Prevalence and Predictors of Early Heart Failure With Preserved Ejection Fraction in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) have an increased risk of diastolic dysfunction and heart failure. The purpose of this study was to identify independent predictors of early (ie, only exercise-induced) heart failure with preserved ejection fraction (HFpEF) and to describe the prevalence of early HFpEF among patients with paroxysmal AF. METHODS AND RESULTS: One hundred patients with paroxysmal AF and preserved left ventricular ejection fraction (LVEF) underwent catheterization for left atrial pressure (LAP) measurements at rest and at the peak of arm exercise (LAP-exe). Based on resting and exercise LAP values, the patients were divided into 3 groups. Sixty-one patients had no evidence of HFpEF (LAP at rest ≤15 mm Hg, LAP-exe <25 mm Hg). Twenty-five subjects had early HFpEF (LAP at rest ≤15 mm Hg, LAP-exe ≥25 mm Hg, prevalence 25%). Fourteen patients already had HFpEF at rest (LAP at rest >15 mm Hg). Multivariate exact logistic regression analysis identified age ≥58 years, LAP at rest ≥11 mm Hg, and peak systolic mitral annular velocity ≤9.3 cm/s to be independent predictors of early HFpEF. CONCLUSIONS: In patients with paroxysmal AF and preserved LVEF, there appears to be a clinically significant prevalence of early HFpEF.

The unique value of cardiovascular magnetic resonance in patients with suspected acute coronary syndrome and culprit-free coronary angiograms.

BACKGROUND: Patients with chest pain, elevated troponin, and unobstructed coronary disease present a clinical dilemma. The purpose of this study was to investigate the incremental diagnostic value of cardiovascular magnetic resonance (CMR) in a cohort of patients with suspected acute coronary syndrome (ACS) and unobstructed coronary arteries. RESULTS: Data files of patients meeting the inclusion criteria in two cardiology centres were searched and analysed. The inclusion criteria included: 1) thoracic pain suspected with ACS; 2) a significant increase in the high-sensitive Troponin T value; 3) ECG changes; 4) coronary arteries without any significant stenosis; 5) a CMR examination included in the diagnostic process; 6) an uncertain diagnosis before the CMR exam; and 7) the absence of known CMR and contrast media contraindications. Special attention was paid to the benefits of CMR in determining the final diagnosis. In total, 136 patients who underwent coronary angiography for chest pain were analysed. The most frequent underlying causes were myocarditis (38%) and perimyocarditis (18%), followed by angiographically unrecognised acute myocardial infarction (18%) and Takotsubo cardiomyopathy (15%). The final diagnosis remained unclear in 6% of the patients. The contribution of CMR in determining the final diagnosis determination was crucial in 57% of the patients. In another 35% of the patients, CMR confirmed the suspicion and, only 8% of the CMR examinations did not help at all and had no influence on diagnosis or treatment. CONCLUSION: CMR provided a powerful incremental diagnostic value in the cohort of patients with suspected ACS and unobstructed coronary arteries. CMR is highly recommended to be incorporated as an inalienable part of the diagnostic algorithms in these patients.

Improvement in the prediction of exercise-induced elevation of left ventricular filling pressure in patients with normal left ventricular ejection fraction.

BACKGROUND: Noninvasive diagnosis of exercise-induced elevation of left ventricular filling pressure is difficult and remains unsatisfactory. The aim of this study was to assess the accuracy of the ratio of early diastolic transmitral (E) to mitral annular (e') velocity and to determine new parameters or parameter combinations with the ability to predict exercise-induced left atrial pressure (LAP) elevation. METHODS AND RESULTS: Eighty patients with paroxysmal atrial fibrillation (AF) referred for catheter AF ablation underwent simultaneous exercise echocardiography and direct invasive LAP measurements, as well as a resting and postexercise biomarker analysis. Exercise E/e' ≥8.85 predicted exercise LAP ≥20 mm Hg with 61.5% sensitivity and 88.9% specificity (area under the curve [AUC], 0.76). Of all of the individual parameters tested, the best prediction was achieved with exercise E/s' (s'=peak systolic mitral annular velocity) ≥8.75 (sensitivity, 88.5%; specificity, 64.8%; positive predictive value, 54.8%; negative predictive value, 92.1%; AUC, 0.84). However, the combination of exercise E/A (A = late diastolic transmitral flow velocity) ≥1.22 + exercise E/e' ≥8.85 + exercise s'≤11.05 cm/s provided the most precise prediction of exercise LAP elevation (sensitivity, 84.6%; specificity, 79.6%; positive predictive value, 66.7%; negative predictive value, 91.5%; AUC, 0.90). CONCLUSIONS: Exercise E/e', when used as a sole parameter, was not sufficiently reliable to predict exercise-induced elevation of LAP. The application of a multivariate-adjusted combination of parameters appeared to be the preferable approach for the noninvasive prediction of exercise LAP elevation.

