Advanced Left Ventricular Dysfunction Research Articles

Hundred years of atrial fibrillation: Current knowledge and perspectives

Atrial fibrillation (AF) is the most common sustained arrhythmia in general population. AF in humans was first described in 1903. Gradually, it has been well appreciated that AF is notjust an acceptable alternative for normal rhythm but rather a serious threat, related to increased mortality and cardiovascular morbidity. AF can precipitate or worsen pre-existing heart failure, may cause the development of tachycardiomyopathy and is an independent risk factor for thromboembolic events, most frequently stroke. It has long been believed that rhythm control is the best therapy for AF. Nowadays there is a clear scientific proof that rhythm control offers no benefit over frequency control, at least for older patients, even with advanced left ventricular dysfunction. However, optimal treatment for younger, highly symptomatic, otherwise healthy AF patients has not been designed. Available antiarrhythmics have considerable proarrhythmic potential or organ toxicity, and new safer drugs are under investigation. Nonpharmacological approaches, namely RF-catheter ablation, are rapidly developing. Prevention of thromboembolism is imperative, and new safer oral anticoagulants have been intensively investigated. Recent randomized studies (PIAF, RACE, STAF, AFFIRM, HOT-CAFE) did not solve the issue of optimal arrhythmia treatment, but they emphasized the prevention of thromboembolism based on risk factors, and not on AF type, mainly because asymptomatic episodes of AF may not be clinically recognised.

Relationship between mortality of patients with atrial fibrillation and mortality of general population in Serbia

Large population-based observational trials have shown atrial fibrillation (AF) to be an independent risk factor for increased mortality. To examine all-cause mortality and cardiovascular mortality of patients with AF compared to corresponding mortality in general population of Serbia. This longitudinal observational study included patients with nonvalvular AF as the main indication for in-hospital and/or outpatient treatment at the Clinical Centre of Serbia, Belgrade, during the period 1992-2007, if the latest date of the first diagnosed AF was early January 2003, so that the total follow-up could last at least 5 years (minimum 1 year prospectively), or until death. Patients with acute causes of AF, advanced left ventricular systolic dysfunction (LVEF < or = 25%), preexcitation, known malignancy or any advanced chronic disease and patients with poorly documented history of previous AF were not included. To compare mortality of study population with mortality of general population, we used standardized mortality ratio (SMR) and chi-square test, p < 0.05. Out of 1100 patients (389 females, 35.4%), aged 52.7 +/- 12.2 years, with total follow-up 9.94 +/- 6.05 years (prospective 5.75 +/- 4.28, retrospective 4.21 +/- 5.51), 40% had no underlying disease; others most frequently had arterial hypertension. AF was paroxysmal in 665 (60.5%), persistent in 225 (20.5%) and permanent in 210 patients (19.1%). Newly diagnosed AF was documented in 1058 patients (96.2%). Until the end of the study, 85 patients died (7.7%). Cardiovascular death was noted in 62 patients (72.9%), most frequently in form of sudden death (27/85, 31.7%), death from congestive heart failure (18/85, 21.2%) and stroke (14/85, 16.5%). Most patients (67/85, 78.8%) had AF at the time of death. SMR for all-cause mortality was 2.43 (p < 0.0001) and for cardiovascular mortality 3.03 (p < 0.0001). All-cause mortality and cardiovascular mortality of AF patients are higher than corresponding mortality in general population of Serbia, despite active treatment.

A case report of an unusual complication of Amanita phalloides poisoning: Development of cardiogenic shock and its successful treatment with intra-aortic balloon counterpulsation

Amanita phalloides is responsible for the majority of the fatalities caused by mushroom poisoning. It causes damage in liver, kidneys and rarely pancreas, causing encephalopathic coma, disseminated intravascular coagulation, hemorrhage and hypovolemic shock. However, its effect on cardiac functions has not been established yet. In this case report, we aimed to present a female patient poisoned by A. phalloides mushroom complicated with multi-organ failure and cardiogenic shock due to advanced left ventricular systolic dysfunction. This case report was the first to show a successful treatment of cardiogenic shock due to mushroom poisoning with intra-aortic balloon counterpulsation, whereas she did not respond to other therapies.

