New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review.

This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of ß-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.

Multimodal assessment of acute cardiac toxicity induced by thoracic radiotherapy in cancer patients. Study protocol.

BACKGROUND: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage. METHODOLOGY: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage. DISCUSSION: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.

Rho-kinase pathway activation and apoptosis in circulating leucocytes in patients with heart failure with reduced ejection fraction.

BACKGROUND: Increased Rho-kinase activity in circulating leucocytes is observed in heart failure with reduced ejection fraction (HFrEF). However, there is little information in HFrEF regarding other Rho-kinase pathway components an on the relationship between Rho-kinase and apoptosis. Here, Rho-kinase activation levels and phosphorylation of major downstream molecules and apoptosis levels were measured for the first time both in HFrEF patients and healthy individuals. METHODS: Cross-sectional study comparing HFrEF patients (n = 20) and healthy controls (n = 19). Rho-kinase activity in circulating leucocytes (peripheral blood mononuclear cells, PBMCs) was determined by myosin light chain phosphatase 1 (MYPT1) and ezrin-radixin-moesin (ERM) phosphorylation. Rho-kinase cascade proteins phosphorylation p38-MAPK, myosin light chain-2, JAK and JNK were also analysed along with apoptosis. RESULTS: MYPT1 and ERM phosphorylation were significantly elevated in HFrEF patients, (3.9- and 4.8-fold higher than in controls, respectively). JAK phosphorylation was significantly increased by 300% over controls. Phosphorylation of downstream molecules p38-MAPK and myosin light chain-2 was significantly higher by 360% and 490%, respectively, while JNK phosphorylation was reduced by 60%. Catecholamine and angiotensin II levels were significantly higher in HFrEF patients, while angiotensin-(1-9) levels were lower. Apoptosis in circulating leucocytes was significantly increased in HFrEF patients by 2.8-fold compared with controls and significantly correlated with Rho-kinase activation. CONCLUSION: Rho-kinase pathway is activated in PMBCs from HFrEF patients despite optimal treatment, and it is closely associated with neurohormonal activation and with apoptosis. ROCK cascade inhibition might induce clinical benefits in HFrEF patients, and its assessment in PMBCs could be useful to evaluate reverse remodelling and disease regression.

Rho kinase cascade activation in circulating leukocytes in patients with diabetes mellitus type 2.

BACKGROUND: The intracellular ROCK signaling pathway is an important modulator of blood pressure and of cardiovascular and renal remodeling when Rho-kinase activity is increased. Besides, in preclinical models of diabetes, ROCK activation has also a role in abnormal glucose metabolism as well as in subsequent vascular and myocardial dysfunction. In humans, there are a few data assessing ROCK activation in patients with type 2 diabetes mellitus (T2D) and no studies assessing upstream/downstream components of the ROCK pathway. We assessed here levels of ROCK activation and some of the RhoA/ROCK cascade molecules in peripheral blood mononuclear cells (PBMCs) in T2D patients under current treatment. METHODS: Cross-sectional observational study comparing 28 T2D patients under current antidiabetic treatment with 31 consecutive healthy subjects, matched by age and gender. Circulating levels of malondialdehyde, angiotensin II and inflammatory cytokines IL-6 and IL-8 were determined in all subjects. ROCK activation in PMBCs, upstream and downstream cascade proteins, and levels of the proinflammatory molecules VCAM, ICAM-1 and IL-8 were determined in their PMBCs by Western blot. RESULTS: Compared to healthy controls, ROCK activation in T2D patients measured by 2 direct ROCK targets in PBMCs was increased by 420 and 570% (p < 0001) and it correlated significantly with serum glucose levels. p38 MAPK phosphorylation (downstream from ROCK) and JAK-2 (upstream from ROCK) were significantly higher in the T2D patients by 580% and 220%, respectively. In T2D patients, significantly increased PBMC levels of the proinflammatory molecules VCAM-1, ICAM-1 and IL-8 were observed compared to control subjects (by 180%, 360% and 260%, respectively). Circulating levels of Ang II and MDA were significantly higher in T2D patients by 29 and 63%, respectively. CONCLUSIONS: T2D patients under treatment with glucose-lowering drugs, antihypertensive treatment as well as with statins have significantly increased ROCK activation in their circulating leukocytes along with higher phosphorylation of downstream cascade proteins despite pharmacologic treatment, along with increased plasma angiotensin II and MDA levels. ROCK inhibition might have an additional role in the prevention and treatment of T2D.

