Thromboembolic events due to left atrial appendage (LAA) thrombosis are the main complication of non-valvular atrial fibrillation (NVAF). Although anticoagulants are effective in patients with NVAF, a minimal residual thromboembolic risk persists. Little is known about the prevalence of LAA thrombus and the rate of resolution after the recommended period of anticoagulation therapy, including vitamin K antagonists (VKA), heparin, and non-vitamin K antagonist oral anticoagulants (NOACs).We aimed to study the prevalence of LAA thrombus in an unselected cohort of patients undergoing transesophageal echocardiogram (TEE), and the determinants of LAA thrombus resolution. We retrospectively analyzed 8888 consecutive TEEs performed over five years in two high-volume centers and included all patients with LAA thrombus. A total of 265 patients (3%) had an LAA thrombus. Among these, 97% presented with AF. Fifty-eight percent of patients were on anticoagulants at least three weeks before the diagnosis. After the LAA thrombus diagnosis, VKAs were prescribed in 52%, heparin in 18.5%, and NOAC in 27% of patients. Among the 183 patients with repeat TEE, performed at (25-75th) 39 days (21-84), 67% showed resolution of the LAA thrombus. Although the rate of thrombus resolution was higher in patients treated with NOACs (NOACs 71%, VKA 66%, Heparin 60%) the difference between anticoagulants was statistically non-significant (VKA, OR 0.9, p = 0.83; NOAC, OR 1.23, p = 0.42; heparin, OR 0.69, p = 0.35). Thus, NOACs were demonstrated to be at least as effective as other anticoagulants in the rate of LAA thrombus resolution. Upon multivariate-adjusted analysis, higher LAA emptying velocities were the only predictor of thrombus resolution. In conclusion, the majority of patients were already on anticoagulants. NOACs could be at least as effective as other anticoagulants, yielding an LAA thrombus resolution in two-thirds of patients. This may have clinical relevance, especially in patients undergoing cardioversion or catheter ablation.
Background: Tako-tsubo syndrome (TTS) in its most typical form shares common features with anterior ST segment elevation myocardial infarction (AMI) during acute presentation. Differential diagnosis between the two conditions is often challenging especially if ST segment elevation is associated with extensive apical akinesis. Methods : we sought to systematically analyze ECG and echocardiographic parameters including LV longitudinal strain and two new indexes: the inferior-apex ratio (IAR) and the inferior-lateral-apex ratio (ILAR), to assess if ventricular involvement may be different in TTS and AMI. Results : A retrospective cohort study was conducted with 2 groups: patients with TTS (n=22) and patients with extensive anterior STEMI (n=22). Lack of ST elevation in V1 was associated with TTS with sensitivity and specificity of 86%, positive and negative predictive value of 86%. Longitudinal strain in mid inferior and mid inferior-lateral segments were more compromised in TTS: - 4.3±6.4% and -5.4± 5.4% in TTS vs -10.2±5.5% and -9.9 ±4.9% in AMI, respectively (P<0.01 for all). By multivariate analysis, both longitudinal strain values, inferior-apical ratio (IAR) <1 and inferior-lateral-apical ratio (ILAR) <1 were independently associated with diagnosis of TTS during acute phase. Conclusions : our results suggest that impaired contractility extending beyond apex to mid inferior and inferior-lateral walls can be easily assessed by IAR and ILAR, and these indexes facilitate non-invasive differentiation of TTS from extensive anterior STEMI.
Heart failure (HF) is common, and HF with preserved ejection fraction (HFpEF) has become its most frequent clinical presentation because of ageing of the population and decreasing prevalence of coronary artery disease (CAD).1, 2 An analysis of all studies using echocardiography to estimate the prevalence of cardiac dysfunction in subjects aged ≥60 years showed a median prevalence of 36.0% (range 15.8–52.8%) and 5.5% (range 3.3–9.2%) for 'isolated' left ventricular (LV) diastolic dysfunction and LV systolic dysfunction, respectively, and a median prevalence of 4.9% (range 3.8–7.4%) and 3.3% (range 2.4–5.8%) for symptomatic HFpEF and HF with reduced ejection fraction (HFrEF).3 Outcomes of patients with HF remain poor. The European Society of Cardiology (ESC) HF Long-Term Registry collected data of 12 440 patients with HF, 59.5% outpatients and 40.5% hospitalized patients for acute HF (AHF), enrolled from 211 cardiology centres in 21 European and/or Mediterranean countries.4 The 1 year all-cause mortality rate was 6.4% for ambulatory patients and raised to 23.6% for those hospitalized for AHF. The combined endpoint of 1 year mortality or HF hospitalization occurred in 14.5% of outpatients and 36% of hospitalized patients. A primary care-based cohort study in Scotland compared the 5 year survival of patients with HF with that of