Impact of mitral valve repair in patients with mitral regurgitation undergoing coronary artery bypass grafting

Objectives: In patients with mitral regurgitation (MR) and advanced left ventricular (LV) dysfunction, it is not clear whether additional mitral valve repair (MVR, replacement or reconstruction) at the time of coronary artery bypass graft surgery is beneficial.

Chronic systemic inflammation accompanies impaired ventricular diastolic function, detected by Doppler imaging, in patients with newly diagnosed systolic heart failure (Hellenic Heart Failure Study)

We sought to evaluate the relationship between plasma cytokine levels (sCD14, tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) and tissue Doppler derived indices of left ventricular systolic and diastolic function in patients with newly diagnosed heart failure. We enrolled 101 consecutive patients (mean age 65+/-13 years) with newly diagnosed heart failure who were hospitalized in our institute. Echocardiographic assessment was performed in all patients during the third day of their initial hospitalization. The pulsed tissue Doppler imaging (TDI) of the systolic and diastolic function of mitral annulus was characterized by the systolic wave Smv, and the diastolic waves: Emv and Amv. Left atrial kinetic energy (LAKE), an index of left atrial function, was calculated using the equation 1/2 x LASV x 1.06 x Amv(2); where LASV is left atrial systolic volume. Furthermore the ratio E/Emv and the flow propagation velocity were also calculated; where E is the rapid mitral filling wave, detected by pulse Doppler. Soluble plasma levels of CD14, TNF-alpha, and IL-6 were measured in all patients during their third day of hospitalization. Linear regression analysis, after adjustment for sex, age, left ventricular ejection function, body mass index, arterial hypertension, smoking, physical activity, creatinine clearance, diabetes mellitus, and blood lipid levels, revealed that IL-6 levels were inversely associated with LAKE (b= - 5422.4+/-2031.5, P=0.03), Sm (b= -0.375+/-0.1, P=0.03), and flow propagation (b= -5.404+/-0.621, P=0.001). CD14 levels were inversely associated with flow propagation (b = -17.655+/-2.6, P=0.001), and positively associated with E/Emv ratio (b=2.58+/-3.6, P=0.002) and A/Amv ratio (b=0.629+/-0.6, P=0.04). TNF-alpha was inversely associated with Smv (b-1.189+/-0.3, P=0.005). This study reveals that increased plasma levels of CD14, IL-6 and TNF-alpha are associated with impaired left atrial function and more advanced left ventricular diastolic and systolic dysfunction, in patients with newly diagnosed heart failure.

PDE5A Inhibitor Treatment of Persistent Pulmonary Hypertension After Mechanical Circulatory Support

Pulmonary hypertension (PH) secondary to left heart failure portends a poor prognosis and is a relative contraindication to heart transplantation at many centers. We tested the hypothesis that when PH persists after adequate left ventricle unloading via recent left ventricular assist device (LVAD) therapy, phosphodiesterase type 5A inhibition would decrease PH in this population. We performed an open-label clinical trial using control patients not receiving therapy. Between 1999 and 2007, 138 consecutive patients undergoing cardiac transplantation evaluation with advanced left ventricular dysfunction, an elevated pulmonary capillary wedge pressure, and PH (defined by a pulmonary vascular resistance (PVR) >3 Woods Units), were treated with LVAD therapy. Fifty-eight of these patients reduced their pulmonary capillary wedge pressure to a value <15 mm Hg (11.8+/-2.0 mm Hg from baseline 23.2+/-6.2 mm Hg) 1 to 2 weeks after LVAD implantation, but despite this improvement, the PVR of these patients was only minimally affected (5.65+/-3.00 to 5.39+/-1.78 Wood Units). Twenty-six consecutive patients from this group with persistently elevated PVR were started on oral phosphodiesterase type 5A inhibition with sildenafil and titrated to an average of dose of 51.9 mg by mouth 3 times per day. The average PVR in the sildenafil-treated group fell from 5.87+/-1.93 to 2.96+/-0.92 Wood Units (P<0.001) and the mean pulmonary artery pressure fell from 36.5+/-8.6 to 24.3+/-3.6 mm Hg (P<0.0001) and was significantly lower when compared with the 32 LVAD recipients not receiving sildenafil at weeks 12 to 15 after the initial post-LVAD hemodynamic measurements (13 to 17 weeks post-LVAD implantation). In addition, hemodynamic measurements of right ventricular function in sildenafil-treated patients was also improved compared with patients not receiving sildenafil. In patients with persistent PH after recent LVAD placement, phosphodiesterase type 5A inhibition in this open-label trial resulted in a significant decrease in PVR when compared with control patients.

