Correlation of Left Atrial Strain and Doppler Measurements with Invasive Measurement of Left Ventricular End-Diastolic Pressure in Patients Stratified for Different Values of Ejection Fraction.

BACKGROUND: This study aimed at exploring the correlation of left atrial longitudinal function by speckle tracking echocardiography (left atrial strain) and Doppler measurements (E/E' ratio) with direct measurements of left ventricular (LV) end-diastolic pressure (LVEDP) in patients stratified for different values of ejection fraction. METHODS: The study population was 80 stable patients with sinus rhythm undergoing cardiac catheterization. This population was selected in order to have four groups of 20 patients each with different LV ejection fraction (>55%, 45-54%, 30-44%, and <30%). LVEDP was obtained during cardiac catheterization; peak atrial longitudinal strain (PALS) and mean E/E' ratio were measured in all subjects. RESULTS: Similar correlations with LVEDP of global PALS and E/E' ratio were recorded in patients with preserved (r = -0.79 vs. r = 0.72, respectively; P < 0.0001 for both) or mildly reduced ejection fraction (r = -0.75 vs. r = 0.73, respectively; P < 0.0001 for both). A closer correlation of global PALS compared to E/E' ratio was evident in patients with moderate (r = -0.78 P < 0.0001; vs. r = 0.47 P = 0.01, respectively) and severe reduction (r = -0.74 P < 0.0001; vs. r = 0.19 ns, respectively) of LV ejection fraction. In multivariate analysis of all measurements, global PALS emerged as a determinant of the LVEDP, independent on other confounding factors and, with the cutoff value of 18.0% presented the best diagnostic accuracy to predict a LVDP above 12 mmHg (AUC 0.87). CONCLUSIONS: In patients with preserved or mildly reduced LV ejection fraction, global PALS and mean E/E' ratio presented good correlations with LVEDP. In patients with moderate or severe reduction of ejection fraction, E/E' ratio correlated poorly with invasively obtained LV filling pressures. Global PALS provided an overall better estimation of LV filling pressures.

Effects of ω-3 PUFAs supplementation on myocardial function and oxidative stress markers in typical Rett syndrome.

Rett syndrome (RTT) is a devastating neurodevelopmental disorder with a 300-fold increased risk rate for sudden cardiac death. A subclinical myocardial biventricular dysfunction has been recently reported in RTT by our group and found to be associated with an enhanced oxidative stress (OS) status. Here, we tested the effects of the naturally occurring antioxidants ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on echocardiographic parameters and systemic OS markers in a population of RTT patients with the typical clinical form. A total of 66 RTT girls were evaluated, half of whom being treated for 12 months with a dietary supplementation of ω-3 PUFAs at high dosage (docosahexaenoic acid ~71.9 ± 13.9 mg/kg b.w./day plus eicosapentaenoic acid ~115.5 ± 22.4 mg/kg b.w./day) versus the remaining half untreated population. Echocardiographic systolic longitudinal parameters of both ventricles, but not biventricular diastolic measures, improved following ω-3 PUFAs supplementation, with a parallel decrease in the OS markers levels. No significant changes in the examined echocardiographic parameters nor in the OS markers were detectable in the untreated RTT population. Our data indicate that ω-3 PUFAs are able to improve the biventricular myocardial systolic function in RTT and that this functional gain is partially mediated through a regulation of the redox balance.

Acute and long-term efficacy and safety of sildenafil for the treatment of chronic thromboembolic pulmonary hypertension in a heart transplant recipient.

We report on the successful treatment with sildenafil of a unique case of severe chronic thromboembolic pulmonary hypertension which developed as a late complication in a 71-year-old heart transplant recipient, with focus on the potential therapeutic challenges encountered in the management of such a peculiar association of clinical conditions.

The prognostic role of different renal function phenotypes in patients with acute heart failure.

