Antiarrhythmic effects of ranolazine used both alone for prevention of atrial fibrillation and as an add-on to intravenous amiodarone for its pharmacological cardioversion: a meta-analysis.

INTRODUCTION: Recent evidence from relatively small randomized controlled trials would seem to support a useful role of ranolazine for the prevention and treatment of atrial fibrillation (AF). The present study is aimed at providing information about the possible beneficial anti-arrhythmic properties of ranolazine. In particular, the meta-analysis carried out in this study focuses on the application of ranolazine to prophylaxis and treatment of atrial fibrillation. EVIDENCE ACQUISITION: Both methods randomized controlled trials (RCTs) and non-randomized observational studies concerning the effects of ranolazine on AF were included in the meta-analysis. In each of the considered studies, a comparison was made between a group of patients taking ranolazine and a second group treated instead with another antiarrhythmic therapy, or assigned to placebo. Efficacy outcomes were the risk of new-onset AF, the probability of conversion to sinus rhythm of patients with recent occurrence (≤48 h) of AF and the time to conversion to sinus rhythm. Safety endpoints were death, adverse events, QTc prolongation and hypotension. EVIDENCE SYNTHESIS: Ten studies (8 RCTs and 2 nonrandomized observational studies) were gathered on the whole. Ranolazine was effective in preventing the occurrence of AF when compared to controls (RR=0.60; 95% CI: 0.43-0.83; P=0.002). Subgroup analysis showed a more pronounced preventive effect of ranolazine against AF in the postoperative setting of coronary artery bypass grafting (CABG) surgery (RR=0.39; 95% CI: 0.18-0.83; P=0.02) when compared to non-postoperative AF (RR=0.76; 95% CI: 0.63-0.92; P=0.04). Ranolazine enhanced the chances of successful cardioversion when added to intravenous amiodarone compared to amiodarone alone (RR 1.18; 95% CI: 1.05-1.33; P=0.004) and significantly decreased the time to cardioversion (SMD= -10.35 h; 95% CI: -18.13 hours to -2.57 hours; P<0.001). Overall risks of death, adverse events, and QTc prolongation were shown to be similar in the comparison between patients treated with ranolazine and controls. CONCLUSIONS: Ranolazine given orally at appropriate doses showed the property to significantly quicken the conversion of AF to sinus rhythm when combined with the IV amiodarone, compared to IV amiodarone alone. Furthermore, in patients in sinus rhythm, ranolazine proved to reduce the frequency of new onset AF as well as of its recurrences, especially in patients undergone CABG surgery, known to be at high risk of developing postoperative AF. In addition, ranolazine use seems to be safe and associated with relatively few adverse events.

Phosphodiesterase-5 Inhibitors Improve Clinical Outcomes, Exercise Capacity and Pulmonary Hemodynamics in Patients With Heart Failure With Reduced Left Ventricular Ejection Fraction: A Meta-Analysis.

BACKGROUND: Several studies have compared the use of phosphodiesterase-5 (PDE5) inhibitors sildenafil or udenafil with the placebo in patients suffering from pulmonary hypertension (PH) due to left chronic heart failure (CHF), corresponding to group 2 (PH due to left heart disease) of the PH classification (according to 2015 ESC/ERS guidelines for the diagnosis and treatment of PH). The results of the use of PDE5 inhibitors in the PH due to left heart disease were inconsistent and heterogeneous. Therefore, we carried out a meta-analysis to assess the effect of PDE5 inhibitors in this clinical setting, i.e., patients with left CHF. METHODS: A systematic search was conducted using the PubMed and Embase electronic archives. Studies had to be prospective randomized controlled trials (RCTs). In each of the RCTs admitted to meta-analysis, a comparison was made between a group of CHF patients taking a PDE5 inhibitor and a second group assigned a placebo. Studies were incorporated in the meta-analysis provided that they had sufficient information about two or more of the following clinical, ergospirometric or hemodynamic outcomes: the composite of all-cause death and hospitalization, adverse events, peak VO2, 6-min walking distance (6MWD), left ventricular ejection fraction (LVEF), E/e' ratio, mean pulmonary arterial pressure (mPAP), pulmonary arterial systolic pressure (PASP), and pulmonary vascular resistance (PVR). RESULTS: Fourteen studies enrolling a total of 928 patients were incorporated in the meta-analysis. Among them,13 were RCTs and one was a subgroup analysis. Among patients with CHF with reduced left ventricular ejection fraction (HFREF, n = 555), a significant benefit was conferred by PDE5 inhibitors against the risk of the composite endpoint of death and hospitalizations (odds ratio (OR): 0.28; 95% confidence interval (CI): 0.10 - 0.74; P = 0.03). Furthermore, among HFREF patients, PDE5 inhibitors were associated with a significant improvement in peak VO2 (difference in means (MD): 3.76 mL/min/kg; 95% CI: 3.27 - 4.25) as well as in 6MWD (MD: 22.7 m; 95% CI: 8.19 - 37.21) and LVEF (MD: 4.30%; 95% CI: 2.18% to 6.42%). For patients with HFREF, PDE5 inhibitors caused a non-significant reduction in mPAP, while PASP was significantly reduced (MD: -11.52 mm Hg; 95% CI: -15.56 to -7.49; P < 0.001). By contrast, in the RCTs of patients with CHF with preserved left ventricular ejection fraction (HFpEF, n = 373), no benefit ensued from PDE5 inhibitor use regarding all of the investigated clinical, ergospirometric or hemodynamic endpoints. CONCLUSIONS: PDE5 inhibitors improved clinical outcomes, exercise capacity and pulmonary hemodynamics in patients with HFREF, but not in HFpEF. However, considering the relatively small size of the HFpEF subset enrolled so far in the RCTs that explored the PDE5 inhibitor effects, further research in this field is undoubtedly warranted.