Validity of N-terminal propeptide of the brain natriuretic peptide in predicting left ventricular diastolic dysfunction diagnosed by tissue Doppler imaging in patients with chronic liver disease

Left ventricular diastolic dysfunction has been reported in patients with liver cirrhosis. Although conventional Doppler echocardiography has been used to assess diastolic filling dynamics, this technique is limited in diagnosing left ventricular diastolic dysfunction. The aim of the study was to validate the N-terminal propeptide of the brain natriuretic peptide (NT-proBNP) in predicting left ventricular diastolic dysfunction diagnosed by tissue Doppler imaging in patients with chronic liver disease. In 64 patients, left ventricular diastolic dysfunction was classified using tissue Doppler imaging and serum levels of NT-proBNP were measured. Left ventricular diastolic dysfunction was found in 25 of 31 (80.6%) patients with severe liver fibrosis/cirrhosis versus 2 of 8 (25.0%) patients with moderate and 6 of 25 (24.0%) patients with mild liver fibrosis (P<0.001). Mean NT-proBNP levels were 407.1+/-553.4 pg/ml in patients with severe fibrosis/cirrhosis as compared with 60.8+/-54.9 pg/ml and 55.4+/-41.4 pg/ml in patients with mild and moderate fibrosis (P=0.001). NT-proBNP was most accurate in predicting advanced left ventricular diastolic dysfunction with an area under the receiver-operating characteristic curve of 0.90 (95% confidence interval, 0.77-1.0; P<0.001). A cutoff value of greater than 290 pg/ml was highly predictive of advanced left ventricular diastolic dysfunction. NT-proBNP is a useful marker in detecting advanced left ventricular diastolic dysfunction in patients with chronic liver disease. Patients with severe liver fibrosis/cirrhosis and NT-proBNP levels exceeding 290 pg/ml should undergo further cardiac evaluation.

Hemodynamic changes before acute heart failure episodes in patients with advanced systolic left ventricular dysfunction

We sought to verify which changes in right ventricular pressures occur before acute heart failure (HF) in patients with advanced systolic left ventricular (LV) dysfunction. In patients with chronic HF, continuous hemodynamic monitoring by implantable devices may detect increases in pulmonary pressures before the onset of symptoms. A device which allowed monitoring of right ventricular systolic (RVSP) and diastolic pressure (RVDP) and an estimate of pulmonary artery diastolic pressure (ePAD) was implanted in 10 patients with advanced LV systolic dysfunction and frequent cardiovascular hospitalizations [mean age 56.8 years; New York Heart Association (NYHA) classes IIIb-IV; LV ejection fraction at echocardiography 21 +/- 2%]. During a follow-up period of 15 +/- 12 months, 18 hospitalizations due to acute HF were recorded; 10 episodes were characterized by symptoms due to low-cardiac output (LCO) and eight episodes were characterized by symptoms due to pulmonary congestion. RVSP and ePAD increased before six hospitalizations and decreased before three episodes; RVDP increased before 10 hospitalizations and decreased before one. The extent of RVDP increase was 16 +/- 24% before pulmonary congestion episodes and 29 +/- 32% before LCO episodes. An increase in RVDP was the most frequent hemodynamic change detected by the implantable hemodynamic monitor before hospitalizations due to acute HF in patients having advanced systolic LV dysfunction.