OBJECTIVE: Worsening renal function (WRF) is common in patients treated for acute heart failure (AHF) and might be associated with a significant increase in blood nitrogen urea (BUN). Although many patients develop WRF during hospitalisation, its prognostic role is still unclear. Thus, we aimed to evaluate the prognostic relevance of WRF according to BUN changes during hospitalization. METHODS: We studied patients with AHF screened for Diur-HF Trial (NCT01441245). WRF was defined as an in-hospital rise in serum creatinine ≥0.3 mg/dl or estimated glomerular filtration rate (GFR) reduction ≥20%. BUN increase was defined as a rise in BUN ≥20% during admission. Effective decongestion was defined as complete resolution of two, or more, signs of HF, or absence of clinical signs of congestion at discharge. RESULTS: Of 247 patients enrolled, 59 (23%) patients experienced WRF, 107 (43%) had a BUN increase ≥20%, and 111 (45%) were effectively decongested during hospitalization. During 180 days of follow-up, 136 patients died or were re-hospitalised for AHF. An increase in BUN was an independent predictor of adverse outcome, regardless of WRF (HR = 2.19 [1.35-3.54], p = 0.002 and 1.71 [1.14-2.59], p = 0.010; with and without WRF, respectively) or congestion at discharge. WRF was not an independent predictor of outcome if BUN did not increase or when congestion was effectively relieved. CONCLUSIONS: an increase in BUN≥20% during hospitalization for AHF predicts a poor outcome independently from renal function deterioration and decongestion. WRF predicts adverse outcome only if BUN increases substantially or clinical congestion persists.

Takotsubo cardiomyopathy in a Caucasian Italian woman: case report.

BACKGROUND: Takotsubo cardiomyopathy is an acute cardiac syndrome characterized by transient LV regional wall motion abnormalities (with peculiar apical ballooning appearance), chest pain or dyspnea, ST-segment elevation and minor elevations of cardiac enzyme levels CASE PRESENTATION: A 68-year-old woman was admitted to the Emergency Department because of sudden onset chest pain occurred while transferring her daughter, who had earlier suffered a major seizure, to the hospital. The EKG showed sinus tachycardia with ST-segment elevation in leads V2-V3 and ST-segment depression in leads V5-V6, she was, thus, referred for emergency coronary angiography. A pre-procedural transthoracic echocardiogram revealed regional systolic dysfunction of the LV walls with hypokinesis of the mid-apical segments and hyperkinesis of the basal segments. Coronary angiography showed patent epicardial coronary arteries; LV angiography demonstrated the characteristic morphology of apical ballooning with hyperkinesis of the basal segments and hypokinesis of the mid-apical segments. The post-procedural course was uneventful; on day 5 after admission the echocardiogram revealed full recovery of apical and mid-ventricular regional wall-motion abnormalities. CONCLUSION: Takotsubo cardiomyopathy is a relatively rare, unique entity that has only recently been widely appreciated. Acute stress has been indicated as a common trigger for the transient LV apical ballooning syndrome, especially in postmenopausal women. The present report is a typical example of stress-induced takotsubo cardiomyopathy in a Caucasian Italian postmenopausal woman.

Left Atrial Strain Predicts Pro-Thrombotic State in Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) has a high prevalence in the population and it is responsible for up to the 25% of the strokes in elderly people. The aim of our study was to assess the correlations of left atrial (LA) functional parameter, global peak atrial longitudinal strain (PALS), derived from speckle tracking echocardiography (STE), with transesophageal echocardiography (TEE) findings in patients with persistent AF undergoing TEE before electrical cardioversion or ablation procedures. METHODS: 79 patients (58 males, 21 females) with persistent AF waiting for cardioversion were included in the study. The patients underwent conventional two-dimensional (2D) and 2D speckle tracking echocardiogram. PALS were measured in all subjects. Patients were divided into two groups according to the presence of reduced LA appendage (LAA) emptying velocity (<25 cm/s) and/or thrombus in the LAA at TEE examination. RESULTS: Patients with reduced LAA emptying velocity and/or thrombus at TEE examination showed a significantly higher LA volume and increased E/E' ratio. 4-chamber, 2-chamber and global PALS were significantly lower in patients with reduced LAA emptying velocity and/or thrombus (6.8 ± 2.0% vs. 27.5 ± 5.4%, P < 0.0001; 8.6 ± 3.5% vs. 29.4 ± 7.1%, P < 0.0001; 7.9 ± 3.2% vs. 28.5 ± 6.1%, P <0.0001, respectively). Among all variables analyzed, global PALS demonstrated the highest diagnostic accuracy (AUC of 0.92) and, with a cut-off value less than 8.1%, good sensitivity and specificity of 87% and 94%, respectively, to predict LAA thrombus and/or reduced LAA emptying velocity.