the most common causes of cancer. The 5 year survival of patients with HF was of 55.8% in men and 49.5% in women, and it was better than that of patients with lung cancer, colorectal cancer, and, in women, ovarian cancer but worse than that of male patients with prostate cancer and of female patients with breast cancer.5 Temporal trends in hospitalization rates and outcomes of patients with HF were examined in multiple studies based on national databases from European countries. In general, all studies confirm better survival of patients with a new diagnosis of HF. Hospitalization rates have more variable trends because of the opposing influence of the increase in the absolute number of HF patients and their better outcome. The most optimistic data came from Denmark. In this country, the standardized annual rate of HF hospitalizations decreased by an average of 3.5% each year, starting from the year 2000, and the 1 and 5 year mortality rates declined from 45 to 33% and from 59 to 43%, respectively, in the years 2008–2012, compared with the years 1983–1987.6 In contrast, in France, despite a decrease in mortality rates by 3.3% each year, from 2000 to 2010, HF hospitalization rates remained stable. Sex differences were also noted with a lower decrease in HF hospitalizations and a larger decrease in mortality rates in men vs. women.7 Data from Germany and from Slovenia show an increase in HF hospitalizations, mostly related with ageing of the general population. In Germany, the absolute number of HF-related hospitalizations increased by 65.4%, 28.4% after age standardization, in the year 2013, compared with 2000. Accordingly, the absolute number of HF-related hospital days increased by 22.1%, despite a 25.9% decrease in the average length of stay from 14.3 to 10.6 days. In-hospital mortality rates also remained high (9.3% in 2013). These trends of increased HF hospitalizations and high in-hospital mortality rates affected mostly the patients aged >65 years.8 The role of age is shown also by the data collected in Slovenia where age-standardized HF hospitalization rates decreased by 7.1%, whereas the absolute number of HF hospitalizations increased by 19.8% between the years 2004 and 2012.9 Heart failure has a worldwide clinical impact. Geographical differences are therefore more and more important. Southeast Asia is home of a growing population of >600 million people with a relatively younger age, compared with Western countries. Subjects in Southeast Asia have a high prevalence of risk factors, particularly hypertension, smoking, physical inactivity, and diabetes, although a lower prevalence of overweight/obesity. Epidemiological trends in Singapore showed a sharp 38% increase in age-adjusted HF hospitalizations. Compared with patients in Western countries, these patients are younger and have high mortality rates, and HF treatment is still largely underused.10 Japan has the oldest population in the world with >25% of the population aged ≥65 years, and this has an impact on the growing prevalence of HF.11 The estimated prevalence of HF is ~1 million people in Japan and >4 million in China. Mortality rates after discharge from an HF hospitalization are lower in Japan than in Western countries with 1 year rates of 9–12%. The very long length of stay (15–21 days) of an HF hospitalization in Japan likely contributes to this finding.11-13 The new ESC HF guidelines have established new criteria for the diagnosis of HFpEF and HF with mid-range ejection fraction (HFmrEF). They are based on the presence of symptoms and/or signs of HF, an LV ejection fraction (EF) of 40–49% for HFmrEF and ≥50% for HFpEF, and signs of cardiac dysfunction, including high brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) plasma levels and signs of structural heart disease, LV hypertrophy, or left atrial dilatation, and/or of LV diastolic dysfunction, namely, an abnormal E/e′ ratio. These criteria remain, however, less simple than for HFrEF, and the diagnosis can be further complicated by the prominent role of co-morbidities. A diagnostic algorithm based on clinical and echo-Doppler criteria has recently been proposed.14 In symptomatic patients with normal LVEF and normal pulmonary artery wedge pressure (PAWP) at rest, right heart catheterization during exercise can unmask diastolic dysfunction showing an increase in PAWP during exercise.15 It is still debated whether an echocardiographic assessment can substitute invasive haemodynamic measurements during exercise.16, 17 Using resting and exercise haemodynamic data and cardiac imaging, Obokata et al.18 have described a distinct obese phenotype of HFpEF, characterized by worse exercise capacity, higher biventricular filling pressures during exercise, and reduced pulmonary artery vasodilator reserve. Abnormalities of LV systolic function can be found despite a normal EF. A reduced LV global longitudinal strain (GLS) with an increased LV