Risk stratification of patients with prior myocardial infarction and advanced left ventricular dysfunction by gated myocardial perfusion SPECT imaging

The Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) has shown that the prophylactic implantable cardiac defibrillator improves the survival rate of patients with prior myocardial infarction and advanced left ventricular (LV) dysfunction. However, a more accurate noninvasive predictor should be found to identify subgroups at high risk, one that would allow implantable cardiac defibrillator therapy to be directed specifically to the patients who would benefit most. To elucidate whether technetium 99m tetrofosmin electrocardiogram-gated single photon emission computed tomography (SPECT) imaging at rest can determine the risk of arrhythmic death, 106 patients who met the MADIT-II criteria (LV ejection fraction <or=0.3, myocardial infarction >1 month earlier, and no sustained ventricular tachyarrhythmia) were recruited from a pool of 4628 consecutive patients who had undergone resting Tc-99m tetrofosmin SPECT imaging. By use of the endpoints of lethal arrhythmic events, which included documentation of sustained ventricular tachycardia, ventricular fibrillation, or diagnosis of sudden cardiac death, we performed follow-up for a mean of 30 months. Lethal arrhythmic events occurred in 14 patients. Patients with lethal arrhythmic events had a lower LV ejection fraction, greater LV end-systolic and end-diastolic volume indices, and a greater perfusion defect volume than the remaining patients. By receiver operating characteristic curve analysis, myocardial defect volume was the strongest predictor for the development of lethal arrhythmic events. Our results confirm that perfusion defect volume by Tc-99m tetrofosmin scintigraphy is the most pivotal predictor of the future occurrence of lethal arrhythmic events and of sudden cardiac death. Tc-99m tetrofosmin SPECT images may assist in identifying subsets of patients with a greater likelihood of arrhythmic death among patients with LV dysfunction.

Impact of Myocardial Function on Cystatin C Measurements in Chronic Systolic Heart Failure

Background The influence of myocardial function on plasma levels of cystatin C (CysC), a sensitive marker of renal function, in chronic systolic heart failure (HF) has not been well established. Methods We prospectively identified 139 subjects with stable, chronic HF (left ventricular ejection fraction ≤ 35%) and measured plasma levels of CysC. We prospectively tracked patients' long-term adverse clinical outcomes (death, cardiac transplantation, and HF hospitalizations). Results Plasma levels of CysC were elevated in 41% of patients with preserved renal function and directly correlated with N-terminal prohormone brain natriuretic peptide ( r = 0.57, P < .0001). There was a significant association between CysC and mitral E/septal E' ratio ( r = 0.34, P < .001), right ventricular systolic dysfunction severity ( r = 0.30, P < .001), and mitral regurgitation severity ( r = 0.31, P < .001), but not left ventricular ejection fraction. At the cutoff of 1.23 mg/dL, CysC remains a significant independent risk factor for adverse clinical outcomes (hazard ratio 1.88, 95% confidence interval 1.15–3.09, P = .012) after adjusting for estimated glomerular filtration rate, left ventricular ejection fraction, and E/septal E'. Conclusion CysC is associated with more advanced left ventricular diastolic dysfunction and right ventricular systolic dysfunction and remains an independent predictor of long-term prognosis in chronic systolic HF after adjusting for myocardial factors.

Mechanical dyssynchrony and functional mitral regurgitation: pathophysiology and clinical implications

Functional mitral regurgitation (FMR) is a common finding in patients with ischemic or nonischemic dilated cardiomyopathy as a complication of left ventricular (LV) dysfunction and remodeling associated with a fibrotic remodeling response of mitral leaflets to abnormal valvular loading. Although mitral valve tenting is the main determinant of FMR, clinical and experimental observations suggest that intraventricular delay could be a potential co-determinant of FMR. LV dyssynchrony can potentially contribute to FMR by several mechanisms, such as creating an uncoordinated regional LV mechanical activation in segments supporting the papillary muscles, determining diastolic mitral regurgitation, reducing the sphincteric function of the mitral annulus, and decreasing the efficiency of LV contraction and closing forces. Cardiac resynchronization therapy has been demonstrated to reduce FMR with correction of some of the underlying pathophysiological mechanisms. The present review article focuses on the role of mechanical dyssynchrony as a pathophysiological determinant of FMR, and on the potential role of cardiac resynchronization therapy as a therapeutic option for treatment of FMR in patients with severe heart failure and advanced LV dysfunction.

