A machine learning-based lung ultrasound algorithm for the diagnosis of acute heart failure.

Lung ultrasound (LUS) is an effective tool for diagnosing acute heart failure (AHF). However, several imaging protocols currently exist and how to best use LUS remains undefined. We aimed at developing a lung ultrasound-based model for AHF diagnosis using machine learning. Random forest and decision trees were generated using the LUS data (via an 8-zone scanning protocol) in patients with acute dyspnea admitted to the Emergency Department (PLUME study, N = 117) and subsequently validated in an external dataset (80 controls from the REMI study, 50 cases from the Nancy AHF cohort). Using the random forest model, total B-line sum (i.e., in both hemithoraces) was the most significant variable for identifying AHF, followed by the difference in B-line sum between the superior and inferior lung areas. The decision tree algorithm had a good diagnostic accuracy [area under the curve (AUC) = 0.865] and identified three risk groups (i.e., low 24%, high 70%, and very high-risk 96%) for AHF. The very high-risk group was defined by the presence of 14 or more B-lines in both hemithoraces while the high-risk group was described as having either B-lines mostly localized in superior points or in the right hemithorax. Accuracy in the validation cohort was excellent (AUC = 0.906). Importantly, adding the algorithm on top of a validated clinical score and classical definition of positive LUS scanning for AHF resulted in a significant improvement in diagnostic accuracy (continuous net reclassification improvement = 1.21, P < 0.001). Our simple lung ultrasound-based machine learning algorithm features an excellent performance and may constitute a validated strategy to diagnose AHF.

Prognostic implication of lung ultrasound in heart failure: pooled analysis of international cohorts.

BACKGROUND: Lung ultrasound (LUS) is often used to assess congestion in heart failure (HF). In this study, we assessed the prognostic role of LUS in HF patients at admission and hospital discharge, and in an out-patient setting and explored whether clinical factors (age, sex, left ventricular ejection fraction (LVEF) and atrial fibrillation) impact the prognostic value of LUS findings. Further, we assessed the incremental prognostic value of LUS on top of AHEAD and MAGGIC clinical risk scores. METHODS AND RESULTS: We pooled data of patients hospitalized for HF or followed-up in out-patient clinics from international cohorts. We enrolled 1,947 patients, at admission (n=578), discharge (n=389) and in out-patient clinic (n=980). Total LUS B-line count was calculated for the 8-zone scanning protocol. The primary outcome was a composite of re-hospitalization for HF and all-cause death. Compared to those in the lower tertiles of B-lines, patients in the highest tertile were older, more likely to have signs of HF and higher NT-proBNP levels. A higher number of B-lines was associated with increased risk of primary outcome at discharge (Tertile3 vs Tertile1: adjustedHR= 5.74 (3.26- 10.12), p<0.0001) and in out-patients (Tertile3 vs Tertile1: adjustedHR= 2.66 (1.08- 6.54), p=0.033). Age and LVEF did not influence the prognostic capacity of LUS in different clinical settings. Adding B-line count to MAGGIC and AHEAD scores improved net reclassification significantly in all three clinical settings. CONCLUSION: A higher number of B-lines in patients with HF was associated with increased risk of morbidity and mortality, regardless of the clinical setting.

[Non-inferiority trials]. / Gli studi di non-inferiorità.

Superiority trials are designed to test the hypothesis that a given diagnostic or therapeutic strategy is better than (i.e. "superior to") placebo or an active control. Conversely, non-inferiority trials test the hypothesis that a newer (i.e. alternative) strategy is not "unacceptably worse" than a control (i.e. "traditional", or "older") strategy. Non-inferiority trials are increasingly conducted in clinical medicine more often when a "newer" strategy is supposed to offer a relevant advantage in terms other than clinical efficacy (i.e. better tolerability, less cost, simpler regimen, etc.) versus a "gold standard" traditional strategy. The principle underlying non-inferiority trials is that the above advantage justifies the preferential use of the newer strategy in the clinical practice even if the clinical efficacy of the "new" appears to be a bit worse than that of the "old", albeit not unacceptably worse (i.e. not beyond a pre-specified value). The demonstration of non-inferiority requires that the confidence interval of the point estimate (e.g. the hazard ratio) does not cross a pre-specified limit. The definition of such pre-specified limit, the so called "non-inferiority margin", is a pivotal point when planning non-inferiority trials. It denotes the maximally tolerated worse effect of the alternative strategy, compared with the traditional one, required to conclude that an alternative strategy is non-inferior to the traditional "gold standard". The non-inferiority margin is derived from previous trials evaluating the efficacy of the traditional strategy vs placebo. We reviewed the principles and the practical aspects in the design and conduct of non-inferiority trials.