circumferential strain was shown in HFpEF and was associated with higher PAWP.19 Measurement of LV longitudinal strain may be particularly useful in specific patients' groups at high risk for HF, such as those with valve disease or those undergoing chemotherapy.20, 21 The recent ESC HF guidelines have introduced the new category of HFmrEF. The authors wrote 'we believe that identifying HFmrEF as a separate group will stimulate research into the underlying characteristics, pathophysiology and treatment of this population'.2 Such a prophecy was fulfilled. The clinical characteristics and biomarker profiles of the patients with HFmrEF are, in general, intermediate between those of the patients with HFrEF and HFpEF. However, the prevalence of CAD is generally similar to that of patients with HFrEF.22-24 Outcomes of patients with HFmrEF are generally better than in patients with HFrEF and similar to that of HFpEF patients.23, 25 In contrast, the response to treatment seems similar to that of patients with HFrEF. In TOPCAT (Aldosterone Antagonist Therapy for Adults With HFpEF) trial, spironolactone reduced outcomes in patients with lower baseline LVEF (<50%).26 Similarly, in Candesartan Cilexetil in HF Assessment of Reduction in Mortality and Morbidity (CHARM), candesartan reduced the primary outcome also in patients with HFmrEF with an effect on recurrent HF hospitalizations that remained significant until EF was ≤60%.27 Beta-blockers improved LVEF and reduced untoward outcomes only in patients with reduced LVEF in an individual patient meta-analysis of previous controlled trials.28 Digoxin reduced HF hospitalizations and the composite endpoint of deaths and HF hospitalizations in patients with HFrEF, not significantly in those with HFpEF, and at an intermediate level in those with HFmrEF.29 Thus, it seems that HFmrEF is a 'milder form' of HFrEF including patients, mainly with CAD, who had only mild myocardial injury or who have recovered from more severe myocardial dysfunction. Consistently, these patients also have a better prognosis than those with HFrEF and, as the mechanisms of dysfunction are the same, respond to the same drugs active in patients with HFrEF. However, perhaps the greatest advantage of the introduction of the HFmrEF category is to highlight the different characteristics of patients with an LVEF ≥ 50%, a view shared also in the more recent Australian and New Zealand HF guidelines that use a cut-off of 50% to differentiate between HFrEF and HFpEF.30 Efforts have been dedicated to the identification of asymptomatic subjects at higher risk of HF development. Earlier initiation of medical therapy and better control of risk factors may prevent HF and, ultimately, improve survival in these patients.1, 2 Both echocardiographic parameters and biomarkers have been evaluated. In a large cohort of asymptomatic subjects ≥65 years old, with ≥1 HF risk factor, who underwent echocardiographic screening, Yang et al.31 found a prevalence of 13% for LV hypertrophy, 12% for an abnormal E/e′, 33% for an impaired GLS, and 31% for left atrial enlargement, and these parameters were independent predictors of new HF. Left ventricular mass and GLS, but not the other parameters, significantly reclassified individuals compared with traditional risk factors. Strategies based on NT-proBNP measurements were proven as effective for the prevention of HF development. Abouezzeddine et al.32 compared the predictive value for HF and major cardiac events of multiple biomarkers in a community cohort in Olmsted County. Only NT-proBNP and high sensitivity (hs) cardiac troponin T (cTnT) had an independent predictive value, compared with clinical variables. A strategy based on screening with NT-proBNP assays in the general population was cost-effective and compared favourably with established interventions.32 Body weight remains an important prognostic variable. According to the obesity paradox, increased body weight is associated with better outcomes. Body surface area might be preferred to body weight, and in the ESC HF Long-Term Registry, body surface area had an inverse relation with total and cardiovascular mortality but not with hospitalizations.33 Patients with morbid obesity do not have the same survival advantage of their obese or overweight counterparts.34 In the AHF Global Survey of Standard Treatment registry, body weight had a U-shaped relationship with mortality with the lowest values in overweight subjects. However, this relationship vanished after adjustment for covariates. Changes in body weight are also used to monitor fluid status in patients with decompensated HF. However, their sensitivity is lower compared with echocardiographic parameters and NT-proBNP plasma levels.35, 36 Cachexia, sarcopenia, and unintentional weight loss are associated with poorer outcomes.37 In addition, frailty, assessed as low physical activity, weight loss, slow walking speed, weak grip strength, and