Effects of levosimendan on heart failure in normotensive patients: does loading dose matter?

BACKGROUND: Levosimendan is a calcium sensitizer and K(+)-ATP channel opener with inotropic and vasodilatatory effects irrespective of myocardial oxygen consumption, used for treatment of heart failure (HF). A loading dose is usually given by infusion for 12 h; however, profound lowering of blood pressure often disrupts or prolongs the infusion. The aim of this study was to assess clinical, biochemical and myocardial differences between different regimes of levosimendan therapy, with or without loading dose, and compared to standard therapy in heart failure. METHODS: Fifty-seven patients (mean age ± SD: 60.9 ± 9.3 years, 45 males) with HF, New York Heart Association (NYHA) III-IV, reduced left ventricular ejection fraction (LVEF) were included. Twenty patients (NB group) were given levosimendan without loading dose, 14 patients (B group) were given levosimendan with loading dose, and 23 patients (C group) were given standard therapy. Clinical, biochemical and echocardiographic characteristics at baseline and one week after treatment were evaluated. RESULTS: Groups were similar at baseline. After one week NHYA class (P < 0.001), NT pro-BNP (P < 0.001), LVEF (P = 0.045), E/A (P = 0.048) E/e' (P < 0.001), and PAPs (P < 0.001) decreased. DT (P = 0.011) and TAPSE (P = 0.035) increased in all groups. CONCLUSIONS: Levosimendan, as well as standard therapy, improves myocardial function and symptoms of HF, irrespective of the loading dose administration. Treatment options for patients with end-stage heart failure refractory to conventional medical therapy are limited. Inotropic drugs play an important role in heart failure (HF).

Neurohumoral improvement and torsional dynamics in patients with heart failure after treatment with levosimendan.

BACKGROUND: Levosimendan improves clinical and hemodynamic parameters exerting an anti-inflammatory and antiapoptotic effect in decompensated heart failure. The aim of this study was to evaluate the effects of levosimendan on LV torsion, plasma levels of NT-proBNP and on the balance between pro-inflammatory (TNF-α, IL-6) and anti-inflammatory cytokines (IL-10). METHODS: We enrolled 24 patients (age 62 ± 7 years) with acute HF, NYHA class IV and severe LV dysfunction. All patients underwent transthoracic echocardiography using two-dimensional speckle tracking analysis to detect LV twist angle (LVTA), at baseline and 1 week after treatment with levosimendan infusion. Biochemical parameters (pro-BNP, IL-6, IL-10, TNF-α) were determined by enzyme-linked immunosorbent (ELISA). RESULTS: After one week, we observed an improvement in LV function especially in LVTA (4.15 ± 2.54 vs 2.9 ± 2.1 p < 0.01), in LV ejection fraction (27.3 ± 8.04 vs 21.6 ± 6.8 p = 0.03) and also a significant reduction in BNP levels (1844 ± 560 vs 4713 ± 1050, p = 0.03). The multiple linear regression analysis showed a significant relation between a reduction of TNF α/IL-10 ratio (Δ > 20%) and BNP (Δ > 40%), LVEF (Δ > 10%) and LVTA (Δ > 20%) (O.R. 1.77, 95% C.I. 1.11-2.83; O.R. 1.49, 95% C.I. 1.08-2.67; O.R. 1.66, 95% C.I. 1.10-2.74, respectively, confirmed p, all < 0.01 by Hosmer-Lemeshov confirmation and the formal test for interaction). CONCLUSIONS: Levosimendan exerts a hemodynamic effect by improving EF and LV torsion in patients with acute HF in association with a positive effect on the balance between pro and anti-inflammatory cytokines.

