Myocardial Work Brings New Insights into Left Ventricular Remodelling in Cardio-Oncology Patients.

Serial transthoracic echocardiographic (TTE) assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are the gold standard screening methods for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages to evaluate the impact of cardiotoxic treatments on heart function. We prospectively assessed breast cancer female patients undergoing cancer therapy through serial monitoring by 2D and 3D TTE. Patients were evaluated at T0, T1 and T2 (before, 4-6 and 12-14 months after starting therapy, respectively). Through PSL analysis, MW indices were calculated. A total of 122 patients, with a mean age of 54.7 years, who received treatment with anthracyclines (77.0%) and anti-HER2 (75.4%) were included. During a mean follow-up of 14.9 ± 9.3 months, LVEF and GLS were significantly diminished, and 29.5% developed CTRCD. All MW indices were significantly reduced at T1 compared with baseline and tended to return to baseline values at T2. Global work index and global work efficiency showed a more pronounced variation in patients with CTRCD. The presence of more than one cardiovascular risk factor, obesity and baseline left atrium volume were predictors of changes in MW parameters. In conclusion, breast cancer treatment was associated with LV systolic dysfunction as assessed by MW, with its peak at 4-6 months and a partial recovery afterwards. Assessment of myocardial deformation parameters allows a more detailed characterization of cardiac remodelling and could enhance patient screening and selection for cardioprotective therapeutics.

C-reactive protein reduction with sacubitril-valsartan treatment in heart failure patients.

OBJECTIVE: C-Reactive Protein (CRP) has emerged as an accessible measured product of inflammation. Whether systemic inflammation, a common feature of Heart Failure (HF), can be reduced by HF treatments in not well established. Sacubitril/Valsartan had prognosis benefit demonstrated in the PARADIGM-HF trial and was able to reduce proinflammatory cytokines in preclinical animal studies. However, no human studies evaluated if the benefits of this therapy are mediated by anti-inflammatory effects too. The aim of this study was to prospectively compare CRP values before and six months after Sacubitril-Valsartan therapy. METHODS: Prospective evaluation of chronic HF patients with left ventricular ejection fraction ≤ 40% despite optimized standard of care therapy, in which Sacubitril/Valsartan therapy was started and no additional HF treatment was expected to change. Clinical, laboratorial (including CRP values), electrocardiographic, transthoracic echocardiography and cardiopulmonary exercise test (CPET) data were gathered in the week before starting Sacubitril/Valsartan therapy and six months thereafter. RESULTS: There were 42 patients with a mean age of 59 ± 11 years, of which 35 completed the six months of follow-up, since 2 patients died and 5 discontinued treatment for adverse events. Patients with baseline CRP values above the median (> 2.5 mg/L) had a significantly higher percentage of New York Heart Association class ≥ III (65% vs. 33%, P=0.028) and a reduced exercise time in CPET (361 ± 297 vs. 575 ± 265 seconds, P=0.034). After 6 months of Sacubitril-Valsartan therapy, 24 (69%) patients had an improvement in CRP values with a significantly reduction as compared to baseline (median 2.5 mg/L (Interquartile range (IQR) 1.3-5.0) vs. 2.2 mg/L (IQR 0.9-4.0), P=0.014 in the Wilcoxon test). In the group of 17 (49%) patients with at least 25% improvement in CRP values with Sacubitril/Valsartan therapy, the benefit of several clinical, CPET and echocardiographic parameters were not significantly different from the benefit of patients with no improvement or an improvement inferior to 25% in CRP values. CONCLUSION: Sacubitril/Valsartan therapy was able to reduce CRP values in a chronic HF population. Whether this reduction was only a consequence of clinical improvement with Sacubitril/Valsartan or an anti-inflammatory effect is also present should be further evaluated.

Three-dimensional speckle-tracking echocardiography for the global and regional assessments of left ventricle myocardial deformation in breast cancer patients treated with anthracyclines.