exhaustion, was an independent predictor of early disability, long-term mortality, and re-hospitalizations.38, 39 Blood pressure is another parameter with a paradoxical inverse relationship with outcomes in HF. In addition to absolute values, the changes in blood pressure may also have prognostic significance. A long-term reduction in systolic blood pressure greater than ±10 mmHg/year was associated with an increased risk of death or heart transplantation (1.8 and 2.0, respectively).40 Pulse pressure is related with vascular compliance as well as with cardiac output. In a cohort study of consecutive HFpEF patients, pulse pressure was significantly and positively correlated with pulse wave velocity and LV stroke volume index, and patients in the lowest (<45 mmHg) and the highest (>75 mmHg) pulse pressure quintiles had a significantly higher risk of cardiovascular and HF-related events.41 Heart rate is an independent predictor of mortality in HF. A resting heart rate >70–75 b.p.m. has been identified as a major risk factor for poorer outcomes in patients with HFrEF, AHF, and many other conditions, including cancer.42-44 Selective heart rate lowering in patients with HF is now indicated in the guidelines both from ESC, the USA, Australia, and New Zealand.2, 30, 45 Acute HF is associated with a dramatic increase in the risk of subsequent death or re-hospitalization.2 Many studies are focused on the prognostic stratification of these patients. Precipitating factors are important. In an observational study, precipitating factors were classified in four main groups: acute coronary syndrome, atrial fibrillation, acute pulmonary disease, and other causes. Atrial fibrillation and acute coronary syndrome were associated with more readmissions. Acute coronary syndrome and pulmonary disease were associated with higher mortality in the short term (1 week) and medium term (3 weeks), respectively.46, 47 Data from the ESC HF Long-Term Registry suggest that the clinical phenotype at admission can be used to stratify patients and predict 1 year mortality, being this higher in cardiogenic shock, right HF, pulmonary oedema, and decompensated HF than with acute coronary syndromes and hypertensive HF.48 Interestingly, patients who survived at least 6 months post-discharge represented a more homogeneous group, and their 1 year outcome was less influenced by their initial clinical profile or systolic blood pressure at admission.48 Worsening HF, an event occurring in 7–30% of patients during hospitalization, is associated with increased re-hospitalization and post-discharge mortality rates and has been used as an endpoint in clinical trials.12, 49, 50 Also, an increased length of stay may predict subsequent worse outcomes, although geographical differences may reduce its potential value as an endpoint for clinical trials.50 BIOSTAT-CHF (A systems BIOlogy Study to TAilored Treatment in Chronic HF) was a large, multicentre, prospective, observational study including 2516 patients from 11 European countries with worsening HF symptoms and 1738 patients from Scotland as validation cohort.51 Based on the variables collected, a risk score for outcomes was developed. The five strongest predictors of mortality were older age, higher blood urea nitrogen, high NT-proBNP, lower haemoglobin, and failure to prescribe a beta-blocker. The five strongest predictors of HF hospitalization were older age, previous HF hospitalization, peripheral oedema, lower systolic blood pressure, and lower estimated glomerular filtration rate.52 Imaging methods have been focused mainly on pulmonary hypertension, right ventricular (RV) function, and mitral regurgitation. These measurements are useful in both HFrEF and HFpEF. Pulmonary hypertension remains a major independent determinant of outcomes.53 Detection of increased pulmonary artery pressure (PAP) through wireless ambulatory monitoring is among the few procedures that has significantly reduced HF hospitalizations.54, 55 The 2015 ESC/ERS guidelines differentiate two different haemodynamic subsets of pulmonary hypertension due to left heart disease, based on levels of pulmonary vascular resistance and diastolic pressure gradient: isolated post-capillary pulmonary hypertension and combined post-capillary and pre-capillary pulmonary hypertension.56 The value of the diastolic pressure gradient is, however, controversial as it may become negative because of large V waves in PAWP tracings due to mitral regurgitation, and these patients may have a better outcome than those with combined pre-capillary and post-capillary pulmonary hypertension.57-59 Pulmonary hypertension and RV dysfunction are present in a significant proportion of patients with HFpEF.60 Their prevalence is 68% and 18–28%, depending on the measurement used. They were both associated with mortality in a systematic review and meta-analysis.61 Studies based on the assessment of RV function by cardiac