunction; in general, the sicker the patient, the greater the benefit.

Angina Pectoris↗

Determinants of ventricular arrhythmias in mildly symptomatic patients with coronary artery disease and influence of inducible left ventricular dysfunction on arrhythmia frequency.

To determine the relation among ventricular arrhythmias, prognostic factors and reversible ischemia in coronary artery disease, 131 drug-free, minimally symptomatic patients were studied by radionuclide angiography and 24 hour Holter electrocardiographic monitoring. High grade ventricular arrhythmias (couplets, salvos of premature ventricular complexes and R on T phenomenon) were observed in 33 patients (25%) and were related to lower rest and exercise ejection fraction, greater number of stenotic coronary arteries and higher prevalence of regional wall motion abnormalities at rest (all p less than or equal to 0.1). Among patients with subnormal rest ejection fraction, high grade arrhythmias occurred with greater prevalence in those with reversible left ventricular dysfunction (reduction in ejection fraction) during exercise compared with those with a normal ejection fraction response (59 versus 23%, p less than 0.05), a relation observed principally in patients with multivessel disease. These data indicate that in minimally symptomatic patients with coronary artery disease, arrhythmias are related to both extent of disease and severity of regional and global ventricular dysfunction and are most prevalent in patients with ventricular dysfunction and evidence of inducible ischemia, factors indicating poor long-term prognosis during medical therapy.

Adult↗

Initial blood pressure response to enalapril in hospitalized patients (Studies of Left Ventricular Dysfunction [SOLVD]).

Studies of Left Ventricular Dysfunction (SOLVD) is a randomized trial of enalapril versus placebo in reducing mortality in patients with cardiac dysfunction (defined as left ventricular ejection fraction less than or equal to 35%). Before randomization, patients at risk for hypotension were hospitalized for a test dose of 2.5 mg of enalapril administered orally at baseline and again 12 hours later. As of February 1989, 89 of 7,539 (1.2%) patients had been studied during hospitalization. Baseline systolic and diastolic blood pressures were 115 +/- 18 and 73 +/- 10 mm Hg, respectively. After enalapril, systolic blood pressure decreased slightly but significantly 8 to 20 hours after the initial dose (mean reduction 8 to 11 mm Hg). In this highly selected group of 89 patients, symptoms relating to decrease in blood pressure were noted in 13 (15%). It is emphasized that most patients with cardiac dysfunction readily tolerate enalapril. However, the agent should be administered with caution to patients with advanced congestive failure and diminished baseline blood pressure, owing to a significant incidence of symptomatic hypotension.

Aged↗

Prevalence and clinical characteristics of left ventricular dysfunction among elderly patients in general practice setting: cross sectional survey.

OBJECTIVE: To assess the prevalence and clinical characteristics of left ventricular dysfunction among elderly patients in the general practice setting by echocardiographic assessment of ventricular function. DESIGN: Cross sectional survey. SETTING: Four centre general practice in Poole, Dorset. SUBJECTS: 817 elderly patients aged 70-84 years. MAIN OUTCOMES: Echocardiographic assessment of left ventricular systolic function including measurement of ejection fraction by biplane summation method where possible, clinical symptoms, and signs of left ventricular dysfunction. RESULTS: The overall prevalence of left ventricular systolic dysfunction was 7.5% (95% confidence interval 5.8% to 9.5%); mild dysfunction (5.0%) was considerably more prevalent than moderate (1.6%) or severe dysfunction (0.7%). Measurement of ejection fraction was possible in 82% of patients (n=667): in patients categorised as having mild, moderate, or severe dysfunction, the mean ejection fraction was 48% (SD 12.0), 38% (8.1), and 26% (7.9) respectively. At all ages the prevalence was much higher in men than in women (odds ratio 5.1, 95% confidence interval 2.6 to 10.1). No clinical symptom or sign was both sensitive and specific. In around half the patients with ventricular dysfunction (52%, 32/61) heart failure had not been previously diagnosed. CONCLUSIONS: Unrecognised left ventricular dysfunction is a common problem in elderly patients in the general practice setting. Appropriate treatment with angiotensin converting enzyme inhibitors has the potential to reduce hospitalisation and mortality in these patients, but diagnosis should not be based on clinical history and examination alone. Screening is feasible in general practice, but it should not be implemented until the optimum method of identifying left ventricular dysfunction is clarified, and the cost effectiveness of screening has been shown.