BACKGROUND: Assessment of 2D/3D left ventricular ejection fraction (LVEF) and 2D global longitudinal strain (GLS) is the gold standard for diagnosing cancer therapeutics-related cardiac dysfunction (CTRCD). Although 3D speckle-tracking echocardiography (STE) has several advantages, it is not used in this setting. METHODS: 105 breast cancer patients who underwent serial echocardiographic assessment during anthracycline therapy were included. STE was used to estimate 2D GLS, 3D GLS, 3D global circumferential strain (GCS), 3D global radial strain (GRS), and 3D global area strain (GAS). CTRCD was defined as an absolute decrease in 2D/3D LVEF > 10% to a value < 54% or a relative decrease in 2D GLS > 15%. RESULTS: 24 patients developed CTRCD. There was a significant worsening of all 3D strain parameters during chemotherapy. 3D strain regional analysis showed impaired contractility in the anterior, inferior, and septal walls. Variations of 3D GRS and 3D GCS were associated with a higher incidence of CTRCD and the variation of 3D GRS was an independent predictor of CTRCD. Variations of 3D GCS and 3D GRS had a good discrimination for predicting CTRCD, with optimal cutoff values of - 34.2% for 3D GCS and - 34.4% for 3D GRS. These variations were observed 45 and 23 days before the diagnosis of CTRCD, respectively. CONCLUSION: Variations of 3D strain parameters were predictive of and preceded CTRCD, and thus have added value over currently recommended 2D/3D LVEF and 2D GLS. Routine application of this technique should be considered to offer targeted monitoring and timely initiation of cardioprotective treatment.

Cardiotoxicity in breast cancer treatment: What about left ventricular diastolic function and left atrial function?

AIMS: Cardiotoxicity is a possible complication of cancer treatment, particularly with anthracyclines and anti-HER2 drugs. Systolic dysfunction has already been described. Diastolic dysfunction and left atrial function are less studied. We sought to analyze the impact of cardiotoxic treatments on left ventricular diastolic function and left atrial (LA) function. METHODS AND RESULTS: Retrospective study of 100 patients (all women, with a mean age of 54 ± 12 years) with three exams in the span of 1 year during treatment for breast cancer. Patients with previous cancer treatment, coronary artery disease, significant valvular disease, and atrial arrhythmias were excluded. Diastolic dysfunction was classified according to international guidelines and left atrial strain was analyzed by two-dimensional speckle tracking. In our sample, 74% received anthracyclines, 83% anti-HER2, and 76% radiation treatment. In the follow-up, 20% developed new or worsening diastolic dysfunction. Age was the only independent predictor (OR 1.93, 95% CI 1.04-3.58, P = .037). In left atrial function, only the contractile function was significantly reduced in 20.8% of the patients and age was also the only independent predictor, but with a protective effect (OR 0.51, 95% CI 0.28-0.91, P = .023). CONCLUSIONS: During breast cancer treatment, 20% of the patients develop new or worsening diastolic dysfunction, being age the main determinant, suggesting higher impact of chemotherapy in older patients. Contractile left atrial function is also compromised but, in this case, age seems to be protective. Our results support a stricter surveillance in older patients together to eventually adjust chemotherapy regimens.

Antiarrhythmic Effect of Sacubitril-Valsartan: Cause or Consequence of Clinical Improvement?

Sacubitril/Valsartan (LCZ696) reduced sudden cardiac death in the PARADIGM-HF trial. However, the mechanism by which LCZ696 reduces ventricular arrhythmias remains unclear. The aim of this study was to compare electrocardiographic (ECG) parameters and mechanical dispersion index, assessed by left ventricular (LV) global longitudinal strain (GLS), before and after LCZ696 therapy. We prospectively evaluated chronic Heart Failure (HF) patients with LV ejection fraction ≤40%, despite optimal medical and device therapy, in which LCZ696 therapy was started, while no additional HF treatment was expected to change. ECG and transthoracic echocardiographic data were gathered in the week before starting LCZ696 and at six months of therapy. A semiautomated analysis of LV GLS was performed and mechanical dispersion index was defined as the standard deviation from 16 time intervals corresponding to each LV segment. Of the 42 patients, 35 completed the six month follow-up, since two patients died and five discontinued treatment for adverse events. QTc interval (451.9 vs. 426.0 ms, p < 0.001), QRS duration (125.1 vs. 120.8 ms, p = 0.033) and mechanical dispersion index (88.4 vs. 78.1 ms, p = 0.036) were significantly reduced at six months. LCZ696 therapy is associated with a reduction in QTc interval, QRS duration and mechanical dispersion index as assessed by LV GLS.