[What is new in heart failure with preserved ejection fraction within last five years?]. / Co je nového v srdecním selhání se zachovalou ejekcní frakcí levé komory za posledních pet let?

Heart failure with preserved ejection fraction of left ventricle (heart failure with normal ejection fraction, HFPEF, HFNEF) is frequent disease with serious consequences. Incidence of HFPEF in population is still growing. The exact pathophysiological mechanism of HFPEF remain unclear .Recent evidence suggests a relationship between inflammation associated with obesity or Diabetes mellitus and progression of HFPEF. Consistently, it has been reported that serum concentration of some pro-inflammatory markers such as adiponectin is positively related to HFPEF. By HFPEF is attended diastolic dysfunction. Diastolic dysfunction is linked to many other cardiac and non-cardiac diseases. Despite the great effort and new therapeutic approaches the prognosis of HFPEF does not improve. The gold standard in HFPEF diagnosis remains heart catheterization. Electrocardiography, chest X-ray, blood examination including diagnostic markers of heart failure and mainly echocardiography with Doppler imaging are used diagnose the underlying disease leading to heart failure.

The prognostic effect of different types of cardiac rehabilitation in patients with coronary artery disease.

AIM: The purpose of this study was to access and compare the prognostic effects of different types of cardiac rehabilitation (CR) in patients with chronic coronary artery disease. METHODS: One hundred fifty-two patients were retrospectively divided into 4 groups according to their adherence to physical activity recommendations. Patients in groups 1 and 2 participated in the guided 3-month exercise programme. Patients in group 1 then continued with individual exercise training, while patients in the group 2 stopped exercising after finishing the guide exercise programme. Patients in group 3 participated only in individual exercise training throughout the whole follow-up period, and patients in group 4 declined all exercise recommendations and did not exercise. The prognostic outcome of different types of cardiac rehabilitation was compared among the groups. In addition, patients who participated in individual exercise training according to recommendations (cohort IT+) were compared with patients who declined these activities (cohort IT-). RESULTS: During a median follow-up of 94 months, 33 deaths occurred: 17 cardiovascular and 16 non-cardiac deaths. A Kaplan-Meier survival analysis demonstrated significantly better survival rates for patients who followed a long-term aerobic exercise training (IT+) than for those who did not participate or who had only a short-term exercise programme (IT-) (P = 0.009). CONCLUSION: In our study, long-term exercise training had a higher impact on patient survival than short-term guided CR.

Noninvasive prediction of the exercise-induced elevation in left ventricular filling pressure in post-heart transplant patients with normal left ventricular ejection fraction.

OBJECTIVES: At present, there are conflicting data on the ability of echocardiographic parameters to predict the exercise-induced elevation of left ventricular (LV) filling pressure. The purpose of the present study was to validate the ratio of early diastolic transmitral (E) to mitral annular velocity (e') obtained at peak exercise in its capacity to determine the exercise-induced elevation of pulmonary capillary wedge pressure (PCWP) and to reveal new noninvasive parameters with such capacity. METHODS: Sixty-one patients who had undergone heart transplantation with normal LV ejection fraction underwent simultaneous exercise echocardiography and right heart catheterization. RESULTS: In 50 patients with a normal PCWP at rest, exercise E/e' ≥8.5 predicted exercise PCWP ≥25 mmHg with a sensitivity of 64.3% and a specificity of 84.2% (area under the curve [AUC]=0.74). A comparable or slightly better prediction was achieved by exercise E/peak systolic mitral annular velocity (s') ≥11.0 (sensitivity 79.3%; specificity 57.9%; AUC=0.75) and exercise E/LV systolic longitudinal strain rate ≤-105 cm (sensitivity 78.9%; specificity 78.6%; AUC=0.87). Combined, exercise E/s' and exercise E/e' resulted in a trend toward a slightly more precise prediction (sensitivity 53.6%; specificity 89.5%; AUC=0.78) than did either variable alone. CONCLUSIONS: Exercise E/e', used as a sole parameter, is not sufficiently precise to predict the exercise-induced elevation of PCWP. Exercise E/s', E/LV systolic longitudinal strain rate or combinations of these parameters may represent further promising possibilities for predicting exercise PCWP elevation.

