Genotype-Phenotype Insights of Inherited Cardiomyopathies-A Review.

Background: Cardiomyopathies (CMs) represent a heterogeneous group of primary myocardial diseases characterized by structural and functional abnormalities. They represent one of the leading causes of cardiac transplantations and cardiac death in young individuals. Clinically they vary from asymptomatic to symptomatic heart failure, with a high risk of sudden cardiac death due to malignant arrhythmias. With the increasing availability of genetic testing, a significant number of affected people are found to have an underlying genetic etiology. However, the awareness of the benefits of incorporating genetic test results into the care of these patients is relatively low. Aim: The focus of this review is to summarize the current basis of genetic CMs, including the most encountered genes associated with the main types of cardiomyopathies: hypertrophic, dilated, restrictive arrhythmogenic, and non-compaction. Materials and Methods: For this narrative review, we performed a search of multiple electronic databases, to select and evaluate relevant manuscripts. Results: Advances in genetic diagnosis led to better diagnosis precision and prognosis prediction, especially with regard to the risk of developing arrhythmias in certain subtypes of cardiomyopathies. Conclusions: Implementing the genomic information to benefit future patient care, better risk stratification and management, promises a better future for genotype-based treatment.

Monoamine Oxidase (MAO) Is Expressed at the Level of Mitral Valve with Severe Regurgitation in Hypertrophic Obstructive Cardiomyopathy: A Case Report.

Hypertrophic obstructive cardiomyopathy (HOCM) is one of the most common hereditary heart diseases. The severely hypertrophied interventricular septum combined with the systolic anterior movement (SAM) of the mitral valve (MV) frequently cause a significant pressure gradient in the left ventricular outflow tract associated with varying degrees of mitral regurgitation (MR). We present the case of a 64-year-old female patient who was diagnosed with HOCM two years ago and was admitted to the Institute of Cardiovascular Disease with exertion dyspnea and fatigue. Transthoracic echocardiography revealed concentric, asymmetrical left ventricular hypertrophy, an elongated anterior mitral leaflet (AML) and a significant SAM causing severe regurgitation, with indication for valvular replacement Monoamine oxidase (MAO), a mitochondrial enzyme, with 2 isoforms, MAO-A and B, has emerged as an important source of reactive oxygen species (ROS) in the cardiovascular system, but literature data on its expression in valvular tissue is scarce. Therefore, we assessed MAO-A and B gene (qPCR) and protein (immune fluorescence) expression as well as ROS production (spectrophotometry and confocal microscopy) and in the explanted MV harvested during replacement surgery. MAO expression and ROS production (assessed by both methods) were further augmented following ex vivo incubation with angiotensin II, an effect that was reversed in the presence of either MAO-A (clorgyline) or B (selegiline) inhibitor, respectively. In conclusion, MAO isoforms are expressed at the level of severely impaired mitral valve in the setting of HOCM and can be induced in conditions that mimic the activation of renin-angiotensin-aldosterone system. The observation that the enzyme can be modulated by MAO inhibitors warrants further investigation in a patient cohort.

Risk stratification in patients with heart failure: the value of considering both global longitudinal left ventricular strain and mechanical dispersion.

In previous studies, mechanical dispersion (MD) predicted ventricular arrhythmias independently of left ventricular ejection fraction (LVEF). Moreover, the combination of MD and global longitudinal strain (GLS) increased the prediction of arrhythmic events. We investigated the prognostic value of a new 2-dimensional strain index, GLS/MD, in patients with heart failure (HF). We analyzed 340 consecutive HF outpatients in sinus rhythm. Echocardiography was performed at 1.6 ± 0.4 months after hospital discharge. The end point included sudden cardiac death, ventricular fibrillation, and sustained ventricular tachycardia (SCD/VA). During the follow-up period (36 ± 9 months), SCD/VA occurred in 48 patients (14.1%). A multivariate Cox regression analysis, which included LVEF, early diastolic transmitral / mitral annular velocity ratio (E/E'), GLS, MD, and GLS/MD in the model, revealed that GLS/MD was the best independent predictor of SCD/VA (HR = 3.22, 95% confidence interval = 1.72-6.15, p = 0.03). Separate inclusion of LVEF, systolic mitral annular velocity, E/E', GLS, and MD together with GLS/MD showed that GLS/MD remained the best predictor of SCD/VA (each p < 0.05). The optimal GLS/MD cutoff value to predict SCA/VA was -0.20%/ms (80% sensitivity, 76% specificity). Irrespective of LVEF, free survival was significantly better in patients with GLS/MD ≤ -0.2%/ms (log-rank test, p < 0.001). In conclusion, GLS/MD may improve cardiovascular risk stratification in subjects with HF.