Infective endocarditis: Surgical management and prognostic predictors.

INTRODUCTION AND AIM: Infective endocarditis (IE) is associated with high morbidity and mortality. It is important to determine which factors increase the risk of poor outcome in order to enable early detection and aggressive treatment, including surgery. The aim of our study was to identify factors predicting complications and in-hospital mortality in patients with IE and to analyze conditions predisposing to surgery and its outcome. METHODS: We performed a retrospective study including patients with IE who underwent transesophageal echocardiography in a tertiary hospital center (2006-2014). RESULTS: A total of 233 patients were analyzed (69.1% male; mean age 63.4±15.2 years; mean follow-up 28.4±30.7 months). The complication rate was 56.6% and in-hospital mortality was 16.3%. Independent predictors of mortality were chronic obstructive pulmonary disease (OR 4.89; CI 1.36-17.63; p=0.015), clinical course complicated by cerebral embolism (OR 9.38; CI 3.26-26.96; p<0.001), and IE due to Staphylococcus spp. (OR 3.78; CI 1.32-10.85; p=0.014) and non-HACEK Gram-negative bacilli (OR 12.85; CI 2.61-63.23; p=0.002). Surgery was performed in 36.9%. This group had higher percentages of males, younger patients, aortic valve IE, large vegetations, perivalvular extension, severe valvular regurgitation and heart failure. In patients with surgical indication (n=133), those who underwent surgery had lower in-hospital mortality (15.5% vs. 32.6%, p=0.028) and better long-term survival (log-rank p=0.029). CONCLUSION: The results of this study may help to identify IE patients who are at increased risk of worse outcome, offering the opportunity to change the course of the disease and to improve prognosis with earlier and more aggressive intervention.

Modified continuity equation using left ventricular outflow tract three-dimensional imaging for aortic valve area estimation.

PURPOSE: Aortic valve area (AVA) is usually estimated by the continuity equation (CE) in which the left ventricular outflow tract (LVOT) area is calculated assuming a circular shape. This study aimed to compare measurements of LVOT area using standard 2D transthoracic echocardiography (2DTTE), 3D transesophageal echocardiography (3DTEE), and multidetector computed tomography (MDCT) and assess their relative impact on AVA estimated by the CE. METHODS AND RESULTS: We prospectively enrolled 60 patients with severe aortic stenosis (AS) referred for transcatheter aortic valve replacement (TAVR) who systematically underwent 2DTTE, 3DTEE, and MDCT. Mean LVOT areas obtained by 2DTTE (3.28±0.66 cm2 ) and 3DTEE (3.95±0.90 cm2 ) were significantly underestimated when compared to the mean MDCT LVOT area (4.31±0.99 cm2 ). LVOT was rather elliptical than round, with a mean eccentricity index of 1.47 (ratio of maximum to minimum LVOT diameters) assessed by MDCT. Mean TTE AVA estimated by the CE was 0.62±0.20 cm2 . Substitution of 2DTTE LVOT area by 3DTEE LVOT area in the CE resulted in AVA of 0.74±0.24 cm2 , while using MDCT LVOT area held an AVA of 0.80±0.24 cm2 . MDCT-derived AVA was similar to MDCT planimetric AVA and allowed 24% of patients to be reclassified from severe to moderate AS. CONCLUSIONS: 2DTTE and 3DTEE underestimate LVOT area when compared to MDCT with significant impact on AVA estimation. Assessment through MDCT fusion AVA may be of incremental value in patients with discrepant severity criteria for AS.