The role of exercise echocardiography in the diagnostics of heart failure with normal left ventricular ejection fraction.

AIMS: Few data are available on the exercise-induced abnormalities of myocardial function in patients with exertional dyspnoea and normal left ventricular ejection fraction (LV EF). The main aims of this study were to determine the prevalence of isolated exercise-induced heart failure with normal ejection fraction (HFNEF) and to assess whether disturbances in LV or right ventricular longitudinal systolic function are associated with the diagnosis of HFNEF. METHODS AND RESULTS: Eighty-four patients with exertional dyspnoea and normal LV EF and 14 healthy controls underwent spirometry, NT-proBNP plasma analysis, and exercise echocardiography. Doppler LV inflow and tissue mitral and tricuspid annular velocities were analysed at rest and immediately after the termination of exercise. Of the 30 patients with the evidence of HFNEF, 6 (20%) patients had only isolated exercise-induced HFNEF. When compared with the remaining patients, those with HFNEF had a significantly lower resting and exercise peak mitral annular systolic velocity (Sa) and the mitral annular velocity during atrial contraction, lower exercise peak mitral annular velocity at early diastole, and lower exercise peak systolic velocity of tricuspid annular motion. The multivariate logistic regression analysis including both parameters standardly defining HFNEF and the new Doppler variables potentially associated with the diagnosis of HFNEF revealed that NT-proBNP, LV mass index, left atrial volume index, and Sa significantly and independently predict the diagnosis of HFNEF. CONCLUSION: A significant proportion of patients require exercise to diagnose HFNEF. Sa appears to be a significant independent predictor of HFNEF, which may increase the diagnostic value of models utilizing the variables recommended by the European Society of Cardiology guidelines.

Estimation of left ventricular filling pressures by speckle tracking echocardiography in patients with idiopathic dilated cardiomyopathy.

AIMS: the ratio of early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (E(a)) is frequently used to predict an increase in left ventricular filling pressure (LVFP). However, this approach has several limitations. The aim of this study was to test whether additional information is gained by new echocardiographic indexes utilizing strain and strain rate (SR) derived from 2-dimensional speckle tracking echocardiography (2D-STE) for the estimation of LVFP. METHODS AND RESULTS: fifty-one patients with idiopathic dilated cardiomyopathy (IDC) underwent pulsed-wave tissue Doppler echocardiography and 2D-STE performed simultaneously with right heart catheterization. Receiver operating characteristic analysis showed that circumferential strain and the SR during late diastolic LV filling (0.956 and 0.951, both P = 0.001), E/circumferential SR at early diastolic LV filling (0.949, P = 0.001), and E/circumferential strain at the time of peak E-wave (0.948, P = 0.001) had greater area under the curve than the E/E(a) ratio (0.911, P = 0.001) for the prediction of pulmonary capillary wedge pressure > 12 mmHg. CONCLUSION: when compared with the E/E(a) ratio, several 2D-STE-derived parameters better estimated the increase in LVFP in patients with IDC.

Intracoronary delivery of bone marrow cells to the acutely infarcted myocardium. Optimization of the delivery technique.

OBJECTIVES: Intracoronary cell transplantation during catheter balloon inflations may be associated with adverse events. We studied the effectiveness of an alternative transplantation technique--intracoronary cell infusion. METHODS: Fourteen pigs, which had survived acute myocardial infarction, were randomized into 2 treatment groups and 2 controls. Three days after infarction, 12 pigs underwent allogeneic intracoronary mononuclear bone marrow cell transplantation using either the standard technique (short-term cell injections during repeat balloon inflations, technique A, n = 6) or continuous intracoronary cell infusion without balloon inflations (technique B, n = 6). Implanted cells were stained with fluorescent dye. After transplantation, the pigs were euthanized and myocardial samples were analyzed by fluorescent microscopy. RESULTS: The mean numbers of fluorescently labeled bone marrow cells in the infarction border zone, in the infarction mid-area and in the center of myocardial infarction were 84, 72 and 55 using technique A, and 29, 57 and 46 using technique B, respectively. The mean cell retention in the infarction border zone of 84 cells for technique A and 29 cells for technique B differed significantly (p = 0.034, two-tailed t test). CONCLUSION: The continuous intracoronary cell infusion technique is a less efficient cell delivery technique as compared with the standard technique using repeat intracoronary balloon inflations.