Subclinical myocardial dysfunction in Rett syndrome.

AIMS: Rett syndrome (RTT) is a rare neurodevelopmental disorder frequently linked to methyl-CpG-binding protein 2 (MeCP2) gene mutations. RTT is associated with a 300-fold increased risk of sudden cardiac death. Rhythm abnormalities and cardiac dysautonomia do not to fully account for cardiac mortality. Conversely, heart function in RTT has not been explored to date. Recent data indicate a previously unrecognized role of MeCP2 in cardiomyocytes development. Besides, increased oxidative stress markers (OS) have been found in RTT. We hypothesized that (i) RTT patients present a subclinical biventricular dysfunction and (ii) the myocardial dysfunction correlate with OS. METHODS AND RESULTS: We evaluated typical (n = 72) and atypical (n = 20) RTT female and healthy controls (n = 92). Main outcome measurements were (i) echocardiographic biventricular systo-diastolic parameters; (ii) correlation between echocardiographic measures and OS levels, i.e. plasma and intra-erythrocyte non-protein-bound iron (NPBI) and plasma F2-Isoprostanes (F2-IsoPs). A significant reduction in longitudinal biventricular function (tricuspid annular plane systolic excursion, mitral annular plane systolic excursion, S' of lateral and septal mitral annulus, S' of tricuspidal annulus) was evidenced in RTT patients vs. controls. No significant changes in the LV ejection fraction were found. Peak-early filling parameters (E, E' of lateral mitral annulus, E' of tricuspidal annulus) and right ventricular systolic pressure were reduced. A-wave, E/A, and E/E' were normal. OS markers were increased, but only F2-IsoPs correlated to LV systolic dysfunction. CONCLUSION: These data indicate a previously unrecognized subclinical systo-diastolic biventricular myocardial dysfunction in typical and atypical RTT patients. A reduced preload is evidenced. The biventricular dysfunction is partially related to OS damage.

Profiling cardiac resynchronization therapy patients: responders, non-responders and those who cannot respond--the good, the bad and the ugly?

Cardiac resynchronization therapy (CRT) is an effective option for the management of heart failure (HF) patients with left ventricular systolic dysfunction and prolongation of the QRS interval. Unfortunately, a variable proportion of eligible patients fail to benefit from this treatment, the so-called "non-responders". Despite intensive investigations aimed at identifying reliable diagnostic tools, additional to standard criteria, for the selection of responders, partly due to the complexity and multi-factorial nature of the mechanism underlying response, no conclusive evidence is currently available about which of the many variables assessed may predict individual response and should be included in selection criteria. Accordingly, even if labeled as a non-responder, a patient should receive a CRT device being the certain risk of withholding the treatment more consistent than the potential risk of being a non-responder. However, a possible third profile of patients along with responders and non-responders is emerging consisting of a limited subset of individuals, mainly among those with HF of ischemic aetiology, who simply do not possess the anatomical requisite for conventional biventricular pacing to be effective. Such patients may be referred to as those who cannot respond to CRT and their identification is potentially feasible by integrating non-invasive imaging findings and of clinical relevance in the definition of the therapeutic strategy. In conclusion, this review will provide an analysis of gathered data about the selection of candidates to CRT beyond responders and non-responders with the perspective of the potential characterization of patients who cannot respond to CRT.

Influence of aetiology on long-term effects of resynchronization on cardiac structure and function in patients treated with ß-blockers.