Importance of Multimodality Cardiac Imaging in the Diagnosis of Lipomatous Hypertrophy of the Interatrial Septum-A View beyond Standard Situations.

Lipomatous hypertrophy of the interatrial septum (LHIAS) represents a benign proliferation of lipoid cells at the level of the interatrial septum (IAS) inducing an important thickening of this structure. It respects the fossa ovalis (FO) region, having a typical "hourglass" echocardiographic appearance. There are certain cases though, with unusual appearances and/or with associated pathologies that may induce similar lesions in the heart, in which the differential diagnosis cannot be guaranteed using only the standard methods. The final diagnosis has important implications in these patients' treatment plan. In this paper, we present an unusual case of a female patient undergoing chemotherapy for lung carcinoma, suspected of right atrial thrombosis/metastasis. As the diagnosis was unclear after transthoracic echocardiography (TTE), inducing the suspicion of an IAS mass with atrial wall infiltration, bi- and tridimensional transesophageal echocardiography (TOE) was performed, revealing a severely and homogenously hypertrophied IAS respecting the FO, but lacking a clear visualization of the atrial wall. The diagnosis of LHIAS was established by cardiac magnetic resonance (CMR) that certified the adipose nature of the structure, excluding the need for invasive investigations and/or treatment options. Multimodality imaging is very important for the clinician in adopting the best management plan for each individual patient.

The Challenges of Cardiac Resynchronization Therapy in Patients with Dilated Cardiomyopathy and Persistent Left Superior Vena Cava: A Case Report and Concise Literature Review.

Heart failure with reduced ejection fraction (HFrEF) is a chronic and debilitating disease, which requires extensive diagnostic and treatment resources in order to achieve an acceptable quality of life for the patient. While optimal medical treatment remains at the core of the disease's management, interventional cardiology also plays a very important role. However, in very rare situations, interventionists might find cases especially challenging due to the presence of venous anomalies, such as persistent left superior vena cava (PLSVC), anomalies that may go undiscovered during the patient's lifetime until venous cannulation is necessary. While these types of malformations also pose challenges in regards to standard pacemaker implantation, cardiac resynchronization (CRT) devices pose several additional challenges due to the complexity of the device and the necessity of finding an optimal position for the coronary sinus (CS) lead. We present the case of a 55-year-old male patient with advanced heart failure due to dilated cardiomyopathy (DCM) and LBBB who was a candidate for CRT-D therapy, describing the investigations that led to the discovery of the PLSVC as well as the technique and results of the intervention, while comparing our case to similar cases found in recent literature.

Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis: use of propensity score and instrumental variable methods to adjust for treatment-selection bias.

BACKGROUND: The impact of early surgery on mortality in patients with native valve endocarditis (NVE) is unresolved. This study sought to evaluate valve surgery compared with medical therapy for NVE and to identify characteristics of patients who are most likely to benefit from early surgery. METHODS AND RESULTS: Using a prospective, multinational cohort of patients with definite NVE, the effect of early surgery on in-hospital mortality was assessed by propensity-based matching adjustment for survivor bias and by instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection, and congestive heart failure. Of the 1552 patients with NVE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared with medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] versus 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction [ARR] -5.9%, P<0.001). With a combined instrument, the instrumental-variable-adjusted ARR in mortality associated with early surgery was -11.2% (P<0.001). In subgroup analysis, surgery was found to confer a survival benefit compared with medical therapy among patients with a higher propensity for surgery (ARR -10.9% for quintiles 4 and 5, P=0.002) and those with paravalvular complications (ARR -17.3%, P<0.001), systemic embolization (ARR -12.9%, P=0.002), S aureus NVE (ARR -20.1%, P<0.001), and stroke (ARR -13%, P=0.02) but not those with valve perforation or congestive heart failure. CONCLUSIONS: Early surgery for NVE is associated with an in-hospital mortality benefit compared with medical therapy alone.

Additive value of torsion to global longitudinal left ventricular strain in patients with reduced ejection fraction.