Multi-modality assessment of congestion in acute heart failure: Associations with left ventricular ejection fraction and prognosis.

BACKGROUND: Integrating clinical examination with ultrasound measures of congestion could improve risk stratification in patients hospitalized with acute heart failure (AHF). AIM: To investigate the prevalence of clinical, echocardiographic and lung ultrasound (LUS) signs of congestion according to left ventricular ejection fraction (LVEF) and their association with prognosis in patients with AHF. METHODS: We pooled the data of four cohorts of patients (N = 601, 74.9±10.8 years, 59 % men) with AHF and analysed six features of congestion at enrolment: clinical (peripheral oedema and respiratory rales), biochemical (BNP/NT-proBNP≥median), echocardiographic (inferior vena cava (IVC)≥21 mm, pulmonary artery systolic pressure (PASP)≥40 mmHg, E/e'≥15) and B-lines ≥25 (8-zones) in those with reduced (<40 %, HFrEF), mildly reduced (40-49 %, HFmrEF and preserved (≥50 %HFpEF) LVEF. RESULTS: Compared to patients with HFmrEF (n = 110) and HFpEF (n = 201), those with HFrEF (N = 290) had higher natriuretic peptides, but prevalence of clinical (39 %), echocardiographic (IVC≥21 mm: 56 %, E/e'≥15: 57 %, PASP≥40 mmHg: 76 %) and LUS (48 %) signs of congestion was similar. In multivariable analysis, clinical (HR: 3.24(2.15-4.86), p < 0.001), echocardiographic [(IVC≥21 mm (HR:1.91, 1.21-3.03, p=0.006); E/e'≥15 (HR:1.54, 1.04-2.28, p = 0.031)] and LUS (HR:2.08, 1.34-3.24, p = 0.001) signs of congestion were significantly associated with all-cause mortality and/or HF re-hospitalization. Adding echocardiographic and LUS features of congestion to a model than included age, sex, systolic blood pressure, clinical congestion and natriuretic peptides, improved prediction at 90 and 180 days. CONCLUSIONS: Clinical and ultrasound signs of congestion are highly prevalent in patients with AHF, regardless of LVEF and their combined assessment improves risk stratification.

Hypotension in heart failure is less harmful if associated with high or increasing doses of heart failure medication: Insights from the Swedish Heart Failure Registry.

AIMS: Heart failure (HF) medication may reduce blood pressure (BP). Low BP is associated with worse outcomes but how this association is modified by HF medication has not been studied. We evaluated the association between BP and outcomes according to HF medication dose in HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We studied HFrEF patients from the Swedish HF registry (2000-2018). Associations between systolic BP (SBP) and cardiovascular death (CVD) and/or HF hospitalization (HFH) were analysed according to doses of renin-angiotensin system (RAS) inhibitors, beta-blockers and mineralocorticoid receptor antagonists (MRA). Among 42 040 patients (median age 74.0), lower baseline SBP was associated with higher risk of CVD/HFH (adjusted hazard ratio [HR] per 10 mmHg higher SBP: 0.92, 95% confidence interval [CI] 0.92-0.93), which was less high risk under optimized RAS inhibitor and beta-blocker doses (10% decrease in event rates per 10 mmHg SBP increase in untreated patients vs. 7% decrease in patients at maximum dose, both adjusted p < 0.02). Among the 13 761 patients with repeated measurements, 9.9% reported a SBP decrease >10 mmHg when HF medication doses were increased, whereas 24.6% reported a SBP decrease >10 mmHg with stable/decreasing doses. Decreasing SBP was associated with higher risk of CVD/HFH in patients with stable (HR 1.10, 95% CI 1.04-1.17) or decreasing (HR 1.29, 95% CI 1.18-1.42) HF medication dose but not in patients with an increase in doses (HR 0.94, 95% CI 0.86-1.02). CONCLUSIONS: The association of lower SBP with higher risk of CVD/HFH is attenuated in patients with optimized HF medication. These results suggest that low or declining SBP should not limit HF medication optimization.

Interpretation of Ambulatory Blood Pressure Monitoring for Risk Stratification in Hypertensive Patients: The 'Ambulatory Does Prediction Valid (ADPV)' Approach.