Does Accidental Overcorrection of Symptomatic Hyponatremia in Chronic Heart Failure Require Specific Therapeutic Adjustments for Preventing Central Pontine Myelinolysis?

This review aims at summarizing essential aspects of epidemiology and pathophysiology of hyponatremia in chronic heart failure (CHF), to set the ground for a practical as well as evidence-based approach to treatment. As a guide through the discussion of the available evidence, a clinical case of hyponatremia associated with CHF is presented. For this case, the severe neurological signs at presentation justified an emergency treatment with hypertonic saline plus furosemide, as indicated. Subsequently, as the neurological emergency began to subside, the reversion of the trend toward hyponatremia overcorrection was realized by continuous infusion of hypotonic solutions, and administration of desmopressin, so as to prevent the very feared risk of an osmotic demyelination syndrome. This very disabling complication of the hyponatremia correction is then briefly outlined. Moreover, the possible advantages related to systematic correction of the hyponatremia that occurs in the course of CHF are mentioned. Additionally, the case of tolvaptan, a vasopressin receptor antagonist, is concisely presented in order to underline the different views that have led to different norms in Europe with respect to the USA or Japan as regards the use of this drug as a therapeutic resource against the hyponatremia.

Estimating Right Atrial Pressure Using Ultrasounds: An Old Issue Revisited With New Methods.

Knowledge of the right atrial pressure (RAP) values is critical to ascertain the existence of a state of hemodynamic congestion, irrespective of the possible presence of signs and symptoms of clinical congestion and cardiac overload that can be lacking in some conditions of concealed or clinically misleading cardiac decompensation. In addition, a more reliable estimate of RAP would make it possible to determine more accurately also the systolic pulmonary arterial pressure with the only echocardiographic methods. The authors briefly illustrate some of the criteria that have been implemented to obtain a non-invasive RAP estimate, some of which have been approved by current guidelines and others are still awaiting official endorsement from the Scientific Societies of Cardiology. There is a representation of the sometimes opposing views of researchers who have studied the problem, and the prospects for development of new diagnostic criteria are outlined, in particular those derived from the matched use of two- and three-dimensional echocardiographic parameters.

B-type natriuretic peptide-guided versus symptom-guided therapy in outpatients with chronic heart failure: a systematic review with meta-analysis.

PURPOSE: It has been asserted that serial measurements of natriuretic peptides, specifically B-type natriuretic peptide (BNP) or the amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), may serve as an objective practical guide to better tailor the drug treatment for patients with chronic heart failure (CHF), and especially to detect the cases of subclinical congestion that would require an increase in drug dosing. However, considerable uncertainty remains about the alleged useful role of natriuretic peptide-guided therapy in this context. Therefore, we decided to execute a meta-analysis of published randomized controlled trials (RCTs) to test the hypothesis that an improvement of clinical outcomes in outpatients with CHF may be achieved by adjustment of pharmacologic dosing performed according to natriuretic peptide determinations. METHODS: The relevant studies were collected through a search across the PubMed database (January 1996 to September 2012). For our meta-analysis, parallel-group RCTs were eligible for inclusion if they met the following criteria: they enrolled patients with CHF, they randomized patients to a strategy of titrating drug therapy based on the level of a circulating natriuretic peptide (BNP or NT-proBNP) compared to a parallel control group treated according to the clinical conventional criteria, and they reported all-cause mortality. In addition, it was established that each RCT to be incorporated in the evaluation should have included more than 60 participants and its follow-up should have been longer than 90 days. The primary endpoint of the meta-analysis was all-cause mortality and hospitalization related to heart failure (combined endpoint). RESULTS: In the six pooled RCTs subjected to final meta-analysis (total of included patients = 1775), natriuretic peptide-guided therapy for outpatients with CHF was shown to be associated with a decreased risk of death and heart failure hospitalizations during follow-up (odds ratio - random effect model: 0.64; 95% confidence interval: 0.43-0.95; P = 0.026). CONCLUSION: This meta-analysis supports the hypothesis that natriuretic peptide-guided therapy is superior to symptom-guided therapy for improving clinical outcomes in CHF outpatients. However, some large RCTs failed to document significant clinical improvement in terms of mortality and morbidity using a natriuretic peptide-guided strategy; thus, any attempt to clarify this still unresolved issue by means of further basic and clinical research is recommended in the future.