Association of coronary artery disease, erectile dysfunction, and endothelial nitric oxide synthase polymorphisms.

The purpose of this study was to determine the relationship between erectile dysfunction (ED), coronary artery disease (CAD), and T(-786)C and intron 4 a/b endothelial nitric oxide synthase (eNOS) polymorphisms in 419 patients with suspected or known CAD referred for coronary angiography. The patients had a high prevalence of risk factors for both CAD and ED: hypercholesterolemia (64%), hypertension (74%), diabetes mellitus (25%), obesity (30%), and smoking (63%). Three hundred and twenty-one patients had significant coronary atherosclerosis (luminal diameter narrowing of 50% or more of at least 1 coronary artery), 41 had insignificant coronary stenoses, and 57 patients were found to have coronary arteries without the evidence of atherosclerosis. The prevalence of ED in these groups was 79%, 76%, and 67% (P = NS), respectively. As compared to patients without ED, those with ED exhibited significantly higher probability of having significant coronary atherosclerosis (69% vs 79%, P = 0.04), higher number of significant coronary stenoses (median, 1 vs 2, P = 0.004), and a higher prevalence of a triple-vessel disease (12% vs 25%, P = 0.004). We did not find any relationship between T(-786)C and intron 4 a/b polymorphisms and the manifestation of coronary atherosclerosis or the presence of ED. In conclusion, in patients with numerous cardiovascular risk factors referred for coronary angiography, there was a high prevalence of ED in patients with both the presence and the absence of coronary atherosclerosis. The coincidence of CAD and ED identified patients at increased risk of severe forms of CAD.

Short-term effects of cardiac resynchronization therapy on sleep-disordered breathing in patients with systolic heart failure.

OBJECTIVES: We evaluated the short-term effect of cardiac resynchronization therapy (CRT) on sleep apnea in patients with systolic heart failure. BACKGROUND: Sleep-disordered breathing is common in patients with left ventricular systolic dysfunction. METHODS: Twelve patients (mean [+/-SE] age, 59.6+/-7.8 years; mean left ventricular ejection fraction, 28.0+/-2.8%) with an implanted atrial-synchronized biventricular pacemaker for the treatment of left ventricular systolic dysfunction were selected and studied. Each subject underwent polysomnography on 3 consecutive nights with CRT on the first night, CRT off the second night, and CRT on the third night. Echocardiography was performed prior to each polysomnogram. RESULTS: The central sleep event index (ie, the number of central sleep apneas [CSAs] and hypopneas per hour of sleep) score was lower with CRT compared to that without CRT (mean central sleep event index score with CRT on, 6.9+/-1.7 events per hour of sleep; mean central sleep event index score with CRT off, 14.3+/-2.9 events per hour of sleep; mean central sleep event index score with CRT on, 8.1+/-1.5 events per hour of sleep; p<0.001). Similarly, the cumulative duration of central sleep events (the number of minutes per hour of sleep during CRT) was one half that observed without CRT (CRT on, 2.8+/-0.7 min per hour of sleep; CRT OFF 6.2+/-1.2 min per hour of sleep; CRT ON 3.1+/-0.7 min per hour of sleep; p<0.001). There was a significant correlation between mitral regurgitant volume and central sleep event index on all three nights (r>or=0.77; p<0.01). CONCLUSIONS: CRT reduces CSA severity in the short term. This reduction correlated significantly with the CRT-mediated reduction of mitral regurgitation.

Individual differences in the effectiveness of intracoronary bone marrow cell transplantation assessed by gated sestamibi SPECT/FDG PET imaging.