Predictors of response to cardiac resynchronization therapy: A prospective cohort study.

INTRODUCTION: Cardiac resynchronization therapy (CRT) has modified the prognosis of chronic heart failure (HF) with left ventricular systolic dysfunction. However, 30% of patients do not have a favorable response. The big question is how to determine predictors of response. AIMS: To identify baseline characteristics that might influence echocardiographic response to CRT. METHODS AND RESULTS: We performed a prospective single-center hospital-based cohort study of consecutive HF patients selected to CRT (NYHA class II-IV, left ventricular ejection fraction (LVEF) <35% and QRS complex ≥120 ms). Responders were defined as those with a ≥5% absolute increase in LVEF at six months. Clinical, electrocardiographic, laboratory, echocardiographic, autonomic, endothelial and cardiopulmonary function parameters were assessed before CRT device implantation. Logistic regression models were used. Seventy-nine patients were included, 54 male (68.4%), age 68.1 years (standard deviation 10.2), 19 with ischemic etiology (24%). At six months, 51 patients (64.6%) were considered responders. Although by univariate analysis baseline tricuspid annular plane systolic excursion (TAPSE) and serum creatinine were significantly different in responders, on multivariate analysis only TAPSE was independently associated with response, with higher values predicting a positive response to CRT (OR=1.13; 95% CI: 1.02-1.26; p=0.020). TAPSE ≥15 mm was strongly associated with response, and TAPSE <15 mm with non-response (p=0.005). Responders had no TAPSE values below 10 mm. CONCLUSION: From a range of clinical and technical baseline characteristics, multivariate analysis only identified TAPSE as an independent predictor of CRT response, with TAPSE <15 mm associated with non-response. This study highlights the importance of right ventricular dysfunction in CRT response. ClinicalTrials.gov identifier: NCT02413151.

Global and regional patterns of longitudinal strain in screening for chemotherapy-induced cardiotoxicity. / Importância da deformação longitudinal na deteção da cardiotoxicidade induzida por quimioterapia e na identificação de padrões específicos de afetação segmentar.

INTRODUCTION: Serial echocardiographic assessment of left ventricular ejection fraction (LVEF) is the gold standard in screening for chemotherapy-induced cardiotoxicity (CIC). Measurement of myocardial deformation using speckle tracking enables more detailed assessment of myocardial contractility. The aim of this study was to determine the relationship between global and regional longitudinal strain and CIC. METHODS: This was a prospective study of 158 breast cancer patients undergoing chemotherapy with anthracyclines with or without adjuvant trastuzumab who underwent serial monitoring by transthoracic echocardiography with assessment of myocardial deformation. CIC was defined as a decrease in LVEF to <53%. Global longitudinal strain (GLS) was estimated using EchoPAC BT12 software on a GE Vivid E9 cardiac ultrasound system. Patients were classified according to the 2015 ASE/EACVI criteria as having impaired myocardial deformation when GLS was reduced (less negative), with a cutoff of -18%. RESULTS: During a mean follow-up of 5.4 months (1-48 months), the incidence of CIC was 18.9%. A decrease in GLS was observed during follow-up for the entire cohort (baseline GLS -20.1±3.5% vs. -18.7±3.4% at last follow-up assessment, p=0.001). A total of 97 patients (61.4%) were observed to have impaired myocardial deformation (GLS ≥18%) at some point during follow-up. This decrease was more significant in patients who eventually developed CIC (GLS -17.2±2.5%, p=0.02). On analysis of regional strain, impaired contractility was observed in the septal (6 out of 6) and anterior (2 out of 3) segments. Multivariate logistic regression showed that patients who developed impaired longitudinal strain had a 4.9-fold increased risk of developing CIC (odds ratio 4.88, confidence interval 1.32-18.0, p=0.017). CONCLUSIONS: Worsening of myocardial deformation as assessed by speckle tracking is common in breast cancer patients undergoing chemotherapy, with predominantly septal and anterior wall involvement. Impaired myocardial deformation was independently associated with increased incidence of CIC.