Aged↗

Prognostic significance of plasma norepinephrine in patients with asymptomatic left ventricular dysfunction. SOLVD Investigators.

BACKGROUND: Elevated plasma neurohormonal levels are associated with increased mortality rates in patients with symptomatic heart failure. A previous Studies of Left Ventricular Dysfunction (SOLVD) trial suggested that neurohumoral activation precedes the development of symptoms as demonstrated by increased neurohormonal levels in patients with asymptomatic left ventricular dysfunction. However, the significance of this early neurohumoral activation is unclear. The goals of this study were to determine the prognostic significance of the plasma concentrations of plasma norepinephrine (PNE) and atrial natriuretic peptide (ANP) and the renin activity (PRA) in patients with asymptomatic left ventricular dysfunction. METHODS AND RESULTS: PNE and PRA were measured before randomization in 514 patients with left ventricular ejection fractions < or = 35% who did not require treatment for congestive heart failure and were enrolled in the SOLVD Prevention Trial. Plasma ANP levels were measured in a subset of 241 patients owing to study design. Using the Cox proportional hazards model that included left ventricular ejection fraction, New York Heart Association functional class, age, sex, treatment assignment to placebo or enalapril, and cause of heart failure, we examined whether these neurohormones predicted all-cause mortality, cardiovascular mortality, hospitalization for heart failure, development of heart failure, or development of ischemic events (myocardial infarction or unstable angina). PNE was the strongest predictor of clinical events in this patient population. PNE levels above the median of 393 pg/mL were associated with a relative risk of 2.59 (P = .002) for all-cause mortality, 2.55 (P = .003) for cardiovascular mortality, 2.55 (P = .005) for hospitalization for heart failure, 1.88 (P = .002) for development of heart failure, 1.92 (P = .001) for ischemic events, and 2.59 (P = .005) for myocardial infarction. PNE remained the most powerful predictor for all-cause mortality and ischemic events when the analysis included only the patients with histories of ischemic left ventricular dysfunction. The increases in other neurohormonal levels were not useful in predicting the subsequent development of clinical events. CONCLUSIONS: Increased PNE levels in patients with asymptomatic left ventricular dysfunction appear to predict all-cause and cardiovascular mortalities and development of clinical events related to the onset of heart failure or acute ischemic syndromes. Thus, measurement of PNE may be a possible early marker for assessment of disease progression in patients with left ventricular dysfunction, and modulating the release or effect of PNE may lead to improved prognosis and/or a reduction in morbidity.

Angina, Unstable↗

[Doppler flow-velocity analysis of the renal arteries in left ventricular dysfunction].

AIM OF THE STUDY: Chronic heart failure leads to renal hypoperfusion. Clinical methods for monitoring renal artery flow have several limitations. We analyzed the renal artery flow-velocity in patients with left ventricular dysfunction and normal controls by pulsed-wave (PW) color-guided Doppler technique. The relation between PW Doppler quantitative indexes and left ventricular ejection fraction (LVEF), creatinine clearance, and age, was also assessed. METHODS: We studied 53 patients with left ventricular dysfunction (LVEF by 2D echo < or = 40%) and no systemic hypertension, diabetes, parenchymal nephropathy, serum creatinine levels > 150 mmol/l, nor renal artery stenosis. Five patients were excluded for suboptimal renal artery PW Doppler recordings. Thus, the study group was constituted of 48 patients (mean age: 64 +/- 13 years). Twenty-eight normal subjects (mean age: 61 +/- 9 years) were the control group. By PW Doppler we measured the maximum (Vmax), the minimum (Vmin) and the mean (Vmean) velocities of both renal arteries. The resistivity index (RI), obtained from the formula (Vmax-Vmin)/ Vmax, and the pulsatility index (PI), obtained from the formula (Vmax-Vmin)/Vmed were calculated. Creatinine clearance was determined in each patient. RESULTS: RI and PI were greater in patients with left ventricular dysfunction than in normal controls. In normal controls, RI and PI were related to age (r: 0.63, p < 0.001; and r: 0.45, p < 0.05) and creatinine clearance (r: -0.44 and -0.40, respectively; both: p < 0.05), not to LVEF. In patients with left ventricular dysfunction, RI and PI were related to LVEF (r: -0.67 and -0.59; both: p < 0.001), other than to age (r: 0.57 and 0.55; both: p < 0.001) and creatinine clearance (r: -0.59, p < 0.001, and r = -0.46, p < 0.01, respectively). In this group, however, there was no sharp separation of RI and PI between patients with different degree of left ventricular dysfunction (LVEF < or = 30% and > 30%). CONCLUSIONS: In patients with left ventricular dysfunction, by renal artery PW Doppler analysis it is possible to detect noninvasively a reduction in regional flow-velocity and an increase in Doppler-derived vascular resistance indexes. These Doppler changes mainly depend on severity of left ventricular dysfunction and less on age of patients.