BACKGROUND: Torsional and longitudinal deformations are essential components of left ventricular (LV) performance. A precise assessment of LV function must take into account both LV torsion (LVtor) and global longitudinal strain (LVE). We compared a new 2D-strain parameter, LVtor x LVE, with several other echocardiographic parameters, with respect to their strength of association with N-terminal pro-brain natriuretic peptide (NTproBNP) in patients with reduced LV ejection fraction (LVEF). METHODS: Echocardiography was performed simultaneously with NTproBNP determination in 78 consecutive patients with reduced LVEF (<50%) in sinus rhythm. Early diastolic transmitral velocity/early mitral annular diastolic velocity ratio (E/E') and systolic mitral annular velocity (S') were measured. LVtor was defined as the ratio between LV twist (LVtw) and LV end-diastolic longitudinal length. LVtw (net difference between rotation angles at base and apex) was obtained from parasternal apical and basal short-axis planes. LVE was obtained by averaging longitudinal peak systolic strain of all 17 LV-segments (from apical planes). RESULTS: Log-transformed NTproBNP correlated significantly with LVE (r = 0.57, P < 0.001), myocardial performance index (r = 0.56, P < 0.001), systolic pulmonary artery pressure (r = 0.47, P < 0.001), E/E' (r = 0.41, P < 0.001), LVtor (r = -0.37, P = 0.001), E-velocity deceleration time (r = -0.37, P = 0.003), S' (r = -0.36, P = 0.002), LVtw (r = -0.34, P = 0.003), LVEF (r = -0.34, P = 0.003), E/A (A = late diastolic transmitral velocity, r = 0.30, P = 0.01) and E (r = 0.28, P = 0.03). LVtor x LVepsilon had the strongest correlation with log-NTproBNP (r = 0.70, P < 0.001). LVtor x LVepsilon was a better predictor of NTproBNP > 900 pg/ml (sensitivity = 82%, specificity = 84%) than other investigated parameters (each P < 0.05). CONCLUSIONS: In patients with reduced LVEF, LVtor x LVE is a promising parameter that deserves research to establish its clinical meaning and prognostic value.

Q fever endocarditis in Romania: the first cases confirmed by direct sequencing.

Infective endocarditis (IE) is a serious, life-threatening disease with highly variable clinical signs, making its diagnostic a real challenge. A diagnosis is readily made if blood cultures are positive, but in 2.5 to 31% of all infective endocarditis cases, routine blood cultures are negative. In such situations, alternative diagnostic approaches are necessary. Coxiella burnetii and Bartonella spp. are the etiological agents of blood culture-negative endocarditis (BCNE) most frequently identified by serology. The purpose of this study is to investigate the usefulness of molecular assays, as complementary methods to the conventional serologic methods for the rapid confirmatory diagnostic of Q fever endocarditis in patients with BCNE. Currently, detection of C. burnetii by culture or an antiphase I IgG antibody titers >800 represents a major Duke criterion for defining IE, while a titers of >800 for IgG antibodies to either B. henselae or B. quintana is used for the diagnosis of endocarditis due to Bartonella spp. We used indirect immunofluorescence assays for the detection of IgG titers for C. burnetii, B. henselae and B. quintana in 57 serum samples from patients with clinical suspicion of IE. Thirty three samples originated from BCNE patients, whereas 24 were tested before obtaining the blood cultures results, which finally were positive. The results of serologic testing showed that nine out of 33 BCNE cases exhibited antiphase I C. burnetii IgG antibody titer >800, whereas none has IgG for B. henselae or B. quintana. Subsequently, we used nested-PCR assay for the amplification of C. burnetii DNA in the nine positive serum samples, and we obtained positive PCR results for all analyzed cases. Afterwards we used the DNA sequencing of amplicons for the repetitive element associated to htpAB gene to confirm the results of nested-PCR. The results of sequencing allowed us to confirm that C. burnetii is the causative microorganism responsible for BCNE. In conclusion, the nested PCR amplification followed by direct sequencing is a reliable and accurate method when applied to serum samples, and it may be used as an additional test to the serological methods for the confirmatory diagnosis of BCNE cases determined by C. burnetii.

Single-Pass VDD Pacing Lead for Cardiac Resynchronization Therapy: A Reliable Alternative.