Prognostic Value of Location and Type of Myocardial Infarction in the Setting of Advanced Left Ventricular Dysfunction

Location (anterior) and type (Q wave) of myocardial infarction (MI) might be considered of prognostic significance when predicting mortality. However, there are limited data regarding the prognostic significance of type and location of MI in patients with severely depressed left ventricular function. In 1,221 patients in the MADIT II, Q-wave MI was observed in 763 patients (62%), 115 (10%) had non-Q-wave MI, and 343 (28%) had conduction abnormalities. In patients with Q-wave MI, anterior MI was present in 430 (57%), inferior in 155 (20%), and combined in 178 (23%) patients. Study end points included all-cause mortality, hospitalization or death due to worsening congestive heart failure, and episodes of ventricular tachycardia or ventricular fibrillation requiring implantable cardioverter-defibrillator therapy. In a multivariate Cox proportional hazard model predicting mortality, the following clinical variables entered the predictive model at a p value <0.10: treatment (implantable cardioverter-defibrillator vs conventional therapy), age dichotomized at 65 years, angina pectoris, ejection fraction dichotomized at 25%, serum urea nitrogen dichotomized at 25 mg/dl, and beta-blocker use. After adjustment for these covariates, risk of mortality was not significantly different in non-Q-wave MI versus Q-wave MI. However, when analyzing location of MI, inferior wall MI was associated with a significantly (hazard ratio 1.58, p = 0.048) higher risk of mortality than anterior wall MI. In addition, patients with conduction abnormalities had a higher risk of mortality (hazard ratio 1.36, p = 0.088) than patients with anterior wall MI. In conclusion, in the setting of severely depressed ejection fraction (< or =30%), inferior wall MI was associated with a significantly higher risk of mortality than anterior wall MI.

Myocardial Viability Testing and the Effect of Early Intervention in Patients With Advanced Left Ventricular Systolic Dysfunction

Myocardial Viability Testing and the Effect of Early Intervention in Patients With Advanced Left Ventricular Systolic Dysfunction

Clinical Profile and Natural History of 453 Nonsurgically Managed Patients With Severe Aortic Stenosis

Severe aortic stenosis (AS) is a surgically correctable condition. However, aortic valve replacement (AVR) is not offered to many patients with severe AS for various reasons. We investigated the profile and survival patterns of patients with severe AS who did not have AVR. Our echocardiographic database was screened for patients with severe AS, defined as a Doppler estimated aortic valve area of 0.8 cm2 or less between 1993 and 2003. Seven hundred and forty patients with severe AS were identified, of whom 453 patients had no AVR through the follow-up period, forming the study cohort. These patients were comprehensively characterized by obtaining clinical, pharmacologic, and surgical data through a comprehensive chart review and extracting survival data from the National Death Index. Patient characteristics were as follows: age 75 +/- 13 years, 48% male, left ventricular (LV) ejection fraction 52 +/- 21%, coronary artery disease in 34%, hypertension in 35%, serum creatinine level greater than 2 mg/dL in 11%, and diabetes mellitus in 14%. The survival at 1 year, 5 years, and 10 years was 62%, 32%, and 18%, respectively. The univariate predictors of reduced survival were advanced age, low LV ejection fraction, heart failure, elevated serum creatinine level, severe mitral regurgitation, and pulmonary hypertension; and the independent predictors were advanced age, low LV ejection fraction, heart failure, elevated serum creatinine level, and systemic hypertension. Concomitant pharmacotherapy had no impact on survival. Conservatively treated patients with severe AS have a grave prognosis, and it is worse in the presence of advanced age, LV dysfunction, heart failure, and renal failure.

Tei index and neurohormonal activation in patients with incident heart failure: Serial changes and prognostic value

Natriuretic peptides and Tei index are useful indices for risk stratification in advanced left ventricular dysfunction (LVD). Their role in early stages is less clear. In relation to first diagnosis of LVD to assess the relation of plasma B-type-natriuretic peptide (NT-proBNP) with Tei index, assess serial changes in indices, and to assess the value of indices to predict functional status. Doppler echocardiography and neurohormonal analysis were performed (n=150). NYHA class was registered. Tei index correlated with p-NT-proBNP (r=0.75, p<0.0001), and changes in indices correlated (r=0.36, p=0.001) in LVD (n=80). No functional improvement (n=47) was related to a median increase in Tei index (-0.2, -0.16; 0.09); an improvement (n=31) to a reduction (0.06; -0.19; 0.35), p=0.02. In the group with functional improvement, more patients had >/=30% reduction in p-NT-proBNP (75% vs. 45%, p<0.01). Addition of NT-proBNP or Tei index to a clinical model, of no functional improvement, improved log-likelihood chi(2) from 9.32 to 20.18 (p=0.001) and 20.67 (p=0.001). Tei index and p-NT-proBNP demonstrated a fair correlation. Unimproved NYHA class was related to progressive LVD and might be identified by monitoring Tei index or p-NT-proBNP. Advanced LVD and high pre-treatment p-NT-proBNP levels indicated a potential of improvement in functional status.