OBJECTIVES: Cardiac resynchronization therapy (CRT) elicits more beneficial effects on left-ventricular (LV) structure and function, and long-term clinical outcomes in nonischemic heart failure patients. Rates of ß-blocker use in recent heart failure trials are higher than in CRT trials and this may influence the response to CRT. This study examined the long-term effects of CRT on LV structure and function in New York Heart Association class III-IV ß-blocker-treated patients. METHODS: One hundred and four (41 ischemic and 63 nonischemic) CRT patients, who were receiving ß-blockers before and throughout 12 months following device implantation, were retrospectively selected. Variations in echocardiographic parameters recorded before, and 6 and 12 months after CRT were analyzed. RESULTS: Selected patients were all stable on ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (97%) and diuretics (97%) before implantation. CRT was associated with significant improvements in LV morphological and systo-diastolic functional parameters at 6 months, with further improvements between 6 and 12 months seen in nonischemic patients only. Accordingly, rates of echocardiographic response to CRT were similar at 6 months but significantly higher in nonischemic patients after 1 year. The degree of reduction in LV diameters and volumes, and of increase in ejection fraction, was significantly larger in nonischemic patients at both 6 and 12 months. In addition, a significant reduction in LV mass and severity of mitral regurgitation was more evident in nonischemic patients both 6 and 12 months following CRT. CONCLUSIONS: Ischemic aetiology of heart failure is associated with less favorable long-term effects of CRT on LV structure and function despite the systematic use of ß-blockers.

Usefulness of left ventricular diastolic dysfunction assessed by pulsed tissue Doppler imaging as a predictor of atrial fibrillation recurrence after successful electrical cardioversion.

The impact of left ventricular (LV) diastolic dysfunction on risk of atrial fibrillation (AF) recurrence is still unknown. The aim of this study was to assess the role of LV diastolic dysfunction in predicting AF recurrence after successful electrical cardioversion in patients with nonvalvular AF. In 51 patients with a first episode of nonvalvular AF undergoing successful electrical cardioversion, tissue Doppler echocardiography was performed to measure peak early diastolic mitral annulus velocity (E(m)) and the ratio of mitral inflow to mitral annulus velocity at end-diastole (E/E(m)). Clinical end points were recurrent persistent AF at 2-week follow-up (early AF recurrence [ERAF]) and at 1-year follow-up (including ERAF and late AF recurrence). Seventeen patients showed evidence of ERAF, whereas late AF recurrence occurred in another 5 patients. In time-independent analysis E/E(m) (odds ratio [OR] 1.746, p = 0.0084) and indexed LV end-systolic volume (OR 1.083, p = 0.040) were independent predictors of ERAF. Based on a logistic model risk of ERAF was 25% for an E/E(m) of 5.6 but increased to 50% for an E/E(m) of 8.1 and to 75% for an E/E(m) of 10.5. In time-dependent analysis E/E(m) emerged as the only predictor of ERAF (OR 1.757, p = 0.0078). E/E(m) also independently predicted risk of recurrence at 1 year in time-independent (OR 1.757, p = 0.0078) and time-dependent (OR 1.319, p = 0.0003) analyses. In conclusion LV diastolic dysfunction independently predicts AF recurrence in patients with nonvalvular AF undergoing successful electrical cardioversion.

Effects of levosimendan without loading dose on systolic and diastolic function in patients with end-stage heart failure.