(1) Background: Cardiac resynchronization therapy (CRT) systems can be simplified by excluding the atrial lead and using a Ventricular-Dual-Dual (VDD) pacing lead. Possible disadvantages might include atrial undersensing and Ventricular-Ventricular-Inhibition (VVI) pacing. Because literature data concerning these systems are scarce, we analyzed their benefits and technical safety. (2) Methods: this retrospective study compared 50 patients implanted with VDD-CRT systems (group A), mainly because of unfavorable venous anatomy concerning the complication rate, with 103 subjects with Dual-Dual-Dual (DDD)-CRT systems (group B) implanted during 2000-2016 and 49 (group C) during 2016-2020. To analyze the functional parameters of the devices, we selected subgroups of 27 patients (subgroup A) and 47 (subgroup B) patients with VDD-CRT in 2000-2016, and 36 subjects (subgroup C) with DDD-CRT implanted were selected in 2017-2020. (3) Results: There was a trend of a lower complication rate with VDD-CRT systems, especially concerning infections during 2000-2016 (p = 0.0048), but similar results were obtained after rigorous selection of patients and employment of an upgraded design of devices/leads. With a proper device programing, CRT pacing had similar results, atrial undersensing being minimal (p = 0.65). For VDD-systems, VVI pacing was recorded only 1.7 ± 2.24% of the time. (4) Conclusions: In patients with a less favorable venous anatomy, VDD-CRT systems may represent a safe alternative regarding complications rates and functional parameters.

Echocardiographic Parameters as Predictors for the Efficiency of Resynchronization Therapy in Patients with Dilated Cardiomyopathy and HFrEF.

Cardiac resynchronization therapy (CRT) represents an increasingly recommended solution to alleviate symptomatology and improve the quality of life in individuals with dilated cardiomyopathy (DCM) and heart failure (HF) with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy (OMT). However, this therapy does have the desired results all cases, in that sometimes low sensing and high voltage stimulation are needed to obtain some degree of resynchronization, even in the case of perfectly placed cardiac pacing leads. Our study aims to identify whether there is a relationship between several transthoracic echocardiographic (TTE) parameters characterizing left ventricular (LV) performance, especially strain results, and sensing and pacing parameters. Between 2020-2021, CRT was performed to treat persistent symptoms in 48 patients with a mean age of 64 (53.25-70) years, who were diagnosed with DCM and HFrEF, and who were still symptomatic despite OMT. We documented statistically significant correlations between global longitudinal strain, posterolateral strain, and ejection fraction and LV sensing (r = 0.65, 0.469, and 0.534, respectively, p < 0.001) and LV pacing parameters (r = -0.567, -0.555, and -0.363, respectively, p < 0.001). Modern imaging techniques, such as TTE with cardiac strain, are contributing to the evaluation of patients with HFrEF, increasing the chances of CRT success, and allowing physicians to anticipate and plan for case management.

E/(EaxSa) estimates left ventricular end-diastolic pressure in patients with severe mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: The early diastolic transmitral velocity/early mitral annular diastolic velocity ratio (E/Ea) reflects left ventricular (LV) filling pressure in a variety of cardiac diseases. The value of this parameter in patients with significant mitral regurgitation (MR) remains controversial. It has been hypothesized that, by combining the index of diastolic function (E/Ea) and a parameter that explores LV systolic performance (Sa, mitral annulus peak systolic velocity), a close prediction of the LV end-diastolic pressure (LVEDP) can be provided. Hence, the study aim was to assess the relationship between a new parameter, E/(EaxSa), and LVEDP in patients with severe MR. METHODS: A total of 55 consecutive patients with severe MR, in sinus rhythm, who had been referred for heart catheterization, was analyzed. Echocardiography was performed simultaneously with LVEDP measurements. Both, E/Ea and E/(EaxSa) were calculated, using the average of the velocities of the septal and lateral mitral annulus. RESULTS: A significant linear correlation was demonstrated between E/(EaxSa) and LVEDP (r = 0.81, p < 0.001); this was superior to E/Ea (r = 0.73, p < 0.001), Sa (r = -0.59, p = 0.004), pulmonary artery systolic pressure (r = 0.57, p = 0.007), E-wave (r = 0.45, p = 0.009), Ea (r = -0.31, p = 0.01), and left atrial volume (r = 0.28, p = 0.02). No significant relationships could be demonstrated between LVEDP and the LV ejection fraction. The area under the receiver-operating characteristic (ROC) curve for prediction of LVEDP > 15 mmHg was greatest for E/(EaxSa) (AUC = 0.87, p < 0.001), followed by the E/Ea ratio (AUC = 0.81, p < 0.001). A statistical comparison of the ROC curves indicated that E/(EaxSa) was more accurate than E/Ea (p = 0.02). The optimal E/(EaxSa) cut-off to predict a LVEDP > 15 mmHg was 1.95 (85% sensitivity, 83% specificity). CONCLUSION: E/(EaxSa) correlates strongly with LVEDP, and can serve as a simple and accurate echocardiographic index for the estimation of LVEDP in patients with severe MR.