BACKGROUND: The impact of different levels of tracer uptake on improvements of left-ventricular (LV) function was analyzed in patients treated by intracoronary bone marrow cell (BMC) transplantation. METHODS AND RESULTS: Thirty-one patients with irreversible damage after their first acute myocardial infarction (MI), as confirmed by sestamibi single-photon emission computed tomography (MIBI SPECT)/fluorodeoxyglucose positron emission tomography (FDG PET), underwent high-dose (1 x 10(8) cells) BMC transplantation, whereas 31 similar patients were randomly integrated into a control group. In 11 BMC-treated patients with very low sestamibi uptake at less than 30% of maximum in the infarcted area, the mean left-ventricular ejection fraction (LVEF) improved after 3 months of follow-up by 3% only, and mean end-diastolic/end-systolic volumes (EDV/ESV) enlarged by 10/1 mL (P = NS vs controls). In 20 BMC-treated patients with higher sestamibi uptake in the range of 31% to 50% of maximum, LVEF improved by 7%, and EDV/ESV decreased by 5/12 mL (P < .05 vs BMC-treated subgroup with low MIBI uptake and controls). No similar categorization was seen in the control group: in patients with higher sestamibi uptake or very low uptake, the LVEF increased by 2% and 3% only, and the EDV/ESV enlarged in both subgroups by 12/4 mL and 12/2 mL, respectively (P = NS). CONCLUSIONS: Our results suggest the capability of SPECT/PET imaging to select patients who will receive the maximum benefit from BMC therapy.

Cell therapy in patients with left ventricular dysfunction due to myocardial infarction.

OBJECTIVES: The purpose of this study was to determine the impact of autologous transplantation of mononuclear bone marrow cells on myocardial function in patients with left ventricular (LV) dysfunction due to an acute myocardial infarction. METHODS: The randomized study included 82 patients with a first acute myocardial infarction treated with a stent implantation. This presentation is a subanalysis of 47 patients with left ventricular dysfunction-EF (ejection fraction)

New echocardiographic parameters in the diagnosis of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a serious clinical disease. The pathophysiology of HFpEF is complex, and specific diagnostic criteria have evolved over time. Limited data are available on the quantification of diastolic function using two-dimensional real-time echocardiography, and a simple parameter has not yet been established. The aim of this work is to evaluate new echocardiographic parameters-the diastolic wall strain of the posterior wall (DWS PW) and the vortex formation time (VFT). Echocardiographic data from 111 subjects with exertional dyspnea and normal left ejection fraction (Group A) and 20 healthy volunteers (Group B) were retrospectively evaluated. In addition to the standard parameters used in the diagnosis of HFpEF, DWS PW and VFT were assessed in all patients. HFpEF was diagnosed in 38 patients with dyspnea (Group A1). The remaining 73 patients did not meet the established criteria for a positive diagnosis of HFpEF (Group A2). We discovered that both observed parameters were significantly lower in patients with HFpEF than in other groups. Multivariate analysis revealed that both DWS PW and VFT independently predicted the presence of HFpEF. DWS PW and VFT are simple parameters in the evaluation of diastolic function and may play a potential role as a part of an integrated approach to the assessment of HFpEF.

Ventricular dyssynchrony assessment using ultra-high frequency ECG technique.

PURPOSE: The aim of this proof-of-concept study is to introduce new high-dynamic ECG technique with potential to detect temporal-spatial distribution of ventricular electrical depolarization and to assess the level of ventricular dyssynchrony. METHODS: 5-kHz 12-lead ECG data was collected. The amplitude envelopes of the QRS were computed in an ultra-high frequency band of 500-1000 Hz and were averaged (UHFQRS). UHFQRS V lead maps were compiled, and numerical descriptor identifying ventricular dyssynchrony (UHFDYS) was detected. RESULTS: An electrical UHFQRS maps describe the ventricular dyssynchrony distribution in resolution of milliseconds and correlate with strain rate results obtained by speckle tracking echocardiography. The effect of biventricular stimulation is demonstrated by the UHFQRS morphology and by the UHFDYS descriptor in selected examples. CONCLUSIONS: UHFQRS offers a new and simple technique for assessing electrical activation patterns in ventricular dyssynchrony with a temporal-spatial resolution that cannot be obtained by processing standard surface ECG. The main clinical potential of UHFQRS lies in the identification of differences in electrical activation among CRT candidates and detection of improvements in electrical synchrony in patients with biventricular pacing.

Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: the effect of the dose of transplanted cells on myocardial function.