Early left atrial dysfunction is associated with suboptimal cardiovascular health.

AIMS: Two-dimensional speckle-tracking echocardiography can assess left atrial (LA) function by measuring atrial volumes and deformation parameters (strain, strain rate). This cross-sectional analysis explores the association between ideal CV health (CVH), LA function, and systemic biomarkers in healthy individuals from the Chilean MAUCO Cohort. METHODS: We enrolled 95 MAUCO participants with different levels of CVH (mean age: 51 ± 8 years). We categorized participants into low or high CVH groups: A: 0-2, or B: 3-6 CVH risk factors. 2D echocardiography, glucose, insulin, total cholesterol, triglycerides, proBNP, hsCRP, insulin resistance index (HOMA), and right and left atrial strain (RASs and LASs, respectively) were determined. RESULTS: LASs was lower in Group A, while systolic and diastolic blood pressure (BP), body mass index (BMI), insulin, HOMA, total cholesterol, triglycerides, and LV and RV end-diastolic volume were significantly higher in Group A than Group B (P < .01). Change in LASs was inversely correlated with insulin (P = .040), HOMA (P = .013), total cholesterol (P = .039), glycemia (P = .018), and BMI (P = .0.037). CONCLUSION: LASs during the reservoir phase was diminished in subjects with a lower level of CVH. Higher insulin, HOMA, total cholesterol, glycemia, and BMI values were associated with decreased LA deformation during the reservoir phase. Morphofunctional alterations of the LA were also identified in the group with suboptimal CVH, as well as BP values in the range of hypertension. LA dysfunction in an asymptomatic population, along with metabolic syndrome, could be an early event in the continuum of CV damage.

Reliability of NIRS portable device for measuring intercostal muscles oxygenation during exercise.

This study assessed the intra-individual reliability of oxygen saturation in intercostal muscles (SmO2-m.intercostales) during an incremental maximal treadmill exercise by using portable NIRS devices in a test-retest study. Fifteen marathon runners (age, 24.9 ± 2.0 years; body mass index, 21.6 ± 2.3 kg·m-2; V̇O2-peak, 63.7 ± 5.9 mL·kg-1·min-1) were tested on two separate days, with a 7-day interval between the two measurements. Oxygen consumption (V̇O2) was assessed using the breath-by-breath method during the V̇O2-test, while SmO2 was determined using a portable commercial device, based in the near-infrared spectroscopy (NIRS) principle. The minute ventilation (VE), respiratory rate (RR), and tidal volume (Vt) were also monitored during the cardiopulmonary exercise test. For the SmO2-m.intercostales, the intraclass correlation coefficient (ICC) at rest, first (VT1) and second ventilatory (VT2) thresholds, and maximal stages were 0.90, 0.84, 0.92, and 0.93, respectively; the confidence intervals ranged from -10.8% - +9.5% to -15.3% - +12.5%. The reliability was good at low intensity (rest and VT1) and excellent at high intensity (VT2 and max). The Spearman correlation test revealed (p ≤ 0.001) an inverse association of SmO2-m.intercostales with V̇O2 (ρ = -0.64), VE (ρ = -0.73), RR (ρ = -0.70), and Vt (ρ = -0.63). The relationship with the ventilatory variables showed that increased breathing effort during exercise could be registered adequately using a NIRS portable device.

Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1-9) through an AT2R and Akt-dependent mechanism.

Angiotensin-(19), a peptide of the non-classical renin angiotensin system, has been shown to prevent and revert hypertension and cardiac hypertrophy. We hypothetized that systemic delivery of angiotensin-(1-9) following myocardial infarction will also be protective and extend to provide protection during reperfusion of the ischemic heart. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation and treated with angiotensin-(1-9) via osmotic mini-pump for 2 weeks in the presence or absence of Mas receptor or AT2R antagonists (A779 and PD123319, respectively). Myocardial death and left ventricular function were evaluated after infarction. Infarct size and functional parameters were determined in isolated rat hearts after global ischemia/reperfusion in the presence of angiotensin-(1-9) plus receptor antagonists or Akt inhibitor at reperfusion. in vitro, neonatal rat ventricular cardiomyocytes underwent simulated ischemia/reperfusion and angiotensin-(1-9) was co-incubated with A779, PD123319 or Akt inhibitor. Systemic delivery of angiotensin-(1-9) significantly decreased cell death and improved left ventricular recovery after in vivo myocardial infarction. Perfusion with the peptide reduced the infarct size and improved functional recovery after ex vivo ischemia/reperfusion. In vitro, angiotensin-(1-9) decreased cell death in isolated neonatal rat ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. The cardioprotective effects of angiotensin-(1-9) were blocked by PD123319 and Akti VIII but not by A779. Angiotensin-(1-9) limits reperfusion-induced cell death by an AT2R- and Aktdependent mechanism. Angiotensin-(1-9) is a novel strategy to protect against cardiac ischemia/reperfusion injury.