Romanian Registry of Hypertrophic Cardiomyopathy - overview of general characteristics and therapeutic choices at a national level.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a disease with increased left ventricular (LV) wall thickness not solely explained by abnormal loading conditions, with great heterogeneity regarding clinical expression and prognosis. The aim of the present study was to collect data on HCM patients from different centres across the country, in order to assess the general characteristics and therapeutic choices in this population. METHODS: Between December 2014 and April 2017, 210 patients from 11 Romanian Cardiology centres were enrolled in the National Registry of HCM. All patients had to fulfil the diagnosis criteria for HCM according to the European Society of Cardiology guidelines. Clinical, electrocardiographic, imaging and therapeutic characteristics were included in a predesigned online file. RESULTS: Median age at enrolment was 55 ± 15 years with male predominance (60%). 43.6% of the patients had obstructive HCM, 50% non-obstructive HCM, while 6.4% had an apical pattern. Maximal wall thickness was 20.3 ± 4.8 mm (limits 15-37 mm) while LV ejection fraction was 60 ± 8%. Heart failure symptoms dominated the clinical picture, mainly NYHA functional class II (51.4%). Most frequent arrhythmias were atrial fibrillation (28.1%) and non-sustained ventricular tachycardia (19.9%). Mean sudden cardiac death risk score (SCD-RS) was 3.0 ± 2.3%, with 10.4% of the patients with high risk of SCD. However, only 5.7% received an ICD. Patients were mainly treated with beta-blockers (72.9%), diuretics (28.1%) and oral anticoagulants (28.6%). Invasive treatment of LVOT obstruction was performed in a small number of patients: 22 received myomectomy and 13 septal ablation. Cardiac magnetic resonance was reported in only 14 patients (6.6%). CONCLUSIONS: The Romanian registry of HCM illustrates patient characteristics at a national level as well as the gaps in management which need improvement - accessibility to high-end diagnostic tests and invasive methods of treatment.

Monoamine Oxidases as Potential Contributors to Oxidative Stress in Diabetes: Time for a Study in Patients Undergoing Heart Surgery.

Oxidative stress is a pathomechanism causally linked to the progression of chronic cardiovascular diseases and diabetes. Mitochondria have emerged as the most relevant source of reactive oxygen species, the major culprit being classically considered the respiratory chain at the inner mitochondrial membrane. In the past decade, several experimental studies unequivocally demonstrated the contribution of monoamine oxidases (MAOs) at the outer mitochondrial membrane to the maladaptative ventricular hypertrophy and endothelial dysfunction. This paper addresses the contribution of mitochondrial dysfunction to the pathogenesis of heart failure and diabetes together with the mounting evidence for an emerging role of MAO inhibition as putative cardioprotective strategy in both conditions.

The prognostic value of a new tissue Doppler parameter in patients with heart failure.

It has been shown a good accuracy to predict high left ventricular end-diastolic pressure for a value >1.6 of a new tissue Doppler index, E/(E' × S'), including the ratio between early diastolic transmitral and mitral annulus velocity (E/E'), and the systolic mitral annulus velocity (S'). Our aim was to evaluate the prognostic value of E/(E' × S') > 1.6 in patients with heart failure (HF). Echocardiography was performed in 345 consecutive hospitalized patients with HF, in sinus rhythm, at hospital discharge and after 1 month. Worsening of E/(E' × S') was defined as any increase of baseline value. The primary end point consisted of cardiac death or readmission due to HF worsening in long term follow-up. At discharge, 153 patients (44.3%) presented E/(E' × S') ≤ 1.6 (group I) while 192 patients (55.7%) presented E/(E' × S') > 1.6 (group II). During the follow-up period (35.1 ± 8.7 months) the first cardiac event was cardiac death in 11 patients (3.1%) and readmission for HF in 179 patients (51.9%). The composite end point was significantly higher in group II than in group I (163 events, 84.9 % vs. 27 events, 17.6%, p < 0.001). By multivariate Cox regression analysis, E/(E' × S') > 1.6 was the best independent predictor of cardiac events (hazard ratio = 4.46, 95% CI = 2.44-8.13, p = 0.001). Patients with E/(E' × S') > 1.6 at discharge and its worsening after 1 month have presented the worst prognosis (all p < 0.05). In patients with HF, E/(E' × S') > 1.6 at hospital discharge is a powerful predictor of clinical outcome particularly if it is associated with worsening.