Several outcome-based prospective investigations have provided solid data which support the prognostic value of 24 h ambulatory blood pressure over and beyond cardiovascular traditional risk factors. Average 24 h, daytime, and nighttime blood pressures are the principal components of the ambulatory blood pressure profile that have improved cardiovascular risk stratification beyond traditional risk factors. Furthermore, several additional ambulatory blood pressure measures have been investigated. The correct interpretation in clinical practice of ambulatory blood pressure monitoring needs a standardization of methods. Several algorithms for its clinical use have been proposed. Implementation of the results of ambulatory blood pressure monitoring in the management of individual subjects with the aim of improving risk stratification is challenging. We suggest that clinicians should focus attention on ambulatory blood pressure components which have been proven to act as the main independent predictors of outcome (average 24 h, daytime, and nighttime blood pressure, pulse pressure, dipping status, BP variability).

Exercise-induced B-lines for the diagnosis of heart failure with preserved ejection fraction: a two-centre study.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging despite the use of scores/algorithms. This study intended to assess the diagnostic value of exercise lung ultrasound (LUS) for HFpEF diagnosis. METHODS: We studied two independent case-control studies of HFpEF patients and control subjects undergoing different exercise protocols: (i) submaximal exercise stress echocardiography (ESE) with LUS performed by expert cardiologists (N = 116, HFpEF = 65.5%), and (ii) maximal cycle ergometer test (CET) (N = 54, HFpEF = 50%) with LUS performed by unexperienced physicians shortly trained for the study. B-line kinetics (i.e. peak values and their changes from rest) were assessed. RESULTS: In the ESE cohort, the C-index (95% CI) of peak B-lines for HFpEF diagnosis was 0.985 (0.968-1.000), whereas the C-index of rest and exercise HFA-PEFF scores (i.e. including stress echo findings) were < 0.90 (CI 0.823-0.949), and that of H2FPEF score was < 0.70 (CI 0.558-0.764). The C-index increase of peak B-lines on top of the above-mentioned scores was significant (C-index increase > 0.090 and P-value < 0.001 for all). Similar results were observed for change B-lines. Peak B-lines > 5 (sensitivity = 93.4%, specificity = 97.5%) and change B-lines > 3 (sensitivity = 94.7%, specificity = 87.5%) were the best cutoffs for HFpEF diagnosis. Adding peak or change B-lines on top of HFpEF scores and BNP significantly improved diagnostic accuracy. Peak B-lines showed a good diagnostic accuracy in the LUS beginner-led CET cohort (C-index = 0.713, 0.588-0.838). CONCLUSIONS: Exercise LUS showed excellent diagnostic value for HFpEF diagnosis regardless of different exercise protocols/level of expertise, with additive diagnostic accuracy on top of available scores and natriuretic peptides.

Therapy of Type 2 diabetes: more gliflozines and less metformin?

Metformin is a frequently used anti-diabetic drug. In addition to the well-known modulating properties on glyco-metabolic control, metformin reduces cardiovascular (CV) risk partly independently of its anti-hyperglycaemic effect. The use of 'new' anti-diabetic drugs, inhibitors of the renal Na-glucose co-transporter (SGLTs-I or 'gliflozines') and GLP-1 receptor agonists (GLP1-RAs), has further contributed to challenge the strictly 'gluco-centric' view of diabetic CV disease. Several controlled trials have demonstrated that the cardio-renal benefits of gliflozines and GLP1-RAs are present regardless of the presence of metformin as 'background' therapy. The impact on the 'cardio-renal continuum' exerted by SGLTs-I was also noted in non-diabetic patients with heart failure and reduced or preserved ventricular function and different levels of renal function. These drugs reduced re-hospitalization, CV mortality, and progression to end-stage renal disease. These clinical acquisitions, implemented by Scientific Societies, have led to a change in the therapeutic approach to diabetic cardio-renal disease. Although metformin still represents a valid therapeutic option to be offered particularly to 'naïve' diabetic patients without previous cardio-renal events, SGLTs-I and/or GLP1-RAs emerge as 'first-line' drugs in diabetic patients with previous CV events, or at high CV risk, without having to request 'on board' metformin therapy.

Rationale and design of the Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure: BEGIN-HF study.