Increased active phase atrial contraction is related to marathon runner performance.

PURPOSE: Left atrial (LA) contraction is essential for left ventricular (LV) filling during exertion. We sought to evaluate the relationship of LA contraction and exercise capacity in trained athletes. METHODS: Sixteen male marathon runners were recruited and allocated into two groups according to their previous training status (≥ or < 100 km peer week). All subjects underwent a baseline cardiopulmonary test to evaluate maximal aerobic capacity and a transthoracic echocardiography previous and immediate post-marathon. LA contractile function evaluation was accomplished by measuring the negative deformation of the post P wave strain curve (LASa). LASa change was defined as LASa pre-marathon minus LASa immediate post-marathon. RESULTS: Mean age was 39 ± 6 years. LA volume index (39 ± 13 vs. 31 ± 5 mL/m2, p = 0.04), LV mass index (91 ± 21 vs. 73 ± 12 g/m2, p = 0.04), VO2 max (59 ± 3 vs. 50 ± 8 mL/kg/min, p = 0.036) were higher in more intensive trained group and marathon time was lower (185 ± 14 vs. 219 ± 24 min, p = 0.017). An increase in LASa after immediate post-marathon was observed in both groups, which was significantly greater in the highly trained group (18.9 ± 5.8 vs. 6.3 ± 3.5%, p < 0.003). Maximum VO2 measured previous to the marathon was inversely related to marathon time and directly correlated to LASa change (rho = 0.744, p = 0.001, rho = 0.546, p = 0.028, respectively). CONCLUSIONS: Athletes with more intensive training load have larger LV mass and LA size. An increase in LA contraction was seen post-marathon, which was significantly greater in the highly trained group. This increase in the LA contraction was related to the maximum VO2 measured previous to the marathon and to performance in a highly demanding test.

"Gigantic" biatrial myxoma with right heart functional impairment.

Cardiac myxomas are frequently located in the left or right atria, with multiple locations being rare. We report a 59-year-old healthy female with 5 months of cough and exertional dyspnea. A transthoracic echocardiography (TTE) exhibits a 9 × 5 cm nonpedunculated tumor arising from the interatrial septum (IAS) and inhabiting both atria, but was unable to depict the relation with the IAS. Transesophageal echocardiography exposes a single tumor crossing the IAS through an ostium secundum atrial septal defect (ASD) causing right heart functional impairment. Uneventful cardiac surgery allowed complete resection of the lesion and ASD closure. Pathology reported a myxoma.

[Cardiotoxicity of anticancer therapies. Towards the implementation of cardio-oncology units]. / Cardiotoxicidad inducida por tratamientos oncológicos. Fundamentos para la implementación de equipos de Cardio-Oncología.

Recently, we have witnessed major improvements in cancer treatment. Early diagnosis and development of new therapies have reduced cancer-related mortality. However, these new therapies, along with greater patient survival, are associated with an increase in untoward effects, particularly in the cardiovascular system. Although cardiotoxicity induced by oncologic treatments affects predominantly the myocardium, it can also involve other structures of the cardiovascular system, becoming one of the main causes of morbidity and mortality in those who survive cancer. The main objective of cardio-oncology is to achieve the maximum benefits of oncologic treatments while minimizing their deleterious cardiovascular effects. It harbors the stratification of patients at risk of cardiotoxicity, the implementation of diagnostic tools (imaging techniques and biomarkers) for early diagnosis, preventive strategies and early treatment options for the complications. Herein, we discuss the basic knowledge for the implementation of cardio-oncology units and their role in the management of cancer patients, the diagnostic tools available to detect cardiotoxicity and the present therapeutic options.

Influence of gender on right ventricle adaptation to endurance exercise: an ultrasound two-dimensional speckle-tracking stress study.