A new tissue Doppler index to predict cardiac death in patients with heart failure.

BACKGROUND: It has been shown that a new tissue Doppler index, E/(E'×S'), including the ratio between early diastolic transmitral and mitral annular velocity (E/E'), and the systolic mitral annular velocity (S'), has a good accuracy to predict left ventricular filling pressure. OBJECTIVES: We investigated the value of E/(E'×S') to predict cardiac death in patients with heart failure. METHODS: Echocardiography was performed in 339 consecutive hospitalized patients with heart failure, in sinus rhythm, after appropriate medical treatment, at discharge and after one month. Worsening of E/(E'×S') was defined as any increase of baseline value. The end point was cardiac death. RESULTS: During the follow-up period (35.2 ± 8.8 months), cardiac death occurred in 51 patients (15%). The optimal cut-off value for the initial E/(E'×S') to predict cardiac death was 2.83 (76% sensitivity, 85% specificity). At discharge, 252 patients (74.3%) presented E/(E'×S') ≤ 2.83 (group I) and 87 (25.7%) presented E/(E'×S') > 2.83 (group II), respectively. Cardiac death was significantly higher in group II than in group I (38 deaths, 43.7% vs 13 deaths, 5.15%, p < 0.001). By multivariate Cox regression analysis, including variables that affected outcome in univariate analysis, E/(E'×S') at discharge was the best independent predictor of cardiac death (hazard ratio = 3.09, 95% confidence interval = 1.81-5.31, p = 0.001). Patients with E/(E'×S') > 2.83 at discharge and its worsening after one month presented the worst prognosis (all p < 0.05). CONCLUSIONS: In patients with heart failure, the E/(E'×S') ratio is a powerful predictor of cardiac death, particularly if it is associated with its worsening.

The value of left ventricular global longitudinal strain assessed by three-dimensional strain imaging in the early detection of anthracyclinemediated cardiotoxicity.

INTRODUCTION: Anthracyclines are important anticancer drugs, but their use is limited by acute and chronic cardiotoxicity. Current approaches to surveillance are often inadequate to detect myocardial disease. Strain imaging might detect earlier myocardial dysfunction. Speckle analysis of three-dimensional (3D) echocardiography improves information about left ventricular (LV) segmental and global deformation by avoiding the loss of speckles seen in monoplane bidimensional-strain analysis. We assessed whether early 3D-strain analysis could predict later anthracycline-induced cardiotoxicity. METHODS: Echocardiography, troponin T (TnT) and N-terminal pro-brain natriuretic peptide were used to evaluate 59 patients (age 51 ± 10 years) before, and at 12 and 36 weeks after anthracycline treatment. LV global longitudinal strain (3DGLS), global radial strain (3DGRS) and global circumferential strain (3DGCS) were determined using 3D-strain imaging before and after 12 weeks of chemotherapy. Percentage changes from baseline to 12 weeks after initiation of chemotherapy () were calculated for all parameters analysed. RESULTS: During the follow-up period, eight patients (13.5%) developed cardiotoxicity. At 12 weeks after the initiation of chemotherapy, isovolumic relaxation time, 3DGLS, 3DGCS and 3DGRS had deteriorated and troponin was elevated (all p<0.05), before any decrease in LV ejection fraction. Cumulative anthracycline dose at 12 weeks, LVEF, 3DGLS and TnT were predictors of the later development of cardiotoxicity on univariate logistic regression. By multiple logistic regression, 3DGLS emerged as the only independent predictor of later cardiotoxicity (Odds ratio 1.09, p=0.04). CONCLUSIONS: Anthracycline therapy induced early deterioration of 3DGLS, 3DGCS and 3DGRS. 3DGLS seems to be a good predictor of the future development of anthracycline-induced cardiotoxicity.

The value of a new speckle tracking index including left ventricular global longitudinal strain and torsion in patients with dilated cardiomyopathy.