AIMS: Sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) represent a unique class of anti-hyperglycaemic agents for type 2 diabetes mellitus that selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT-2i in patients with heart failure (HF), unrelated to its glucosuric effect. It is unclear whether the benefits of SGLT-2i therapy also rely on the improvement of left ventricular (LV) and/or right ventricular (RV) function in patients with HF. This study aimed to evaluate the effect of SGLT-2i on LV and RV function through conventional and advanced echocardiographic parameters with a special focus on RV function in patients with HF. METHODS AND RESULTS: The Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure (BEGIN-HF) study is an international multicentre, prospective study that will evaluate the effect of SGLT-2i on echocardiographic parameters of myocardial function in patients with chronic stable HF across the left ventricular ejection fraction (LVEF) spectrum. Patients with New York Heart Association Class II/III symptoms, estimated glomerular filtration rate > 25 mL/min/1.73 m2 , age > 18 years, and those who were not previously treated with SGLT-2i will be included. All patients will undergo conventional, tissue-derived imaging (TDI), and strain echocardiography in an ambulatory setting, at time of enrolment and after 6 months of SGLT-2i therapy. The primary endpoint is the change in LV function as assessed by conventional, TDI, and myocardial deformation speckle tracking parameters. Secondary outcomes include changes in RV and left atrial function as assessed by conventional and deformation speckle tracking echocardiography. Univariate and multivariate analyses will be performed to identify predictors associated with primary and secondary endpoints. CONCLUSIONS: The BEGIN-HF will determine whether SGLT-2i therapy improves LV and/or RV function by conventional and advanced echocardiography in patients with HF irrespective of LVEF.

Validation of the MEDIA echo score for the prognosis of heart failure with preserved ejection fraction.

There is currently no widely used prognostic score in heart failure (HF) with preserved ejection fraction (HFpEF). The MEDIA echo score, including four variables (pulmonary arterial systolic pressure > 40 mmHg, inferior vena cava collapsibility index < 50%, average E/e' > 9, and lateral mitral annular s' < 7 cm/s), has been proposed as a useful risk stratification tool. This study aimed at further validating the MEDIA echo score in both hospitalised and ambulatory HFpEF patients. The MEDIA echo score ranges from 0 to 4 (each criterion scores 1 point). The associations between MEDIA echo score and cardiovascular outcomes were assessed in two independent HFpEF cohorts, namely patients hospitalised for worsening HFpEF (N = 242, mean age 78 ± 11), and stable ambulatory HFpEF patients (N = 76, mean age 65 ± 8). Using multivariable Cox models, in the worsening HFpEF cohort, patients with a MEDIA echo score of 3-4 displayed a significant increased risk of death (HR 2.10, 95%CI 1.02-4.33, P = 0.043, score 0-1 as reference). In the ambulatory HFpEF cohort, patients with a MEDIA echo score of 2 had a significantly higher risk of death or HF hospitalisation (HR 3.44, 95%CI 1.27-9.30, P = 0.015, score 0 as reference), driven by HF hospitalisation; in that cohort, adding the MEDIA echo score to the clinical model significantly improved reclassification for the combined endpoint (integrated discrimination improvement 6.2%, P = 0.006). The MEDIA echo score significantly predicted the outcome of HFpEF patients in both hospital and ambulatory settings; its use may help refine routine risk stratification on top of well-established prognosticators in stable HFpEF patients.

A Rare Case of Isolated Right Ventricular Loeffler's Endocarditis in Primary Hypereosinophilic Syndrome.

Hypereosinophilic syndrome (HES) is a systemic disorder with various manifestations, characterized by hypereosinophilia and caused by primary or secondary conditions. Loeffler's endocarditis (LE) represents a frequent cardiac manifestation of HES, caused by infiltration of the myocardium by eosinophilic cells, which determines endocardial damage, with subsequent inflammation, thrombosis, and fibrosis of either one or both ventricles. The diagnosis of cardiac involvement is based on a multimodality approach (i.e., two-dimensional transthoracic echocardiography [2D-TTE], speckle-tracking echocardiography [STE], and cardiac magnetic resonance [CMR]), with different findings depending on the stage of disease. STE may be useful in the initial phase when traditional imaging techniques may result negative, whereas CMR allows myocardial tissue characterization along with a better definition of the right ventricle. We present a rare case of LE with isolated right ventricular involvement in a patient with HES caused by chronic eosinophilic leukemia with constitutively activated fusion tyrosine kinase on chromosome 4q12, successfully treated with imatinib mesylate.

Cardiac complications of COVID-19 vaccination: now we know more.