BACKGROUND: Characteristic right ventricle (RV) remodelling is related to endurance exercise in male athletes (MAs), but data in female athletes (FAs) are scarce. Our aim was to evaluate sex-related influence on exercise-induced RV remodelling and on RV performance during exercise. METHODS: Forty endurance athletes (>10 training hours/week, 50% female) and 40 age-matched controls (<3 h moderate exercise/week, 50% female) were included. Echocardiography was performed at rest and at maximum cycle-ergometer effort. Both ventricles were analysed by standard and speckle-tracking echocardiography. RESULTS: Endurance training induced similar structural and functional cardiac remodelling in MAs and FAs, characterized by bi-ventricular dilatation [~34%, left ventricle (LV); 29%, RV] and normal bi-ventricular function. However, males had larger RV size (p < 0.01), compared to females: RV end-diastolic area (cm2/m2): 15.6 ± 2.2 vs 11.6 ± 1.7 in athletes; 12.2 ± 2.7 vs 8.6 ± 1.6 in controls, respectively, and lower bi-ventricular deformation (RV global longitudinal strain (GLS) (%): -24.0 ± 3.6 vs -29.2 ± 3.1 in athletes; -24.9 ± 2.5 vs -30.0 ± 1.9 in controls, and LVGLS: -17.5 ± 1.4 vs -21.9 ± 1.9 in athletes; -18.7 ± 1.2 vs -22.5 ± 1.5 in controls, respectively, p < 0.01). During exercise, the increase in LV function was positively correlated (p < 0.01) with increased cardiac output (∆%LV ejection fraction, r = +0.46 and ∆%LVGLS, r = +0.36). Improvement in RV performance was blunted at high workloads, especially in MAs. CONCLUSION: Long-term endurance training induced similar bi-ventricular remodelling in MAs and FAs. Independently of training load, males had larger RV size and lower bi-ventricular deformation. Improvement in RV performance during exercise was blunted at high workloads, especially in MAs. The potential mechanisms underlying these findings warrant further investigation.

Big thrombus "sitting" in an atrial septal aneurysm.

A 79 year-old-man presented three episodes of upper gastrointestinal bleeding and weight loss. Endoscopy revealed bleeding and extrinsic compression at the pyloric region. Computed tomography scan showed a pancreatic tumor, peritoneal carcinomatosis, vascular infiltration, and incidentally found a partially calcified hypodense lesion of 35 mm in the left atrium, suggesting a myxoma or a thrombus. Echocardiography revealed moderate left atrium enlargement, dilated left atrial appendage with spontaneous echo contrast, moderate dilatation and dysfunction of the left ventricle, ejection fraction was 39%, and an atrial septal aneurysm in which a piriform, mass of 35×33×25 mm, was "sitting," suggesting an organized thrombus.

Acute effect of iloprost inhalation on right atrial function and ventricular dyssynchrony in patients with pulmonary artery hypertension.

BACKGROUND: Right atrium function and ventricular function have significant prognostic value in pulmonary arterial hypertension patients. Acute changes in right ventricular synchrony and right atrium function postiloprost inhalation have not been evaluated. METHODS: Cross-sectional study. Consecutive pulmonary arterial hypertension patients (group I from Nice classification) were included. Echocardiographic right atrium and right ventricular function pre- and postiloprost inhalation, including a right ventricular dyssynchrony index and right atrium function using speckle tracking, were performed in all patients. RESULTS: Twenty pulmonary arterial hypertension patients, 44±7 years and 90% females, were included. After iloprost inhalation, we observed a significant increment in right ventricular fractional area change and a significant decrease in right ventricular dyssynchrony index (21.4±5.6% vs 26.1±4.0 %, P=.007 and 79±44 vs 32±22 mseconds, P<.01, respectively), also an improvement in right atrium reservoir function (8.6±3.1% vs 11.7±3.5 %, P=.002). CONCLUSIONS: Iloprost inhalation induces acute changes in right ventricular function, dyssynchrony, and right atrium performance that may add relevant clinical information in the management and risk stratification of pulmonary arterial hypertension patients.

Atrial Function Assessed by Speckle Tracking Echocardiography Is a Good Predictor of Postoperative Atrial Fibrillation in Elderly Patients.