Statin use for nonrheumatic calcific aortic valve stenosis: a review with meta-analysis.

AIMS: To synthesize by meta-analysis the findings of recent experimental studies focusing on possible therapeutic effectiveness of statins for nonrheumatic calcific aortic stenosis. METHODS: Observational studies and randomized controlled trials (RCTs) were selected from the Pubmed database to evaluate the hemodynamic progression of aortic stenosis in statin-treated patients compared with controls (i.e. patients with aortic stenosis taking placebo or no treatment). The endpoints were the annualized changes in one or more of the following ultrasonographic measurements: peak aortic valve jet velocity, peak aortic valve pressure gradient, mean aortic valve pressure gradient aortic valve area (AVA). For estimating the overall effect of statin therapy on each of the above-mentioned continuous variables across the considered studies, we used the weighted mean difference (WMD) as effect size measure. In addition, we calculated the odds of aortic valve replacement surgery and cardiovascular death in both statin-treated patients and controls for subsequently estimating the appropriate odds ratios. RESULTS: Nine studies were selected. A lower annualized increase in peak aortic valve jet velocity was found in statin-treated patients compared with controls (overall WMD: -0.09 m/s per year, 95% CI -0.16, -0.01 P = 0.018). Similarly, a smaller annualized increase in peak aortic valve pressure gradient was found in the statin group (overall WMD: -2.04 mmHg/year 95% CI: -3.56, -0.52, P = 0.0085). However, the overall effects in statin-treated patients on both annualized increases in mean aortic valve pressure gradient and decreases in AVA were not significantly different from those found in controls. Moreover, there was no significant difference in cardiovascular outcomes in the statin groups compared with placebo groups in each of the three analyzed RCTs and overall. CONCLUSION: Significant benefit of statin therapy in retarding hemodynamic deterioration was identified by favorable effects concerning annualized changes in peak aortic valve jet velocity and peak aortic valve pressure gradient; on the contrary, in statin-treated patients with aortic stenosis, no significant improvement was found for annualized changes in mean aortic valve pressure gradient and AVA and clinical outcomes.

Ultrasound evaluation of the inferior vena cava collapsibility index in congestive heart failure patients treated with intravenous diuretics: new insights about its relationship with renal function: an observational study.

OBJECTIVE: In chronic heart failure (CHF), collapsibility index of the inferior vena cava (IVCCI) is used for noninvasive ultrasonographic appraisal of central venous pressure, but it also may be related both to estimated glomerular filtration rate (eGFR) and renal outcome. METHODS: On the basis of retrospective observational cohort study, we analyzed 49 patients with right or biventricular CHF in III NYHA class, who had undergone intravenous intensive treatment with furosemide. Aggravated renal dysfunction (ARD) was defined by serum creatinine (Cr) increase of ≥0.3 mg/dL from baseline. IVCCI was categorized in three layers (IVCCI ≤15%, IVCCI 16-40% and IVCCI >40%). The predictors of ARD were searched for as well as any relation between basal IVCCI and both eGFR at admission and occurrence of ARD. RESULTS: Overall, 15 cases and 34 controls were compared. Multivariate predictors of ARD were a lower basal eGFR (HR: 0.82 CI: 0.72-0.94 p=0.0045) and intravenous furosemide daily mean dose >80 mg (HR: 48.62 CI: 1.62-3841.5 p=0.0430). A very significant positive correlation was found between IVCCI at admission ≤ 15% and basal eGFR (r=0.96 p<0.0001), while a negative correlation with eGFR was detected in the IVCCI highest (>40%) range (r=-0.696 p=0.0013). Furthermore, the category with basal IVCCI >40% showed a higher rate of ARD compared to that with basal IVCCI 16-40% (p<0.05). CONCLUSION: On the basis of the demonstrated u-shaped relationship between IVCCI and eGFR both the stratum with the highest (>40%) and the one with the lowest (≤15%) basal IVCCI may be associated with increased risk of ARD.

Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica / ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

FUNDAMENTO: O efeito renoprotetor dos inibidores da ECA vem sendo questionado no caso de diminuição do volume circulante efetivo, como na insuficiência cardíaca crônica direita ou biventricular. Objetivo: Detectar os preditores clínicos de agravamento renal na população de pacientes com ICC, caracterizado por dois tipos de regime de dosagem de inibidores da ECA. MÉTODOS: De acordo com um desenho de coorte retrospectiva, seguimos dois grupos de pacientes com ICC - tanto direita quanto biventricular -, todos na classe III da NYHA, tratados com inibidores da ECA (enalapril ou lisinopril), e com fração de ejeção do ventrículo esquerdo (FEVE) < 50 por cento, por meio de distinção em sua dosagem de inibidor da ECA: média-baixa (< 10 mg por dia) ou dosagem "alta" (> 10 mg por dia) de enalapril ou lisinopril. A disfunção renal agravada (ARD) foi definida pelo aumento de Cr > 30 por cento com relação ao segmento basal. O modelo de risco proporcional de Cox foi utilizado para identificar os preditores da ARD entre as seguintes variáveis: os inibidores da ECA com "alta" dosagem, idade, FEVE basal, histórico de repetidas terapias intensivas com diuréticos de alça por via intravenosa (diurético intravenoso), diabete, Cr basal, histórico de hipertensão, pressão arterial sistólica < 100 mmHg. RESULTADOS: Cinquenta e sete pacientes foram recrutados, dos quais 15 foram tratados com inibidor da ECA com dosagem "alta". Durante um seguimento médio de 718 dias, a ARD ocorreu em 17 pacientes (29,8 por cento). Apenas o inibidor da ECA com "alta" dosagem (RR: 12,4681 IC: 2,1614 - 71,9239 p = 0,0050) e Cr basal (RR:1,2344 IC: 1,0414 - 1,4632 p = 0,0157) foi demonstrado ser preditor da ARD. Além disso, demonstrou-se que o inibidor da ECA com dosagens "altas" não previu ARD em ICC sem diurético intravenoso e ICC com diabete. CONCLUSÃO: Na ICC de classe III da NYHA, o inibidor da ECA com "altas" dosagens e um maior Cr basal foi preditor da ARD. A nefrotoxicidade relacionada com inibidores da ECA em "altas" dosagens foi aumentada com o diurético intravenoso, ao passo que, em pacientes com ICC com diabete, aquela não foi detectada.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50 percent, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30 percent from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8 percent) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

The relation between carotid atherosclerotic plaques and ischemic stroke is critically conditioned by the role of arterial hypertension as an effect modifier.

BACKGROUND: Hypertension is a recognized risk factor for ischemic stroke (IS) along with diabetes, smoking, and hypercholesterolemia. Any uncertainty remains about other putative risk factors, ultrasound-derived, such as carotid soft plaques. METHODS: A case-control study was carried out concerning cases of IS or transient ischemic attack (TIA) found in an outpatient population from February 2000 to March 2008. For every patient with documented IS or TIA, 1 to 2 controls without previous cerebrovascular event were recruited. The variables analyzed were: hypertension, defined as mild hypertension (140-160 mm Hg) or moderate-to-severe hypertension (>160 mm Hg); age, divided into 3 classes: 60 to 70, 70 to 80, and 80 to 90 years; diabetes and carotid plaques, categorized as "soft" or "hard" plaques, and as plaques achieving mild (<50%) or moderate (50%-70%) luminal narrowing. RESULTS: Fourty-six cases and 60 controls were analyzed. In univariate analysis, moderate-to-severe hypertension, age between 80 and 90 years, carotid soft plaques and 50% to 70% stenoses predicted ischemic cerebral events. In multivariable analysis, only moderate-to-severe hypertension (odds ratio [OR]: 15.536; 95% confidence interval [CI]: 4.142-58.271; P = 0.0000) and oldest age class (OR: 15.862; 95% CI: 3.836-65.592; P = 0.0001) proved to predict IS or TIA. Soft plaques were found to predict risk of IS (OR: 13.50; 95% CI: 2.9788-61.1821) in hypertensive, but not in patients whose hypertension had been controlled by therapy (OR: 0.2308; 95% CI: 0.0270-1.9720) (qualitative interaction). CONCLUSIONS: Moderate-to-severe hypertension and very old age predicted IS and TIA, whereas carotid soft plaques did not, in the presence of normotensive blood pressure.

