Left Atrio-ventricular Coupling Index: A Novel Diastolic Parameter to Refine Prognosis in Heart Failure.

BACKGROUND: Left atrioventricular coupling index (LACI), an index coupling left atrial (LA) to left ventricular (LV) volume at end-diastole, showed to be associated with prognosis in different clinical settings. However, the relation between LACI and LV diastolic dysfunction (DD) remains to be established. The present study aimed to investigate the association between LACI and LV DD and to assess its prognostic value in patients with heart failure (HF). METHODS: We retrospectively analyzed 1158 stable HF patients, on optimal medical therapy (derivation cohort). Clinical and echocardiographic features were characterized across LACI tertiles. The independent prognostic value of LACI (endpoint: all-cause death/HF-hospitalization) was assessed by Cox regression. Results were validated in an external cohort of 242 HF patients. RESULTS: In the derivation cohort, the median LACI value was 0.29 (IQR:0.19-0.42). Patients in the third tertile (LACI>0.36) were older and presented with more advanced HF symptoms. While the prevalence of grade-1 DD (ASE/EACVI classification) progressively decreased across LACI tertiles, the prevalence of grade-3 DD significantly increased (8%,23%, and 46% respectively, P<0.0001). A cut-off value ≥0.26 identified moderate-to-severe DD with an area-under the-curve of 0.75. During follow-up (median 28 months, IQR:11-53), 407 (35%) patients reached the endpoint. On multivariable analysis, LACI was independently associated with outcomes (HR for 1-SD increase 1.16; 95%CI 1.06-1.28; P=0.002), showing incremental predictive value over the DD grading system (net reclassification improvement=0.150, P<0.0001). The prognostic value of LACI was consistent in the external validation cohort. CONCLUSIONS: LACI is associated with DD severity and is an independent predictor of outcomes in HF patients.

Left ventricular remodeling response to SGLT2 inhibitors in heart failure: an updated meta-analysis of randomized controlled studies.

BACKGROUND: Randomized controlled trials (RCTs) reported contrasting results about reverse left ventricular remodeling (LVR) after sodium-glucose co-transporter-2 inhibitors (SGLT2i) therapy in patients with heart failure (HF). METHODS AND RESULTS: We performed a metanalysis of RCTs of SGLT2i administration in HF outpatients published until June 2022 searching four electronic databases. The protocol has been published in PROSPERO. Primary LVR outcome was change in absolute LV end-diastolic (LVEDV) and end-systolic volume (LVESV) from baseline to study endpoint. Secondary outcomes included changes in LVEDV and LVESV indexed to body surface area, LV Mass index (LVMi), LV ejection fraction (LVEF), and N-terminal pro-B-type natriuretic peptide (NTproBNP). Mean differences (MDs) with 95% CIs were pooled. A total of 9 RCTs (1385 patients) were analyzed. All of them reported data on LVEF. Six trials reported data on LVESV and LVEDV (n = 951); LVMi was available in 640. SGLT2i treatment significantly reduced LVEDV [MD= -10.59 ml (-17.27; -3.91), P = 0.0019], LVESV [MD= -8.80 ml (-16.91; -0.694), P = 0.0334], and LVMI [MD= -5.34 gr/m2 (-9.76; -0.922), P = 0.0178], while LVEF significantly increased [MD = + 1.98% (0.67; 0.306), P = 0.0031]. By subgroup analysis, the beneficial effects of SGLT2i on LVEF did not differ by imaging method used, time to follow-up re-evaluation, or HF phenotype. Reduction in LV volumes tended to be greater in HF with reduced EF (HFrEF) than in those with preserved EF (HFpEF), while the opposite was observed for LVMi. CONCLUSIONS: Treatment with SGLT2i significantly reversed cardiac volumes, improving LV systolic function and LV mass, particularly in HFrEF patients.

Left Atrial Strain in the Assessment of Diastolic Function in Heart Failure: A Machine Learning Approach.