OBJECTIVE: Advanced age is an independent predictor of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass surgery. We evaluated whether left atrial (LA) dysfunction assessed by strain contributes to identifying elderly patients prone to POAF. METHODS: Case-control study of 70 subjects undergoing coronary artery bypass surgery. Clinical and laboratory characteristics were recorded at baseline and 72 hours after surgery. Echocardiography was performed during the preoperative period; LA dimensions and deformation by strain (systolic wave [LASs]) as well as strain rate (systolic wave [LASRs] and atrial contraction wave [LASRa]) were assessed. RESULTS: Postoperative atrial fibrillation occurred in 38.5% of patients within the first 72 hours after surgery (28.5% of the younger vs. 48.6% of the older group). Baseline and postoperative inflammatory markers as well as total surgical and aortic clamp time were similar between groups. LA function was markedly impaired in subjects with POAF. Age correlated with LASs, LASRs, and LASRa. These associations remained consistent when subjects 75 years or older were considered separately. Both LASs and LASRa for patients with or without POAF, respectively, were significantly impaired in elderly subjects with POAF. Multivariate analysis provided further evidence that both LASs and age are independent predictors for POAF. CONCLUSION: Age-related changes in atrial function preceding atrial dilation are evident only upon LA strain analysis. LA strain impairment is an independent predictor of POAF irrespective of age and may serve as a surrogate marker for biological processes involved in establishing the substrate for POAF.

[Large mitral annulus myxoma presenting with syncope: Report of one case]. / Síncope secundario a mixoma gigante del anillo mitral: Reporte de un caso.

We report a 23-year-old woman, with three recent exertional syncopes. Transthoracic (TTE) and transesophageal (TEE) echocardiography found a large heterogeneous mass (38 x 35 mm) arising from the posterior mitral annulus, protruding in systole through the left ventricular outflow tract (LVOT). Heart MRI confirmed the echocardiography findings, suggesting a cardiac myxoma. Cardiac surgery accomplished the complete resection of the lesion, confirming a mass arising from the posterior mitral annulus and preserving mitral anatomy and function. Pathology was positive for a myxoma. Uneventful evolution allowed the discharge of the patient at the fifth postoperative day. Control TTE discarded any complication.

[Survival of patients with pulmonary arterial hypertension after the advent of specific pulmonary vasodilator therapies]. / Sobrevida a mediano plazo en los pacientes con hipertensión arterial pulmonar en la era de terapias vasodilatadoras específicas del territorio vascular pulmonar.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Long-term survival remains poor despite of advances in specific vasodilator therapy. AIM: To describe the survival rate in a cohort of PAH patients in two referral centers in Chile. PATIENTS AND METHODS: One hundred fifteen patients aged 43 ± 15.6 years (85% females) with PAH qualified for this study. Their median pulmonary artery pressure was 55.4 ± 14 mmHg and their six minutes walking capacity was 368 ± 119 m. They were followed for 58 ± 0.4 months and their actual survival rates were compared with the estimated survival using the equation proposed by the French registry of PAH. RESULTS: One, two and three year survival rates were 97, 94 and 89%, respectively. The observed survival rates were greater than the estimated survival. CONCLUSIONS: The improvement in survival rates observed in this cohort of patients is similar to what has been described in literature.

Interatrial Dyssynchrony May Contribute to Heart Failure Symptoms in Patients with Preserved Ejection Fraction.

PURPOSE: Heart failure (HF) with preserved ejection fraction (HFPEF) is the most prevalent type of HF in nonhospitalized patients, but its pathophysiology remains poorly understood. The aim of our study was to assess the existence of interatrial dyssynchrony (IAD), a potentially treatable condition, in the development of HF symptoms. METHODS: Consecutive patients with new onset of shortening of breath, referred for suspected HF, were screened. In all cases, a transthoracic echocardiography, ECG, and determination of plasma BNP level were performed at initial consultation. Patients were diagnosed according to current guidelines. Patients with HF and reduced ejection fraction were excluded. Later, the time from P-wave onset on the ECG to peak negative strain (atrial contraction) was determined using speckle tracking echocardiography; the time difference between both atria (ms) was used as an index of IAD. RESULTS: Sixty-six patients were included. Mean age was 74 ± 8 years (74% female, 77% hypertensive). HFPEF patients (n = 32) showed an increased IAD as compared to subjects with non-HF (n = 34; interatrial time difference 72.7 ± 27 vs. 28 ± 7 ms, P < 0.001). IAD showed a significant correlation with BNP levels, diastolic pattern, and echocardiographic parameters indicative of elevated LV filling pressures. LA function assessed by LA strain rate was not significantly different between HPPEF patients with and without IAD > 60 ms. CONCLUSIONS: We showed that IAD was present at initial stages of symptomatic HFPEF. It might be an important mechanism involved in the development of symptoms in HFPEF and a potential target amenable to be treated with device therapy.