Restrictive left ventricular filling pattern and increase in antero-posterior left atrial diameter: two reliable predictors of clinical deterioration in chronic heart failure II NYHA class patients.

OBJECTIVE: To identify the Doppler echocardiographic criteria able to predict clinical deterioration of mild-to- moderate chronic heart failure (CHF) as well as, whenever possible, to evaluate the features of chronological relation of cavitary remodelling in left chambers during follow-up (FU). METHODS: A retrospective, case-controlled study, including a number of CHF II NYHA class patients, was carried out, to evaluate, by means of univariate and multivariable logistic regression analyses, the role as predictor of CHF worsening of some Doppler echocardiographic parameters, listed as follows: left ventricular mass index, analyzed both as continuous and as dichotomous (>130 g/m2) variable; left ventricular end-systolic volume (LVESV) >57 ml; left ventricular ejection fraction (LVEF), divided into 2 classes: a) LVEF>45%, i.e. normal or mildly impaired LVEF, and 2) reduced (45%-30%) LVEF; restrictive left ventricular filling pattern (RFP); antero-posterior left atrial diameter (LADi) >50 mm; ratio of early mitral inflow to early myocardial velocity>8. RESULTS: Of 173 patients enrolled, 60 patients (15 cases of transition to III NYHA class and 45 controls) were included in retrospective analysis. At univariate analysis, RFP and LADi>50 mm were shown to be associated with worsening of CHF. At multivariate analysis, the role of prognostic indicator of poor outcome was maintained by RFP (OR=17.0, 95%CI: 2.5-116.5) as well as by LADi>50 mm (OR=7.95, 95%CI: 1.27.0-49.6). On the other hand, in the subset of CHF with LVEF >45%, increased LADi was not associated with occurrence of increase in LVESV or left ventricular progressive dilation during the subsequent follow-up. CONCLUSIONS: In mild-to-moderate CHF, RFP and LADi>50 mm are predictors of adverse outcome, independently of the presence or severity of left ventricular systolic dysfunction.

Myocardial systolic activation delay in patients with left bundle branch block and either normal or impaired left ventricular function.

AIM OF THE STUDY: to evaluate determinants of myocardial activation delay of both left (LV) and right (RV) ventricle in patients with left bundle branch block (LBBB) and either normal or impaired LV ejection fraction (EF). METHODS: From an initial cohort of patients with LBBB, 42 patients with dilated cardiomyopathy (group A) and 33 with normal global LV systolic function (group B), all comparable in age and sex, underwent standard Doppler echo, pulsed Doppler myocardial imaging (DMI), and coronary angiography. Using DMI, the following regional parameters were evaluated in five different basal myocardial segments (LV anterior, inferior, septal, lateral walls-RV lateral wall): systolic (Sm), early- and late-diastolic (Em and Am) peak velocities. As index of myocardial systolic activation was calculated: precontraction time (PCTm) (from the beginning of Q-wave of ECG to the onset of Sm). Intraventricular systolic dyssynchrony was analyzed by difference of PCTm in different LV myocardial segments. Interventricular activation delay was calculated by the difference of PCTm between the most delayed LV segment and RV lateral wall. RESULTS: Patients of group A showed increased heart rate (HR), QRS duration and LV end-diastolic diameter, and reduced LV EF. By DMI, patients of group A showed reduced myocardial peak velocities and a significant intraventricular delay in activation of LV lateral wall, with increased regional PCTm (P < 0.001). In addition, patients with dilated cardiomyopathy showed a more pronounced interventricular dyssynchrony, even after adjustment for HR and QRS duration. By receiver operating characteristic (ROC) curve analysis, a cut-off value of 55 msec of interventricular delay showed 86% sensitivity and 92% specificity in identifying patients with impaired EF. In the overall population, by use of stepwise forward multivariate linear regression analyses, LV end-diastolic diameter (beta coefficient = 0.52; P < 0.001) and LV EF (beta coefficient =-0.58; P < 0.0001) were the only independent determinants of interventricular activation delay. CONCLUSIONS: Pulsed DMI is an effective noninvasive technique for assessing the severity of regional delay in activation of LV walls in patients with LBBB. The impairment of interventricular systolic sychronicity is strongly related to LV dilatation and to the degree of global systolic dysfunction. Therefore, patients with dilated cardiomyopathy suitable for cardiac resynchronization therapy may be better selected.