magnetic resonance have also shown significant associations with outcomes in specific patient groups such as those with HFpEF.62 Echocardiographic parameters are often used as surrogates of LV and pulmonary pressures. However, a poor-to-moderate correlation was found among echocardiographic parameters (E/E′, isovolumetric relaxation time, left atrial reservoir strain, and RV wall thickness) and invasive haemodynamic measurement [PAWP, LV end-diastolic pressure (LVEDP), mean PAP, and PAP], independently from the presence of atrial fibrillation.16 Patients with atrial fibrillation had PAWP values higher than LVEDP, whereas PAWP was lower than LVEDP in patients in sinus rhythm.17 Right ventricular function, particularly when assessed with indexes that correct for pulmonary pressure, such as the tricuspid annular plane systolic excursion/systolic PAP ratio, the RV longitudinal strain/systolic PAP ratio, or the tricuspid annular plane systolic excursion × transtricuspid systolic gradient product, is independently related with mortality in addition to, or differently from, pulmonary hypertension alone. Its prognostic value is confirmed in both HFrEF and HFpEF, although its determinants differ. Improvement in RV function after treatment is predictive of better outcomes compared with persistent or worsened dysfunction during follow-up.63-65 Multiple novel biomarkers, assessing different mechanisms of HF, cell death, fibrosis, neurohormonal activation, inflammation, and other organ damage, have been introduced.66 To date, only natriuretic peptides are recommended in current ESC guidelines.2 They are sensitive markers of increased myocardial wall stress and hence increased LV diastolic pressure and congestion. However, their value is influenced by multiple variables among whom age and heart rhythm have a major role. Their diagnostic accuracy is reduced in elderly subjects.67 Atrial fibrillation causes an increase in BNP levels and reduces their sensitivity for the detection of changes induced by treatment.68 Lastly, two prospective randomized trials aimed at the evaluation of the clinical impact of serial measurements of BNP levels have failed to show beneficial effects on outcomes, likely because optimization of medical treatment occurred also in the control group.69, 70 Mid-regional pro-adrenomedullin (MR-proADM) is another marker related with myocardial stress. The Interdisciplinary Network HF programme enrolled 1022 patients hospitalized for acute systolic HF and followed them for 18 months. High MR-proADM was associated with more impaired LV function, higher co-morbidity burden, lower doses of HF medications, and lower likelihood of LV reverse remodelling. Compared with natriuretic peptides, MR-proADM had superior prognostic significance and improved Cox regression models including natriuretic peptides and was the only biomarker predicting also non-cardiac death. Six month MR-proADM enhanced models including baseline MR-proADM (P < 0.001) for prediction of all-cause death [net reclassification index: 0.48, 95% confidence interval (CI) 0.19–0.78]. Serial MR-proADM measurements after 6 months enhanced risk assessment. Cardiac troponin is a sensitive marker of myocardial injury, and its value for the prognostic assessment of patients with HF is now approaching that of natriuretic peptides. It is an independent predictor of cardiovascular outcomes in subjects at risk of cardiac disease as well as in HF patients either ambulatory or recently hospitalized.71-74 In a recent individual patient data meta-analysis including data from 10 studies and 9289 patients with chronic HF, hs cTnT was added to a prognostic model including established risk markers (sex, age, ischaemic vs. non-ischaemic aetiology, LVEF, estimated glomerular filtration rate, and NT-proBNP) and significantly improved risk prediction for all-cause and cardiovascular mortality and cardiovascular hospitalizations.75 Biomarkers allow the assessment of co-morbidities, such as kidney dysfunction and iron deficiency. Serum creatinine changes maintain a major role for the prognosis of patients with acute and chronic HF. Excessive diuresis, hypotension, and initiation of renin–angiotensin–aldosterone inhibitors may cause increases in serum creatinine unrelated with prognosis. These conditions must be considered for the interpretation of the serum creatinine changes.76-78 Cystatin C is useful for the detection of impaired glomerular filtration rate at an earlier stage, before serum creatinine increases.76 Markers of renal tubular function were studied for the early detection of tubular damage and kidney injury. In AHF, plasma kidney injury molecule-1 predicted HF re-hospitalization, while urinary kidney injury molecule-1, together with urinary neutrophil gelatinase-associated lipocalin, predicted the development of true worsening renal function.79, 80 The ESC HF guidelines mandate the assessment of iron deficiency