Effect of cardiac resynchronization therapy on left ventricular diastolic function: implications for clinical outcome.

Background: The definition of response to cardiac resynchronization therapy (CRT) remains controversial,with variable rates of response depending on the criteria used. Our aim was to analyze the impact of CRT on diastolic function in different degrees of response, particularly in patients with positive clinical but no echocardiographic response.Methods and Results: In 250 CRT patients clinical evaluation and echocardiography were performed before and after CRT. Absolute response to CRT was defined as a reduction in left ventricular (LV)end-systolic volume of ≥ 15% at 1-year follow-up. Additionally, patients were classified into 4 subgroups according to their amount of response: extensive reverse remodeling (RR), slight RR, clinical response without RR, and neither clinical response nor RR. An improvement in estimates of LV filling pressure and a decrease in left atrial dimensions were observed only in responders to CRT. Patients with clinical but no echocardiographic response had significant improvement in E-wave and deceleration time and nonsignificant improvement in other parameters.Conclusions: LV diastolic function improves with CRT. Clinical responders without echocardiographic response show improvement in parameters of diastolic function. That suggests that clinical-only response to CRT is secondary to a real effect of the therapy, rather than a placebo effect.

Atrial functional and geometrical remodeling in highly trained male athletes: for better or worse?

PURPOSE: Highly trained athletes have an increased risk of atrial arrhythmias. Atrial geometrical and functional remodeling may be the underlying substrate. We analyze and relate atrial size, deformation and performance in professional handball players compared with non-sportive subjects. METHODS: 24 Professional handball players and 20 non-sportive males were compared. All subjects underwent an echocardiographic study with evaluation of left (LA), right atrial (RA) dimensions and deformation by strain (Sa) and strain rate (SRa). Atrial performance was assessed from the atrial stroke volume (SV). With computational geometrical models, we studied the relation between atrial volumes, strains and SV and compared atrial working conditions. We estimated the functional reserve and a resulting average wall stress. RESULTS: LA and RA volumes were larger in athletes than in controls (35.2 ± 8.8 vs. 24.8 ± 4.3 ml/m(2), p < 0.01 and 29.0 ± 8.4 vs. 19.0 ± 5.1 ml/m(2), p < 0.01 respectively). LASa and RASa during active atrial contraction were decreased in athletes (-12.2 ± 2.0 vs. -14.5 ± 2.1%, p < 0.01 and -12.1 ± 1.8 vs. -14.2 ± 1.5%, p < 0.01 respectively). LASV was similar between groups (6.6 ± 1.4 vs. 7.3 ± 1.1 ml, p = 0.19) and RASV was lower in athletes (6.2 ± 1.3 vs. 7.2 ± 1.1 ml, p < 0.01). Computational models showed that this different operational mode potentially increases performance reserve, but at the cost of higher atrial wall stress. CONCLUSION: A proportion of athletes with enlarged LA and RA showed different atrial contractile performance, likely resulting in atria working at higher wall stress.

[Tricuspid and pulmonary valve involvement in carcinoid syndrome. Report of two cases]. / Síndrome carcinoide y compromiso valvular cardiaco, a propósito de 2 casos.

Carcinoid is a rare neuroendocrine tumor typically arising in the gastrointestinal tract that can cause heart valve involvement. We report two patients with carcinoid syndrome and tricuspid/pulmonary valve lesions. A 33-year-old male presenting with fatigue and weight loss: A tumor in the tail of the pancreas was found on an abdominal CAT scan. The percutaneous biopsy was informed as a carcinoid tumor. A trans-esophageal echocardiogram showed a tricuspid and pulmonary valve involvement, which was replaced surgically. The biopsy informed an extensive fibrous and myxoid degeneration of the valves. A 35-year-old male with a carcinoid syndrome and cardiac failure: An echocardiogram showed a severe tricuspid stenosis and severe pulmonary regurgitation. The patient was subjected to a double surgical valve replacement. The pathology report of the excised valve showed a deforming fibrous and myxoid valvulopathy.