INTRODUCTION: Torsional and longitudinal deformations are essential components of left ventricular (LV) performance. We believe that a precise assessment of LV function must take into account both LV torsion (LVtor) and global longitudinal strain (LVε). Therefore, we investigated with speckle tracking echocardiography the value of a new parameter, LVtor × LVε, for assessing LV function in dilated cardiomyopathy (DCM) and validated it against N-terminal pro-brain natriuretic peptide (NTproBNP). METHODS: Echocardiography was performed simultaneously with NTproBNP determination in 55 consecutive patients with DCM in sinus rhythm. The ratio of early diastolic transmitral velocity to early mitral annular diastolic velocity (E/E') was measured. LVtor was defined as the ratio between LV twist (LVtw) and LV enddiastolic longitudinal length. LVtw (net difference between rotation angles at base and apex) was obtained from parasternal apical and basal short-axis planes. LVε was obtained by averaging longitudinal peak systolic strain of all 17 LV-segments (from apical planes). RESULTS: Log-transformed NTproBNP correlated significantly with LVε (r=0.56, p<0.001), E/E' (r=0.52, p<0.001), LVtor (r=-0.41, p=0.003), LVtw (r=-0.38, p=0.004) and LV ejection fraction (r=-0.37, p=0.005). LVtor × LVε had the strongest correlation with log-NTproBNP (r=0.71, p<0.001). LVtor × LVε was a better predictor of NTproBNP levels >900 pg/ml (sensitivity 73%, specificity 82%) than LVε, E/E', LVtw, LVtor and LV ejection fraction (each p<0.05). CONCLUSIONS: This study demonstrates that in patients with DCM in sinus rhythm, the evaluation of LV function can be accurately accomplished by using a new speckle tracking index, LVtor × LVε.

A new tissue doppler index in predicting future atrial fibrillation in patients with heart failure.

BACKGROUND: Onset of atrial fibrillation (AF) in patients with heart failure (HF) is usually associated with a high occurrence of cardiovascular complications. E/(E'×S') ratio (E=early diastolic transmitral velocity, E'=early mitral annular diastolic velocity and S'=systolic mitral annulus velocity) has been shown to reflect left ventricular filling pressure. OBJECTIVE: We investigate whether E/(E'×S') could be a predictor of new-onset AF in patients with HF. METHODS: We analyzed 113 consecutive hospitalized patients with HF, in sinus rhythm, after appropriate medical treatment. Patients with histories of AF, inadequate echocardiographic images, congenital heart disease, paced rhythm, significant primary valvular disease, acute coronary syndrome, coronary revascularization during follow-up, severe pulmonary disease or renal failure were not included. E/(E'×S') was determined using the average of septal and lateral mitral annular velocities. The primary study end-point was the new-onset AF. RESULTS: During the follow-up period (35.7±11.2 months), 33 patients (29.2%) developed AF. Mean E/(E'×S') was 3.09±1.12 in these patients, while it was 1.72±1.34 in the other patients (p<0.001). The optimal E/(E'×S') cut-off to predict new-onset AF was 2.2 (88% sensitivity, 77% specificity). There were 64 patients (56.6%) with E/(E'×S')<2.2 and 49 (43.4%) with E/(E'×S')>2.2. New-onset AF was higher in patients with E/(E'×S')>2.2 than in patients with E/(E'×S')<2.2 [29 (59.1%) versus 4 (6.2%), p<0.001]. On multivariate Cox analysis including the variables that predicted AF on univariate analysis, E/(E'×S') was the only independent predictor of new-onset AF (hazard ratio=2.26, 95% confidence interval=1.25-4.09, p=0.007). CONCLUSION: In patients with HF, E/(E'×S') seems to be a good predictor of new-onset AF.

The influence of left bundle branch-block and cardiac dyssynchrony on 2D-strain parameters in patients with heart failure complicating ischemic cardiomyopathy.

UNLABELLED: Coronary artery disease is the underlying cause in approximately two-thirds of patients with heart failure. Torsional and longitudinal deformations are essential components of left ventricular (LV) performance. Electric conduction defects can reduce LV ejection fraction (LVEF) and decrease cardiac output. AIM: To investigate the influence of left bundle branch-block (LBBB) and cardiac dyssynchrony on 2D-strain parameters in patients with HF complicating ischemic cardiomyopathy. METHODS: We analyzed 106 consecutive patients with HF complicating ischemic cardiomyopathy, in sinusal rhythm. LV strain, LV twist and LV torsion were measured by echocardiographic 2D-strain imaging. LV dyssynchrony was assessed using validated tissue Doppler parameters. Patients were divided into three groups: HF with normal LVEF (group 1), HF with reduced LVEF without LBBB (group 2) and with LBBB (group 3). RESULTS: LVEF, LV strain, LV torsion and LV twist were significantly better in group 1 (each p < 0.01). In group 3, LV torsion and LV twist were significantly lower compared to group 2 (0.80 +/- 0.4 vs. 1.21 +/- 0.23 degrees/cm, p = 0.007, and 5.18 +/- 2.4 vs. 8.31 +/- 1.5 degrees, p = 0.004, respectively), but LV strain and LVEF were not different between group 3 and 2 (-4.91 +/- 2.3 vs. -6.28 +/- 1.8%, p = 0.056, and 30.6 +/- 8.8 vs. 34.4 = 8.3%, p = 0.11, respectively). Cardiac dyssynchrony induces a reduction of all 2D-strain analyzed parameters (each p < 0.05). CONCLUSION: In HF complicating ischemic cardiomyopathy, LBBB and cardiac dyssynchrony induce a reduction of LV strain, torsion and twist. In patients with reduced LVEF, LBBB induces predominantly a significant reduction ofLV torsion and LV twist, while LV strain was apparently not influenced.