through measurements of serum ferritin and transferrin saturation as its treatment may improve quality of life and exercise capacity and reduce hospitalizations in patients with HFrEF.2, 81-83 Each biomarker measures different pathways. A multi-marker strategy, based on new platforms that allow the measurement of up to 48 or 96 different biomarkers, allows the detection of the mechanisms involved in different patients with HF. For instance, network analysis of a panel of 48 different biomarkers in patients with AHF with or without diabetes showed a strong cluster of biomarkers related with inflammation and fibrosis, such as interleukin-6, periostin, and C-reactive protein (CRP), suggesting a specific activation of these pathways, in diabetic patients but not in non-diabetic patients.84 An analysis of the prognostic value of 44 different biomarkers in patients with AHF showed an 11% increase in C-index to 0.84 and 0.78 for 30 and 180 day all-cause mortality with the combination of blood urea nitrogen, chloride, interleukin-6, troponin I, soluble suppression of tumorigenicity-2 (sST2) and vascular endothelial growth factor receptor-1 into a clinical model.85 Serial measurements are also important and provide better prognostic assessment compared with baseline values only. A repeat measurement as early as Day 2 was adequate for NT-proBNP and cystatin C in terms of maximizing discriminatory accuracy, and further measurements on Days 14 and 60 provided added value for hs cTnT, growth differentiation factor-15, sST2, and hs CRP.86 Studies comparing new biomarkers with traditional ones and clinical assessment are still needed. Jackson et al.87 evaluated the incremental prognostic value of multiple novel biomarkers in 628 patients recently hospitalized with decompensated HF. At multivariable analysis, MR-proADM, hs cTnT, combined free light chains, hs CRP, and sST2 had additional prognostic value compared with traditional clinical signs and biomarkers.87 In another study, neither BNP nor cTnT measured at admission improved outcome prediction, compared with clinical data.88 MicroRNAs are another major area of research not only as potential targets of treatment but also as biomarkers. Plasma levels may have prognostic value in acute or chronic HF and may change after treatment.89, 90 Co-morbidities are a major determinant of clinical presentation, outcomes, and treatment of patients with HF.91, 92 Ageing of the patient population has led to their increased prevalence in the last years.6, 9 They seem more important in HFpEF and HFmrEF, whereas HFrEF patients have more often CAD as the main cause of HF.23, 24, 93 Co-morbidities are usually divided into cardiovascular, such as hypertension,94 CAD,95 atrial fibrillation,96 stroke,97 and non-cardiovascular, such as cancer,98, 99 chronic renal dysfunction,79, 100 obstructive lung disease,101-103 sleep apnoea,104, 105 iron deficiency,106, 107 anaemia,108-110 sarcopenia,111, 112 anorexia,39, 113 frailty,38, 114 cachexia,115, 116 liver dysfunction,117diabetes mellitus,84, 118 obesity,34, 119, 120 and psychiatric disorders.121 They are often associated with an increased risk of HF in initially asymptomatic patients as they may cause or favour the development of cardiac dysfunction. Second, they cause more severe symptoms and are associated with an increased rate of major events, including cardiovascular and all-cause hospitalizations, and death, once they occur in patients with HF. Their effect may be direct or through a negative impact on the administration of evidence-based treatment, such as is the case of renal dysfunction, which may contraindicate inhibitors of the renin–angiotensin–aldosterone system.91 Their extensive assessment goes beyond the aims of this article. They are considered in the paragraphs about diagnosis and treatment. Control of risk factors for CAD remains the mainstay for prevention of development of HF. Other general measures, such as pneumococcal vaccination, may be important, especially in elderly subject.122 The ESC guidelines have included, for the first time, antidiabetic treatment for the prevention of HF. Namely, empagliflozin, a sodium glucose transporter (SGLT-2) inhibitor, has reduced HF related events and mortality in patients with diabetes at high risk of cardiovascular events, and it is now recommended for HF prevention.2, 123, 124 In contrast, the glucagon-like peptide-1 analogue liraglutide, despite its beneficial effects on stroke, myocardial infarction, and mortality in diabetic patients,125 did not improve LV systolic function and had no effects on cardiac events or increased them, numerically, in two prospective placebo-controlled randomized trials in stable chronic HFrEF patients with and without diabetes.126, 127 Among the dipeptidyl peptidase-4 inhibitors, saxagliptin was associated with an increase in HF hospitalization, whereas alogliptin and sitagliptin were not. No effect on major