The proliferation of good quality observational studies on the potential adverse effects of COVID-19 vaccination has greatly increased our knowledge on myocarditis and pericarditis, and also, more recently, on arterial hypertension. According to some recent studies, the incidence of a significant increase in blood pressure after COVID-19 vaccination is about 3.2% (95% CI: 1.62-6.21). The incidence of serious hypertensive emergencies or stage III hypertension has been reported as 0.6%. It is well known that the 'spike protein' of the Sars-CoV-2 virus, the synthesis of which is induced by vaccines, binds to ACE2 receptors, inducing their migration towards the inside of the cell. This would result in a lack of ACE2 activity on cell surfaces and therefore a relative deficiency of angiotensin1-7 with a relative excess of angiotensin II, which could explain, at least in part, the blood pressure increases. Regarding myo-pericarditis, there is evidence that the advantages of COVID-19 vaccination over non-vaccination remain preponderant in terms of prevented hospitalizations and serious complications of COVID-19, compared with the risk of developing myocarditis. In the age group most at risk of COVID-19 vaccine myocarditis (12-29 years), for every 100 000 vaccinated, compared to about four more cases of myocarditis we have 56 fewer hospitalizations, 13.8 admissions to intensive care and 0.6 fewer deaths. Several studies have shown that post vaccine myocarditis/pericarditis are generally short-lasting phenomena with favourable clinically course.

Nonbacterial Thrombotic Endocarditis with Multiple Systemic Emboli in a Patient with Primary Lung Cancer.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition that refers to a spectrum of noninfectious lesions of cardiac valves that is most commonly seen in advanced malignancy. We describe a case report of a 63-year-old male with NBTE and multiple embolizations (encephalic, coronary, splenic, and renal). The patient was admitted to the emergency department for stroke. During hospitalization, the patient complained of left leg pain and a venous echo color Doppler of the lower limbs was performed, showing bilateral distal deep-vein thrombosis. A thoracoabdominal computed tomography scan, which was performed to rule out pulmonary embolism, revealed a primary lung cancer and subcarinal lymphadenopathy. As collateral findings, multiple ischemic lesions in the spleen and in both kidneys were identified. In addition, areas of subendocardial hypodensity compatible with ischemia were also highlighted. An electrocardiogram showed acute myocardial infarction and focused echocardiographic evaluation displayed hypokinesis of the lateral and posterior in the mid- and distal segments and aortic and mitral valve vegetations, confirmed by a transesophageal echocardiography. Empiric antimicrobial therapy was started; all blood culture sets were negative and the patient was apyretic throughout the hospitalization. These findings supported the hypothesis of NBTE with multiple embolizations during a hypercoagulable state associated with advanced lung cancer.

Paradigm shift in heart failure treatment: are cardiologists ready to use gliflozins?

Despite recent advances in chronic heart failure (HF) therapy, the prognosis of HF patients remains poor, with high rates of HF rehospitalizations and death in the early months after discharge. This emphasizes the need for incorporating novel HF drugs, beyond the current approach (that of modulating the neurohumoral response). Recently, new antidiabetic oral medications (sodium-glucose cotransporter 2 inhibitors (SGLT2i)) have been shown to improve prognosis in diabetic patients with previous cardiovascular (CV) events or high CV risk profile. Data from DAPA-HF study showed that dapaglifozin is associated with a significant reduction in mortality and HF hospitalization as compared with placebo regardless of diabetes status. Recently, results from EMPEROR-Reduced HF trial were consistent with DAPA-HF trial findings, showing significant beneficial effect associated with empagliflozin use in a high-risk HF population with markedly reduced ejection fraction. Results from the HF with preserved ejection fraction trials using these same agents are eagerly awaited. This review summarizes the evidence for the use of gliflozins in HF treatment.

Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.

OBJECTIVES: CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting. METHODS: We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of new ACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64 ± 11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458). RESULTS: During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80 ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p<0.0001), 1.10 (95% CI: 1.02 to 1.19, p=0.010), and 1.00 (95% CI: 0.86 to 1.16, p=0.983), respectively. In multivariable Cox regression models with adjustment for several potential confounders including age, acute or chronic coronary syndrome, multi-vessel disease, stent placement, diabetes, previous coronary events and dyslipidemia, sCD40L remained an independent predictor of ACS and coronary restenosis. There were no interactions between sCD40L and acute or chronic coronary syndrome or stent placement. CONCLUSIONS: Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.

Certainties fading away: ß-blockers do not worsen chronic obstructive pulmonary disease.