BACKGROUND: Despite the reports on successful treatment of acute myocardial infarction using autologous mononuclear bone marrow cell transplantation, many unresolved questions still remain. We studied the impact of the dose of transplanted cells on myocardial function and perfusion. METHODS: Sixty-six patients with a first acute myocardial infarction were randomized into 3 groups. Two groups were intracoronarily given mononuclear bone marrow cells in either higher (10(8) cells, higher cell dose [HD] group, n = 22) or lower (10(7) cells, lower cell dose [LD] group, n = 22) doses. Twenty-two patients without cell transplantation served as a control (C) group. RESULTS: At 3 months of follow-up, the baseline peak systolic velocities of longitudinal contraction of the infarcted wall of 5.2, 4.5, and 4.3 cm/s in C, LD, and HD groups increased by 0.0, 0.5 (P < .05 vs C group), and 0.9 cm/s (P < .05 vs LD group, P < .01 vs C group), respectively, as demonstrated by Doppler tissue imaging. Baseline left ventricular ejection fractions of 42%, 42%, and 41% in C, LD, and HD groups increased by 2%, 3%, and by 5% (P < .05 vs group C), respectively, as assessed by the gated technetium Tc 99m sestamibi single photon emission computed tomography. CONCLUSIONS: Mononuclear bone marrow cell transplantation improves regional myocardial function of the infarcted wall in a dose-dependent manner.

The role of quantitative Tc-99m-MIBI gated SPECT/F-18-FDG PET imaging in the monitoring of intracoronary bone marrow cell transplantation.

BACKGROUND: A lot of unresolved questions still exist concerning the exact mechanism of the beneficial effects of bone marrow cell (BMC) transplantation for myocardial regeneration. The aim of this communication is to report the cases of patients with and without post-transplantation left ventricular function improvement. MATERIAL AND METHODS: To this study we included consecutive patients with irreversible damage after a first acute ST-elevation myocardial infarction treated by coronary angioplasty with stent implantation. The irreversible damage was identified by dobutamine echocardiography and confirmed by rest gated Tc-99m-MIBI gated SPECT and in the majority of patients by F-18-FDG PET imaging as well. Using 4D-MSPECT software, we quantified MIBI/FDG uptake and gated SPECT left ventricular ejection fraction, end-diastolic/end-systolic volumes (LVEF, EDV/ESV) before BMC therapy and 3 months later. RESULTS: The results obtained in the initial group of patients in this study (27 patients in the BMC treated group, 16 patients in the control group) have been published previously [Eur J Nucl Med 2005; 32 (Suppl 1 ): S46]. Among the BMC group, we identified 13 responders to therapy with average LVEF improvement from 43.3% +/- 11% to 51.4% +/- 10.4% and EDV/ESV improvement from 145 ml/84 ml to 133 ml/67 ml. The remaining 14 patients were non-responders to therapy with no significant change in LVEF (39.1% +/- 8.1% versus 39.8% +/- 7.4%), the EDV/ESV increased from 166 ml/105 ml to 188 ml/116 ml. Responders to the cell therapy had prevailing MIBI uptake in the range of 31-50% of maximum in the infarction territory. On the other hand, non-responders to BMC therapy had prevailing MIBI uptake in the range of 0-30% of maximum. Two cases are presented in this report. CONCLUSIONS: Further studies with a larger cohort of patients would be helpful to evaluate our findings. We observed strong interindividual differences in the effectiveness of the cell therapy. Prevailing residual MIBI uptake in the range of 31-50% of maximum was in the subgroup of responders to the cell therapy.

Longitudinal, circumferential and radial systolic left ventricular function in patients with heart failure and preserved ejection fraction.

INTRODUCTION: Heart failure with preserved left ventricular ejection fraction (HFPEF) is an epidemiologically serious disease. Noninvasive diagnosis of HFPEF remains challenging. The current diagnosis is based on evidence of diastolic dysfunction, albeit systolic dysfunction is also present but not included in the diagnostic algorithm. The aim of this study was to analyze the longitudinal (long), circumferential (circ) and radial (rad) component of systolic left ventricular (LV) function in patients with exertional dyspnea of unexplained etiology and normal left ventricular ejection fraction (LVEF). METHODS: One hundred and twenty-two patients with exertional dyspnea of unexplained etiology and normal LVEF and 21 healthy controls, underwent echocardiography examination at rest and at the end of symptom-limited exercise. We analysed the longitudinal, circumferential and radial deformation of myocardium using two dimensional speckle tracking echocardiography in all subjects. RESULTS: Patients with exertional dyspnea and preserved LVEF were divided into group A1 (46 patients meeting the criteria for the diagnosis HFPEF) and group A2 (76 patients without HFPEF). Group A1 had significantly worse longitudinal and circumferential systolic LV function than group A2. Subjects in group A1 compared to group A2 showed significantly different strain rates during atrial contraction (SR A), circ and ratio of peak early trans-mitral flow velocity (E) and strain rate E wave (E / SR E) circ. Multivariate logistic regression analysis showed that the SR parameter A circ is an independent predictor of HFPEF (odds ratio 0.550, 95% confidence interval: 0.370 - 0.817, P value 0.003). CONCLUSION: Longitudinal and circumferential LV deformation was significantly more impaired in patients with HFPEF than in patients with exertional dyspnea without HFPEF. In patients with exertional dyspnea and normal LVEF, the value of SRA circ appears to be a significant and independent predictor of HFPEF. This parameter may, in the future complement the diagnostic algorithm for HFPEF.

Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina.

OBJECTIVES: The primary objective of the Monotherapy Assessment of Ranolazine In Stable Angina (MARISA) trial was to determine the dose-response relationship of ranolazine, a potentially new anti-anginal compound, on symptom-limited exercise duration. BACKGROUND: Fatty acids rise precipitously in response to stress, including acute myocardial ischemia. Ranolazine is believed to partially inhibit fatty acid oxidation, shift metabolism toward carbohydrate oxidation, and increase the efficiency of oxygen use. METHODS: Patients (n = 191) with angina-limited exercise discontinued anti-anginal medications and were randomized into a double-blind four-period crossover study of sustained-release ranolazine 500, 1,000, or 1,500 mg, or placebo, each administered twice daily for one week. Exercise testing was performed at the end of each treatment during both trough and peak ranolazine plasma concentrations. RESULTS: Exercise duration at trough increased with ranolazine 500, 1,000, and 1,500 mg twice daily by 94, 103, and 116 s, respectively, all greater (p < 0.005) than the 70-s increase on placebo. Dose-related increases in exercise duration at peak and in times to 1 mm ST-segment depression at trough and peak and to angina at trough and peak were also demonstrated (all p < 0.005). Ranolazine had negligible effects on heart rate and blood pressure. One year survival rate combining data from the MARISA trial and its open-label follow-on study was 96.3 +/- 1.7%. CONCLUSIONS: In chronic angina patients, ranolazine monotherapy was well tolerated and increased exercise performance throughout its dosing interval at all doses studied without clinically meaningful hemodynamic effects. One-year survival was not lower than expected in this high-risk patient population. This metabolic approach to treating myocardial ischemia may offer a new therapeutic option for chronic angina patients.

Right ventricular dysfunction in chronic heart failure patients.

AIM: To evaluate any differences in haemodynamic and echocardiographic parameters in patients with both left (LV) and right ventricular (RV) systolic dysfunction and in patients with isolated LV systolic dysfunction. STUDY GROUP: One hundred patients with RV systolic dysfunction defined as peak velocity of tricuspid annular motion in systole (Sa)<11.5 cm/s, and 55 patients without RV systolic dysfunction Sa>11.5 cm/s. All patients had LV systolic dysfunction, LV ejection fraction (EF) below 40%, NYHA II-IV. METHODS: LV diameters, volumes and EF were measured by echocardiography. Patients underwent tissue Doppler imaging (TDI) of tricuspid annular motion with measurement of peak systolic velocity (Sa), peak early (Ea) and peak late (Aa) diastolic velocities. Right heart catheterization was also performed. RESULTS: Patients with RV systolic dysfunction did not differ from those without RV systolic dysfunction in terms of LV function. Patients with RV systolic dysfunction had larger RV dimension 30.6+/-5.8 vs. 33.9+/-6.7 mm, p<0.002. The patients with RV systolic dysfunction had higher values on right heart catheterization: MPAP 29.6+/-12.1 vs. 24.9+/-11.4 mm Hg, p<0.02, PCWP 20.8+/-10.0 vs. 17.3+/-9.3 mm Hg, p<0.03, PVR 189.9+/-123.3 vs. 137.7+/-94.9 dyn s cm(-5), p<0.008, CVP 7.7+/-5.6 vs. 5.1+/-3.9 mm Hg, p<0.002. The patients with RV systolic dysfunction had more pronounced diastolic dysfunction measured by TDI: Ea 9.9+/-2.3 vs. 11.4+/-2.5 cm/s, p<0.0001 and Aa 13.1+/-4.0 vs. 16.5+/-4.7 cm/s, p<0.000007. CONCLUSION: Patients with heart failure and both left and right ventricular systolic dysfunction showed more serious findings on central haemodynamics as well as more pronounced right ventricular diastolic dysfunction than those with isolated left ventricular systolic dysfunction.