cardiovascular outcomes was found with all these agents.128-130 Insulin administration was associated with worse outcomes in an analysis of 24 012 patients with HF and diabetes from four large randomized trials and of 103 857 patients from an administrative database. Evidence from prospective studies would be needed.131 No major changes have occurred in current evidence for medical treatment since the results of SHIFT (Systolic HF Treatment with the I(f) Inhibitor Ivabradine Trial) and PARADIGM-HF (A Multicentre, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Patients With Chronic HFrEF).132, 133 The focus is now on the implementation of evidence-based treatment and how much the results of clinical trials can be translated into clinical practice.134, 135 Treatment of HFpEF remains disappointing. It is hypothesized that reduced nitric oxide availability may cause HFpEF so that drugs increasing it may improve these patients.136 However, recent controlled trials with sildenafil as well as with organic nitrates have given neutral results.137-139 Inorganic nitrites have improved arterial compliance, exercise haemodynamics, and exercise capacity in small studies.140-142 The larger INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF) trial has been designed, though with neutral results, as recently presented by Borlaug at the American College of Cardiology (ACC) 2018 Annual Scientific Sessions (unpublished data).143 Slowing heart rate is another potential target of HFpEF treatment. However, in EDIFY (prEserveD LVEF chronic HF with ivabradine studY) (EDIFY), slowing heart rate with ivabradine had no effect on parameters of LV diastolic function and NT-proBNP levels.144 Based on the results of Phase II studies, above all with respect to patient-reported outcomes as endpoints, trials with guanylate cyclase activators are ongoing.145, 146 Results of a major outcome trial with sacubitril/valsartan are expected soon.147 Despite the neutral results with the primary endpoint of TOPCAT, HF hospitalizations were reduced, and geographical differences had a major impact.148 There are, thus, both pathophysiological mechanisms and trial results that suggest that mineralocorticoid receptor antagonists (MRA) should have beneficial effects in HFpEF patients. A trial with a pragmatic study design in HFpEF patients enrolled in a Swedish registry is ongoing.149 Congestion is the main cause of hospitalization for HF patients and diuretics are the mainstay of treatment.2 Diuretic treatment is still based on furosemide administration. Its initial dose and mode of administration, bolus vs. continuous infusion, have not influenced outcomes in a pivotal trial.150 Congestion relief may be monitored by different tools, including clinical signs, imaging methods and laboratory exams.151 A recent prospective study has shown the value of haemoconcentration as a simple but sensitive tool to detect congestion relief and predict post-discharge patients' outcomes.152 Diuretic resistance and, more generally, persistent congestion despite medical treatment is the main limitation to current treatment of AHF. Diuretic resistance is mainly caused by tubular mechanisms rather than insufficient delivery.153 Combination with a thiazide diuretic or metolazone may be effective though with increased rate of worsening renal function and electrolyte abnormalities.154 Other diuretic and aquaretic strategies, such as with the combination of high dose spironolactone or with tolvaptan, have not been effective.155, 156 However, tolvaptan has been associated with favourable outcomes in specific subsets of patients, such as those with diuretic resistance and hyponatraemia, especially in Eastern Asian countries.11, 157, 158 Ultrafi
A 27-year-old woman underwent transthoracic echocardiography for palpitations due to frequent premature ventricular beats, as documented at 24 h electrocardiogram monitoring. Echocardiography showed moderate left and right ventricle (RV) dilatation with good bi-ventricular systolic function; the presence of right coronary sinus dilation was noted (arrow, panel A), and a great spherical sac (3.9 × 4.8 cm) filled with high-velocity swirling Colour Doppler, at the right atrio-ventricular junction (arrow, panel B). This appeared connected through a fistulous tract (panel C, arrow) to the right ventricular inlet. Findings were consistent with giant right coronary artery aneurysm and right ventricular fistula. Panels D–F and Supplementary material online, video SD show 3D angio-CT reconstructions of the aneurysm in its anterior, right lateral, and diaphragmatic aspects, respectively. The proximal right coronary artery (RCA) was tortuous and markedly dilated (up to 24 mm); the aneurysm (An.) reached a maximal diameter of 55 mm, and was connected to the RV inlet with a fistula (Fist.) measuring 25 mm in length and 15 mm in diameter. An acute marginal branch (a.m.b.) originated just above the aneurysm, while two postero-lateral branches originated apparently from it. A subtle posterior inter-ventricular branch originated distally from the aneurysm. Both the anterior descending artery and the circumflex coronary artery were normal in size and morphology.