Cardiac Function and Heart Failure

Background: There is scant data regarding methods to identify subjects in the community with preclinical left ventricular (LV) systolic and diastolic dysfunction. Methods: A population-based sample of 1229 older adults underwent examination with transthoracic echocardiography and measurement of circulating aminoterminal pro-Btype natriuretic peptide (N-BNP) levels. Heart failure status was ascertained according to past history and clinical examination. The ability of N-BNP to detect preclinical LV ejection fraction (EF) <=40% and/or moderate-severe LVDD in the entire cohort and a high-risk subset (hypertension, diabetes and/or coronary disease) was assessed using age/gender-specific optimal discriminatory levels. Results: Of the 1150 subjects (48.9% men; mean age 69.2 years) without prior history or current clinical evidence of congestive heart failure, 71 subjects (6.2%; 95%CI 4.9- 7.7%) had evidence of preclinical advanced LV dysfunction, of which 6 (0.5%; 95%CI 0.2-1.1%) had an EF<=40%.The overall N-BNP performance to identify subjects with preclinical EF<=40% and/or moderate-severe DD was good (AUC 0.83-0.91). However, given the relatively low prevalence of preclinical disease and characteristics of the test, 41-74% of subjects identified with N-BNP screening would have “negative” confirmatory echocardiograms at the expense of missing 9-22% of cases (Table). Conclusions: N-BNP performs well as a marker of LV dysfunction, but its screening utility is limited in the community.

Effects of nebivolol in elderly heart failure patients with or without systolic left ventricular dysfunction: results of the SENIORS echocardiographic substudy

The SENIORS trial recently demonstrated that nebivolol reduces the composite risk of all-cause mortality and cardiovascular hospital admission in elderly patients with chronic heart failure and, importantly, that ejection fraction does not influence the clinical effects of nebivolol. An echocardiographic substudy was designed to evaluate the effects of nebivolol on systolic and diastolic left ventricular (LV) function in patients stratified according to the presence or absence of systolic LV dysfunction. The substudy randomized 112 patients in 29 European centres, of whom 104 were evaluable for the study; 43 had an ejection fraction (EF) <or=35% and 61 had an EF>35%. LV end-systolic volume (ESV), EF, mitral valve E/A ratio, and E-wave deceleration time were assessed at baseline and after 12 months. Echocardiograms were submitted to a core laboratory to perform quantitative analysis in blinded condition. In the group with EF</=35%, nebivolol reduced ESV (adjusted difference between treatments 25.8 mL, 95%CI: -46.6; -5.0, P=0.016) and improved EF (adjusted difference between treatments 4.6%, 95%CI: 1.3;7.9, P=0.008); no changes were observed in the E/A ratio or E-wave deceleration time. In EF>35% group, no significant changes in either systolic or diastolic parameters were observed. In patients with heart failure and advanced systolic LV dysfunction, nebivolol reduces ventricular size and improves EF. The absence of detectable changes with standard echocardiography in patients with predominant diastolic heart failure questions the mechanism of benefit on morbidity/mortality in such patients.

Comparison of Presence and Extent of Coronary Narrowing in Patients With Left Bundle Branch Block Without Diabetes Mellitus to Patients With and Without Left Bundle Branch Block But With Diabetes Mellitus