BACKGROUND: Diastolic dysfunction (DD) assessment in heart failure is still challenging. Peak atrial longitudinal strain (PALS) is strongly related to end-diastolic pressure and prognosis, but it is still not part of standard DD assessment. We tested the hypothesis that a machine learning approach would be useful to include PALS in DD classification and refine prognostic stratification. METHODS: In a derivation cohort of 864 heart failure patients in sinus rhythm (age, 66.6±12 years; heart failure with reduced ejection fraction, n=541; heart failure with mildly reduced ejection fraction, n=129; heart failure with preserved ejection fraction, n=194), machine learning techniques were retrospectively applied to PALS and guideline-recommended diastolic variables. Outcome (death/heart failure rehospitalization) of the identified DD-clusters was compared with that by guidelines-based classification. To identify the best combination of variables able to classify patients in one of the identified DD-clusters, classification and regression tree analysis was applied (with DD-clusters as dependent variable and PALS plus guidelines-recommended diastolic variables as explanatory variables). The algorithm was subsequently validated in a prospective cohort of 189 heart failure outpatients (age, 65±13 years). RESULTS: Three distinct echocardiographic DD-clusters were identified (cluster-1, n=212; cluster-2, n=376; cluster-3 DD, n=276), with modest agreement with guidelines-recommended classification (kappa=0.40; P<0.001). DD-clusters were predicted by a simple algorithm including E/A ratio, left atrial volume index, E/e' ratio, and PALS. After 36.5±29.4 months follow-up, 318 events occurred. Compared to guideline-based classification, DD-clusters showed a better association with events in multivariable models (C-index 0.720 versus 0.733, P=0.033; net reclassification improvement 0.166 [95% CI, 0.035-0.276], P=0.013), without interaction with ejection fraction category. In the validation cohort (median follow-up: 18.5 months), cluster-based classification better predicted outcome than guideline-based classification (C-index 0.80 versus 0.78, P=0.093). CONCLUSIONS: Integrating PALS by machine learning algorithm in DD classification improves risk stratification over recommended current criteria, regardless of ejection fraction status. This proof of concept study needs further validation of the proposed algorithm to assess generalizability to other populations.

Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry.

AIMS: Sacubitril/valsartan has changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects on morbidity and mortality, partly mediated by left ventricular (LV) reverse remodelling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. METHODS AND RESULTS: Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic parameters including LV global longitudinal strain (GLS) and global peak atrial longitudinal strain by speckle tracking echocardiography were measured to find the predictors of LVRR [= LV end-systolic volume reduction ≥10% and ejection fraction (LVEF) improvement ≥10% at follow-up] at 6 month follow-up as the primary endpoint. Changes in symptoms [New York Heart Association (NYHA) class] and neurohormonal activations [N-terminal pro-brain natriuretic peptide (NT-proBNP)] were also evaluated as secondary endpoints; 341 patients (excluding patients with poor acoustic windows and missing data) were analysed (mean age: 65 ± 10 years; 18% female, median LVEF 30% [inter-quartile range: 25-34]). At 6 month follow-up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥ 35%), 55 (16%) early incomplete response (LVRR and LVEF < 35%), and 204 (60%) no response (no LVRR and LVEF < 35%). Non-ischaemic aetiology, a lower left atrial volume index, and a higher GLS were all independent predictors of LVRR at multivariable logistic analysis (all P < 0.01). A baseline GLS < -9.3% was significantly associated with early response (area under the curve 0.75, P < 0.0001). Left atrial strain was the best predictor of positive changes in NYHA class and NT-proBNP (all P < 0.05). CONCLUSIONS: Speckle tracking echocardiography parameters at baseline could be useful to predict LVRR and clinical response to sacubitril-valsartan and could be used as a guide for treatment in patients with HFrEF.

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register.

Aims: This sub-study deriving from a multicentre Italian register [Deformation Imaging by Strain in Chronic Heart Failure Over Sacubitril-Valsartan: A Multicenter Echocardiographic Registry (DISCOVER)-ARNI] investigated whether sacubitril/valsartan in addition to optimal medical therapy (OMT) could reduce the rate of implantable cardioverter-defibrillator (ICD) indications for primary prevention in heart failure with reduced ejection fraction (HFrEF) according to European guidelines indications, and its potential predictors. Methods and results: In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centres were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical, and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Of 351 patients, 225 (64%) were ICD carriers and 126 (36%) were not ICD carriers (of whom 13 had no indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV) ejection fraction (EF) ≤ 35% and New York Heart Association (NYHA) class = II-III, 69 (60%) did not show ICD indications; 44 (40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation > moderate, left atrial volume index (LAVi), and LV global longitudinal strain (GLS) significantly varied between the groups. With receiver operating characteristic curves, age ≥ 75 years, LAVi ≥ 42 mL/m2 and LV GLS ≥-8.3% were associated with ICD indications persistence (area under the curve = 0.65, 0.68, 0.68, respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions: Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/haemorrhagic risks and unnecessary costs deriving from ICDs.