BACKGROUND: Levosimendan (L) is used in clinical practice for the treatment of severe heart failure (HF); it has inotropic and vasodilatory effects, without increasing myocardial oxygen consumption. In acute HF, levosimendan improves hemodynamic parameters; previous studies have demonstrated that it has favorable effects on left ventricular (LV) diastolic function. The aim of our study was to evaluate the effect of on LV long-axis function that represents the earlier marker of diastolic dysfunction. METHODS: We enrolled 41 patients (age 62 ± 12 years) admitted to our Department for acute HF, NYHA class IV and severe LV dysfunction. Twenty-six patients were treated with L (0.1 µg/kg/min ev for 24 h without loading dose) and 15 patients were treated with standard therapy (C). We evaluated clinical, blood exams and echocardiographic parameters at baseline and one week after L or C treatment. RESULTS: Baseline demographic, clinical and biochemical data were similar in both groups. After one week, the L group had shown a significant improvement in NYHA class and a reduction of pro-B-type natriuretic peptide (pro-BNP). In echocardiographic study, we observed an improvement in LV longitudinal function (p 〈 0.05) and LV ejection fraction (p 〈 0.05) with a reduction of E/E' (p 〈 0.05) in the L group. We divided the L group into ischemic and non- -ischemic patients and we demonstrated a significant increase in systolic function in the former. No differences were found between subgroups in diastolic function. CONCLUSIONS: L therapy, without loading dose, improves NYHA class and ventricular function in patients with acute HF; we believe that these prolonged hemodynamic effects are due to active metabolities of L.

Massive mitral regurgitation secondary to acute ischemic papillary muscle rupture: the role of echocardiography.

Papillary muscle rupture is an infrequent but often fatal mechanical complication of acute myocardial infarction (AMI). We report the case of an AMI complicated by the development of an abrupt cardiogenic shock due to the rupture of the head of the postero-medial papillary muscle with echocardiographic demonstration of severe mitral regurgitation due to flail posterior mitral valve leaflet. After initial stabilization with medical therapy and diagnostic coronary angiography, the patient was referred for urgent cardiac surgery and successfully underwent mitral valve replacement with implantation of a bioprosthesis. This case confirms the importance of transthoracic echocardiography in diagnosing mechanical acute complications during an AMI and in the decision making of patients with sudden onset of hemodynamic compromise. Transthoracic echocardiography should be immediately carried out in all patients in whom a mechanical complication during an AMI is suspected.

Cardiogenic shock complicating myocardial infarction in a doped athlete.

Abuse of doping agents may pose a higher risk for heart disease including acute myocardial infarction. We report the case of a 50-year-old body-builder Caucasian man with a long-standing abuse of nandrolone and erythropoietin that developed a ventricular septal defect following acute myocardial infarction. This mechanical complication led to cardiogenic shock ultimately treated with the implantation of a circulatory support by means of extracorporeal membrane oxygenation. The patient subsequently underwent orthotopic heart transplantation. The association of intense isometric exercise, abuse of erythropoietin and nandrolone is likely to have predisposed to coronary thrombus formation and acute myocardial infarction, as the patient presented no traditional cardiovascular risk factors.

[An unusual cause of syncope in hypertrophic cardiomyopathy]. / Una rara causa di sincope nella cardiomiopatia ipertrofica.

Syncope and pre-syncope represent common symptoms in patients with hypertrophic cardiomyopathy. The clinical scenario of recurrent and frequent syncopal episodes is one of the most challenging in the management of patients with hypertrophic cardiomyopathy. Syncope in hypertrophic cardiomyopathy patients usually recognizes two underlying mechanisms: arrhythmias or primary hemodynamic mechanism. The concomitant presence of myocardial ischemia is one of the potential triggers in the context of syncope due to hemodynamic mechanism. Myocardial ischemia is not generally related to epicardial coronary artery atherosclerotic disease but rather to the presence of partially obliterated intramural coronary arteries or narrowed vessels. We report the rare case of a patient with hypertrophic cardiomyopathy presenting with recurrent syncopal episodes due to myocardial ischemia secondary to severe stenosis of the left anterior descending coronary artery.

Unusual evolutionary electrocardiogram pattern in a white patient with apical hypertrophic cardiomyopathy.

We report the case of a 85-year-old white woman diagnosed with apical hypertrophic cardiomyopathy, in whom we observed an unusual progression of initial T waves inversion to a nearly normal electrocardiogram (EKG) to giant negative T waves and back to a nearly normal EKG.