Um Novo Indice de Doppler Tecidual para Prever Morte Cardiaca em Pacientes com Insuficiencia Cardiaca / A New Tissue Doppler Index to Predict Cardiac Death in Patients with Heart Failure

Fundamento: Foi demonstrado que um novo índice de Doppler Tecidual, E/(E'×S'), incluindo a proporção entre a velocidade diastólica precoce transmitral e a do anel mitral (E/E'), e a velocidade sistólica do anel mitral (S'), tem uma boa precisão como preditor da pressão de enchimento do ventrículo esquerdo. Objetivo: Investigar o valor de E/(E'×S') para prever a morte cardíaca em pacientes com insuficiência cardíaca. Métodos: Foi realizado sucessivamente o ecocardiograma em 339 pacientes hospitalizados com insuficiência cardíaca, em ritmo sinusal, após tratamento médico adequado, no momento e um mês depois da alta. O agravamento de E/(E'×S') foi definido como um aumento do valor padrão. O ponto final foi a morte cardíaca. Resultados: Durante o período de acompanhamento (35,2 ± 8,8 meses), ocorreu a morte cardíaca em 51 pacientes (15%). O melhor valor mínimo para E/(E'× S') inicial na previsão da morte cardíaca foi de 2,83 (76% de sensibilidade, 85% de especificidade). No momento da alta, 252 pacientes (74,3%) apresentaram E/(E'×S') ≤ 2,83 (grupo I), e 87 (25,7%) apresentaram E/(E'×S') > 2,83 (grupo II), respectivamente. A morte cardíaca foi significativamente maior no grupo II em relação ao grupo I (38 mortes, 43,7% contra 13 mortes, 5,15%, p < 0,001). Através da análise de regressão multivariada de Cox, incluindo as variáveis que afetaram os resultados na análise univariada, a relação E/(E'×S') no momento da alta mostrou-se o melhor preditor independente da morte cardíaca (taxa de risco = 3,09, 95% intervalo de confiança = 1,81-5,31, p = 0,001). Pacientes com E/(E'×S') > 2,83 no momento da alta e com um agravamento após um mês apresentaram o pior prognóstico (todos p < 0,05). ...

Background: It has been shown that a new tissue Doppler index, E/(E'×S'), including the ratio between early diastolic transmitral and mitral annular velocity (E/E'), and the systolic mitral annular velocity (S'), has a good accuracy to predict left ventricular filling pressure. Objectives: We investigated the value of E/(E'×S') to predict cardiac death in patients with heart failure. Methods: Echocardiography was performed in 339 consecutive hospitalized patients with heart failure, in sinus rhythm, after appropriate medical treatment, at discharge and after one month. Worsening of E/(E'×S') was defined as any increase of baseline value. The end point was cardiac death. Results: During the follow-up period (35.2 ± 8.8 months), cardiac death occurred in 51 patients (15%). The optimal cut-off value for the initial E/(E'×S') to predict cardiac death was 2.83 (76% sensitivity, 85% specificity). At discharge, 252 patients (74.3%) presented E/(E'×S') ≤ 2.83 (group I) and 87 (25.7%) presented E/(E'×S') > 2.83 (group II), respectively. Cardiac death was significantly higher in group II than in group I (38 deaths, 43.7% vs 13 deaths, 5.15%, p < 0.001). By multivariate Cox regression analysis, including variables that affected outcome in univariate analysis, E/(E'×S') at discharge was the best independent predictor of cardiac death (hazard ratio = 3.09, 95% confidence interval = 1.81-5.31, p = 0.001). Patients with E/(E'×S') > 2.83 at discharge and its worsening after one month presented the worst prognosis (all p < 0.05). Conclusions: In patients with heart failure, the E/(E'×S') ratio is a powerful predictor of cardiac death, particularly if it is associated with its worsening. .