For many years, ß-blockers have been considered contraindicated in patients with heart failure (HF) and in those with bronchial asthma or even chronic obstructive pulmonary disease (COPD) although without clear evidence of asthma. Today, despite overwhelming evidence of the usefulness of ß-blockers, especially in HF with reduced left ventricular ejection fraction (HFrEF), and in ischaemic heart disease, some reluctance persists in using these drugs when COPD coexists. Such resistance is due to the fear that a possible worsening of bronchospasm induced by ß-blockers could induce negative effects greater than the benefits. The Guidelines of the European Society of Cardiology clearly suggest that: (i) implantation of a cardiac defibrillator (ICD) are not contraindicated in COPD without clear evidence of bronchial asthma; (ii) ß-blockers are only 'relatively' contraindicated when there is certainty of bronchial asthma with a documented bronchodilator response to the ß2 stimulant. Therefore, bronchial asthma is not an absolute contraindication to ß-blockers. The cardiologist should not limit the diagnosis of COPD to clinical suspicion, but should rely on a spirometry examination associated with any bronchodilation tests. In any case, selective ß1 blockers are preferred, starting at a basic dose, which ensure a better dilator response to bronchodilators and in any case cause less bronchospasm than non-selective ß-blockers. Unfortunately, there is still some reluctance to the use of ß-blockers in patients with COPD associated with HF, which should be eliminated.

Exercise-induced B-lines in heart failure with preserved ejection fraction occur along with diastolic function worsening.

AIMS: Pulmonary congestion during exercise assessed by lung ultrasound predicts negative outcome in patients with heart failure with preserved ejection fraction (HFpEF). We aimed at assessing predictors of exercise-induced pulmonary B-lines in HFpEF patients. METHODS AND RESULTS: Eighty-one I-II NYHA class HFpEF patients (65.0  ± 8.2 y/o, 56.8% females) underwent standard and strain echocardiography, lung ultrasound, and natriuretic peptide assessment during supine exercise echocardiography (baseline and peak exercise). Peak values and their changes were compared in subgroups according to exercise lung congestion grading (peak B-lines >10 or ≤10). Exercise elicited significant changes for all echocardiographic parameters in both subgroups [39/81 (48.1%) with peak B-lines >10; 42/81 (51.9%) with B-lines ≤10]. Peak values and changes of E-wave (and its derived indices) were significantly higher in patients with >10 peak B-lines compared with those with ≤10 B-line (all P-values <0.03), showing significant correlation with peak B-lines for all parameters; concomitantly, global longitudinal strain (GLS) and global strain rate (GSR) during systole (GSRs), early (GSRe) and late (GSRa) diastole, and isovolumic relaxation (GSRivr) were reduced in patients with B-lines >10 (all P-values <0.05), showing a negative correlation with peak B-lines. By adjusted linear regression analysis, peak and change diastolic parameters (E-wave, E/e', GSRivr, and E/GSRivr) and peak GLS were individually significantly associated with peak B-lines. By covariate-adjusted multivariable model, E/e' and GSRa at peak exercise were retained as independent predictors of peak B-lines, with substantial goodness of fit of model (adjusted R2 0.776). CONCLUSIONS: In HFpEF, development of pulmonary congestion upon exercise is mostly concomitant with exercise-induced worsening of diastolic function.

Acute Myocarditis Associated with Legionella Infection: Usefulness of Layer-specific Two-dimensional Longitudinal Speckle-tracking Analysis.

Pneumonia is the most commonly described manifestation of Legionella pneumophila infection (legionellosis), and extrapulmonary manifestations are uncommon. There are a few descriptions of acute myocarditis associated with legionellosis. We present a case of acute myocarditis in a patient admitted for legionellosis with multisystemic involvement (lung, heart, and kidney). Left ventricular (LV) dysfunction was documented by cardiac magnetic resonance (CMR) and two-dimensional speckle-tracking echocardiography; layer-specific strain analyses were performed, which allowed to differentiate subendocardial or subepicardial contractile impairment. Layer-specific strain analyses by echocardiography demonstrated impairment of subepicardial deformation in the inferolateral wall, which mirrored CMR findings, showing late gadolinium enhancement in the subepicardium of the same LV segments. After initiation of appropriate antibiotic therapy with levofloxacin, LV systolic function rapidly improved as assessed by both CMR and strain analyses, with concomitant normalization of both clinical and biochemical abnormalities. The basic mechanisms of myocardial involvement during legionellosis are unclear; we discussed our findings according to the limited available evidence.