Adult↗

Ventricular dysfunction clinical research in infants, children and adolescents.

These two issues of Progress in Pediatric Cardiology comprehensively illustrate the wealth of currently available information on the pathophysiology of heart failure, age-related myocardial responsiveness, energy metabolism, cardiopulmonary interactions, the pressure-volume relationship, the systemic inflammatory response, the management of heart failure, pediatric pharmacology, the use of heart failure therapies including digoxin, ACE inhibitors, beta-adrenergic blockers, inotropic agents, diuretics, vasodilators, calcium sensitizers, angiotensin and aldosterone receptor blockers, growth hormone, and future gene therapy. The etiology and course of ventricular dysfunction in children is poorly characterized. Furthermore, many changing developmental properties of the pediatric myocardium and differences in the etiologies of ventricular dysfunction in children compared with adults are illustrated in these articles, invalidating the concept that children can safely be considered small adults for the purpose of understanding heart failure pathophysiology and treatment. However, these articles reveal that strikingly little research in children with ventricular dysfunction exists in terms of well-designed large-scale studies of the epidemiology or multicenter controlled clinical therapeutic trials. A future research agenda is proposed to improve understanding etiologies, course and treatment of ventricular dysfunction in children that is based on organized and funded cooperative groups since no one pediatric cardiac center treats enough children with a particular etiology of ventricular dysfunction. In conclusion, significant understanding of basic mechanisms of pediatric ventricular dysfunction and effective therapies for adults with ventricular dysfunction exist. A multicenter pediatric cardiac ventricular dysfunction network would allow improved understanding of diseases and treatments, and result in evidence-based medicine for pediatric patients with ventricular dysfunction.

Journal Article↗

Cardiorenal and neurohumoral function in a canine model of early left ventricular dysfunction.

BACKGROUND: Recent studies have reported that asymptomatic left ventricular dysfunction (ALVD) in humans is characterized by early neurohumoral activation. Specifically, atrial natriuretic factor (ANF) and norepinephrine are activated without activation of the renin-angiotensin-aldosterone system (RAAS). The current study describes hemodynamic and renal function associated with this neurohumoral profile in a canine model of early and presumably "asymptomatic" ventricular dysfunction. We hypothesized that the neurohumoral profile observed in ALVD is associated with preservation of renal function despite significant hemodynamic compromise. METHODS AND RESULTS: ALVD was produced by ventricular pacing at 180 beats per minute for 10 days. Intravascular volume expansion was performed before and after producing ALVD in eight conscious dogs. The model of ALVD was characterized by decreases in ejection fraction (48 +/- 2 to 29 +/- 4%), cardiac output (4.64 +/- 0.29 to 2.89 +/- 0.17 L/min), and mean arterial pressure (119 +/- 4 to 108 +/- 4 mm Hg). Atrial pressures and systemic vascular resistance were increased. ANF (60 +/- 19 to 165 +/- 27 pg/mL) and norepinephrine (382 +/- 127 to 690 +/- 211 pg/mL) were activated, whereas the RAAS was not. Creatinine clearance and sodium excretion (UNa V) were unchanged after producing ALVD. The natriuretic response to volume expansion in ALVD was completely intact, with increases in UNa V similar to that observed with volume expansion in ALVD was completely intact, with increases in UNa V similar to that observed with volume expansion before producing ALVD. CONCLUSIONS: The current study demonstrates that significant ventricular dysfunction with peripheral vasoconstriction can be associated with normal renal function and thus suggests an important functional role for the neurohumoral profile of ALVD in preserving sodium balance.

Animals↗