We prospectively analyzed the clinical, echocardiographic, and coronary arteriographic data of 51 patients with type 2 diabetes mellitus with left bundle branch block (LBBB), 51 patients with type 2 diabetes mellitus without LBBB, and 51 patients with isolated LBBB matched for age and gender. Extent of coronary artery disease (CAD) was classified according to the standard method into 1-, 2-, or 3-vessel disease and was estimated by calculation of the Gensini score. The left ventricular ejection fraction was analyzed by echocardiography. Age, gender, and percentage of patients with a smoking habit or family history of CAD did not differ among the groups. The rates of hypertension and levels of serum creatinine, cholesterol, and triglycerides were statistically higher in group I compared with the other 2 groups. Patients with diabetes and LBBB (group I) had significantly higher scores for the severity (Gensini score) of CAD (p <0.001) and more 3-vessel disease (p <0.001). After adjustment for hypertension, hypertriglyceridemia, and hypercholesterolemia with covariance analysis, the presence of LBBB was also associated with a higher Gensini score in patients with diabetes compared with those with diabetes but without LBBB and those with isolated LBBB (p <0.001). The present study, for the first time, has shown that patients with type 2 diabetes mellitus and concomitant LBBB have more severe and extensive CAD and advanced left ventricular dysfunction compared with those with diabetes but without LBBB and those with isolated LBBB.

The Utility of Pulsed Tissue Doppler Parameters for the Diagnosis of Advanced Left Ventricular Diastolic Dysfunction

The evaluation of diagnostic value of pulsed tissue Doppler (TD) parameters (calculated from six points of mitral annulus and separately measured in the lateral part of mitral annulus) for the detection of pseudonormal mitral inflow pattern. Among 200 persons examined by transthoracic echocardiography group with E/A value between 1 and 2 was selected and divided to normal (54 subjects, early wave deceleration time, Edt > or = 150 msec) and pseudonormal (23 patients, Edt < 150 msec together with prolonged difference between duration of atrial reversal flow in pulmonary vein and mitral flow in atrial phase, delta Ar > or = 20 msec) inflow. Wide spectrum of TD parameters was compared between the selected groups. In normal inflow, average peak velocities of early and atrial phase of diastolic mitral annulus motion were significantly higher: 11.0 +/- 2.6 versus 8.9 +/- 3.5 cm/sec; (P = 0.005) and 12.0 +/- 2.2 versus 10.0 +/- 3.0 cm/sec; (P = 0.002), respectively. Ratio of peak early mitral wave velocity to peak velocity of annulus motion in early phase (Ev/E'v avr) was higher in the pseudonormal pattern: 9.8 +/- 3.7 versus 7.0 +/- 2.0, respectively (P < 0.001). For the value of Ev/E'v avr > 10.2, 70% accuracy for the diagnosis of pseudonormalization was detected. For the parameters measured in the lateral part of mitral annulus similar relationships in the early filling phase were detected but did not reach statistical significance in the atrial phase. Pulsed TD offers good accuracy for the diagnosis of pseudonormalization with increased ratio of peak early mitral wave velocity to peak velocity of mitral annulus being the optimal predictor of advanced diastolic dysfunction.

Myocardial Viability Testing and the Effect of Early Intervention in Patients With Advanced Left Ventricular Systolic Dysfunction

The clinical value of revascularization and other procedures in patients with severe systolic heart failure is unclear. It has been suggested that assessing ischemia and viability by positron emission tomography (PET) with fluorodeoxyglucose (FDG) imaging may identify patients for whom revascularization may lead to improved survival. We performed a propensity analysis to determine whether there might be a survival advantage from revascularization. We analyzed the survival of 765 consecutive patients (age 64+/-11 years, 80% men) with advanced left ventricular systolic dysfunction (ejection fraction < or =35%) and without significant valvular heart disease who underwent PET/FDG study at the Cleveland Clinic between 1997 and 2002. Early intervention was defined as any cardiac intervention (surgical or percutaneous) within the first 6 months of the PET/FDG study. In the entire cohort, 230 patients (30%) underwent early intervention (188 [25%] had open heart surgery, most commonly coronary artery bypass grafting, and 42 [5%] had percutaneous revascularization); 535 (70%) were treated medically. Using 39 demographic, clinical and PET/FDG variables, we were able to propensity-match 153 of the 230 patients with 153 patients who did not undergo early intervention. Among the propensity-matched group, there were 84 deaths during a median of 3 years follow-up. Early intervention was associated with a markedly lower risk of death (3-year mortality rate of 15% versus 35%, propensity adjusted hazard ratio 0.52, 95% CI 0.33 to 0.81, P=0.0004). Among systolic heart failure patients referred for PET/FDG, early intervention may be associated with improved survival irrespective of the degree of viability.