Contribution of Dobutamine Stress Echocardiography to the Diagnosis and Prognosis of Low-Flow/Low-Gradient Aortic Stenosis.

BACKGROUND: Aortic valve replacement (AVR) is the treatment of choice in patients with severe symptomatic aortic stenosis (AS). Patients with a low left ventricular ejection fraction (LVEF) represent a challenge for evaluation and therapeutic decision. Dobutamine stress echocardiography (DSE) allows the distinction to be made between fixed low-flow/low-gradient (LF/LG) AS and pseudosevere AS. METHODS: Between 2001 and 2014 a retrospective analysis was conducted of patients who underwent DSE to investigate severe AS. DSE was performed in 3- to 5-min steps up to a maximum dose of 20 µg/kg/min. Parameters evaluated at baseline and at each step of DSE included: left ventricular enddiastolic volume (LVEDV) and left ventricular endsystolic volume (LVESV), maximum gradient (MaxG), mean gradient (MG) and aortic valve area (AVA). AS was considered to be severe if the AVA at peak dose was ≤1 cm2. Patients were allocated to two groups according to their therapy: group 1 received only medical treatment, while group 2 underwent AVR. The average follow up was 51.5 ± 4.4 months. RESULTS: A total of 41 patients (28 males, 13 females; mean age 71.7 ± 8.3 years) was analyzed. Severe AS was diagnosed in 34 patients (83%). Baseline echocardiographic characteristics were: AVA 0.7 ± 0.2 cm2, MaxG 42.0 ± 9.1 mmHg, MG 25.6 ± 6.4 mmHg, LVEF 33.1 ± 8.4%, LVEDV 149.6 ± 44.5 ml, and LVESV 104.0 ± 42.6 ml. At peak DSE, AVA was 0.8 ± 0.2 cm2, MaxG 62.7 ± 18.2 mmHg, MG 38.1 ± 11.6 mmHg, LVEF 42.2 ± 9.9%, LVEDV 142.6 ± 43.85 ml, and LVESV 89.7 ± 37.4 ml. Nineteen patients were allocated to group 1, and 22 to group 2. In group 2, two patients underwent transcatheter aortic valve implantation (TAVI) and 20 had surgery. Mortality in group 1 was significantly higher than in group 2 (78.9% versus 27.3%). A Cox proportional hazard model analysis showed that no-intervention was the only predictor of mortality (unadjusted to age; hazard ratio (HR) 5.13, 95% confidence interval (CI) 1.96-13.44, p = 0.001; adjusted to age - HR 4.01, 95% CI 1.46-11.01, p = 0.007). CONCLUSIONS: LF/LG AS has a poor prognosis without intervention. DSE allows the lesion severity to be established. In the present study intervention was a predictor of survival during follow up.

Antiphospholipid syndrome: a recurrent cardiac thromboembolic insult in spite of optimal anticoagulation / Síndrome antifosfolípido: lesión tromboembólica cardiaca recurrente a pesar de anticoagulación óptima

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Multiple mechanical complications in ST-segment elevation myocardial infarction with angiographically normal coronary arteries.

This case report discusses an unusual presentation of ST-segment elevation myocardial infarction (STEMI) with normal coronary arteries and severe mechanical complications successfully treated with surgery. An 82-year-old man presented STEMI with angiographically normal coronary arteries and no major echocardiographic alterations at discharge. At the first month follow-up, he complained of fatigue and dyspnea, and contrast echocardiography complemented by cardiac magnetic resonance imaging revealed a large left ventricular apical aneurysm with a thrombus communicating by two jets of a turbulent flow to an aneurysmatic formation of the right ventricular apex. The patient underwent a Dor procedure, which was successful. Ventricular septal defects and ventricular aneurysms are rare but devastating complications of STEMI, with almost all patients presenting multivessel coronary artery disease. Interestingly in this case, the angiographic pattern was normal.