Abstract Case presentation: In December 2022, A 32–y old women presented to the emergency department of our institution for pain and acrocyanosis of the 3rd and 4th finger of the right hand, compared abruptly 10 hours before. Physical examination was otherwise normal, she was apyretic. Her previous medical history was unremarkable, she did not take any medication and was a light smoker. Blood samples including blood count, platelets, coagulation tests, liver and kidney function, and inflammatory markers were normal. An echocardiogram was prescribed to rule out significant cardiovascular disease. The exam showed: normal left and right ventricular dimensions and systolic function, and absence of significant valvular disease. A highly mobile, iso–echoic mass was noted inside the left ventricle, with a major diameter of 8 mm; it was attached to the antero–lateral papillary muscle, not involving the mitral valve leaflets, and it had a frond–like appearance. Findings were consistent with a fibroelastoma (PFE; figure 1, 2). Doppler examination excluded pathology of ascending aorta, right subclavian artery, and demonstrated patency of arteries of the right arm and right hand. The case was compatible with peripheral embolization from the cardiac mass. A cardiac CT scan confirmed the echo findings and ruled out significant coronary disease. The patient underwent cardiac surgery two days later. With median sternotomy and cardiopulmonary bypass, the left ventricle was reached through aortotomy. A multilobular yellowish mass was seen attached to the antero–lateral papillary muscle, and was completely resected (figure 3); chordae tendineae were preserved. Macroscopic examination (figure 3) and histological findings confirmed the diagnosis of PFE. Post operative course was unremarkable. Discussion PFEs are benign tumors most commonly involving aortic valve, followed by mitral valve; atypical origins including mitral subvalvular apparatus, as in our case, has seldom been described. Most cases of PFE are asymptomatic, limited in dimensions and discovered incidentally. Interestingly, Raynaud phenomenon was at first suspected as cause of acrocyanosis in our patient, but it was inconsistent with biochemical findings, so that an echocardiogram was prescribed. Echo and CT aspects of the mass were typical for PFE, and it appeared at high embolic risk being pedunculated and highly mobile. Given the peripheral ischemic event occurred, prompt surgical resection was performed successfully.
Revisiting blood pressure targets in patients with comorbidities / Remote patient monitoring and telemedicine 855 stand which patients are well-represented and thus reasonable candidates for a SPRINT-supported treatment strategy.Methods: We defined and mapped the "data-rich, data-limited, and data-free zones" of the SPRINT trial based on subjects' baseline characteristics, and not on inclusion and exclusion criteria.For each participant (n=9361), a z-score was computed for 6 distinct continuous variables: age, SBP, fasting serum glucose, non-HDL cholesterol, serum creatinine, and BMI.Individual Summary Scores (SS) were generated based on these parameters-all weighted equally-to scale with the Euclidean distance of the participant from the theoretical "average patient" in six-dimensional space.SS were then calculated for 2007-14 National Health and Nutrition Examination Survey (NHANES) participants' ages 35 years or older, with SBP≥130mmHg, and with HgbA1c<7%.Results: Within SPRINT, a SS of 1.35 represents the 90th percentile and 1.78 represents the 97.5th percentile.We chose these values as borders between the data-rich, data-limited, and data-free zones.Analysis of NHANES participants' SS reveals 17% are in SPRINT's data-limited zone and 8% are in its data-free zone.The NHANES population mapped onto SPRINT data zones shows a landscape of applicability by race and sex (Figure1A.)A decision aid using the six variables, along with the SS, was generated to help clinicians understand how closely a patient approximates the SPRINT trial population.A 47-year-old overweight man with coronary artery disease and normal renal function is within the data-rich zone despite being excluded from SPRINT for age, whereas a 50-year-old prediabetic woman with chronic kidney disease and a BMI of 35 is fully within the SPRINT parameters, yet falls in the data-free zone.A visual aid identifies which parameters are most similar or dissimilar between the patient and the SPRINT population (Figure1B). Conclusion:The process of defining data zones based on patient characteristics holds promise as a refinement in how we judge landmark trials in the context of our patients.