Burden of Ventricular Arrhythmias in Cardiac Resynchronization Therapy Defibrillation and Implantable Cardioverter-Defibrillator Recipients with Recovered Left Ventricular Ejection Fraction: The Additive Role of Speckle-Tracking Echocardiography.

BACKGROUND: Patients with heart failure undergoing cardiac resynchronization therapy with or without defibrillator function may exhibit recovery of left ventricular ejection fraction (LVEF) during follow-up. Mechanical dispersion (MD; the SD of time to peak longitudinal strain by two-dimensional speckle-tracking echocardiography) is a known predictor of life-threatening ventricular arrhythmias (VAs). Relationships among LVEF recovery, changes in MD, and incidence of VA are still not extensively investigated. METHODS: In this retrospective study, recipients of cardiac resynchronization therapy defibrillation (n = 183) or implantable cardioverter-defibrillators only (n = 87) underwent conventional and speckle-tracking echocardiography, both at baseline and after 10 to 12 months, and were followed clinically. Both a ≥10% increase in LVEF and a final LVEF > 35% defined echocardiographic response (EchoResp). Reduction in MD ≥10 msec defined MD response (MDResp). Risk for appropriate implantable cardioverter-defibrillator therapy for VAs was assessed using a multivariable Cox hazard model. RESULTS: The prevalence of EchoResp+ and MDResp+ was 39% and 46%, respectively. During follow-up (49.8 ± 33.5 months), 74 VA events occurred. The incidence rate (per 100 patient-years) of VAs was lowest in the EchoResp+/MDResp+ group (1.66%; 95% CI, 0.69%-3.99%), highest in the EchoResp-/MDResp- group (12.8%; 95% CI, 9.53%-17.2%; P < .0001), and intermediate in the EchoResp-/MDResp+ (5.5%; 95% CI, 3.3%-9.4%) or EchoResp+/MDResp- (5.3%; 95% CI, 3.0%-9.4%) group. Multivariable analysis showed that higher MD at follow-up (>71.4 msec) was associated with VAs independent of whether final LVEF was below or above the guideline-reported cutoff of 35% (P < .05). CONCLUSIONS: Among ICD recipients, improvements in both left ventricular function and MD are associated with reduced risk for VAs. In patients whose follow-up LVEFs improved to >35%, risk for VAs, although substantially decreased, remained elevated in the presence of still elevated MD.

Left atrial structural and mechanical remodelling in heart failure with reduced ejection fraction.

AIMS: In patients with heart failure with reduced ejection fraction (HFrEF), an association between left atrial (LA) dilatation and dysfunction is expected, but the degree of coexistence of the two abnormalities and their relative prognostic role is not known. METHODS AND RESULTS: A total of 626 HFrEF patients formed the study population. All of them underwent a comprehensive echocardiographic evaluation. LA maximal volume was indexed to body surface area (LAVi); LA function was assessed using strain analysis during the reservoir phase: peak atrial longitudinal strain (PALS) analysis. Study primary endpoint was overall mortality or hospitalization for worsening heart failure. Four groups of patients were included in this study according to LAVi (≤34 or >34 mL/m2 ) and PALS (≤23% or >23%); 61 (10%) patients had normal LA volume and function (Group 1), 58 (9%) had LA dilatation but normal function (Group 2), 100 (16%) had normal volume but abnormal function (Group 3), and 407 (65%) had enlarged left atrium and abnormal function (Group 4). PALS was associated with primary endpoint in patients with both normal-size [Groups 1 and 3: hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.88-0.96; P = 0.0006] and dilated left atria (Groups 2 and 4: HR 0.93, 95% CI 0.91-0.96; P < 0.0001). In contrast, LAVi was associated with the primary endpoint in patients with abnormal LA function (Groups 3 and 4: HR 1.018, 95% CI 1.011-1.024; P < 0.00001) but not in those with normal PALS (Groups 1 and 2: HR 1.023, 95% CI 0.99-1.057; P = 0.1). CONCLUSIONS: Left atrial dilatation and dysfunction frequently but not invariably coexist. PALS emerged as a significant prognostic parameter in HFrEF even in the absence of LA dilation.

Global longitudinal strain in heart failure with reduced ejection fraction: Prognostic relevance across disease severity as assessed by automated cluster analysis.

BACKGROUND: Ejection fraction (EF) is still widely used to categorize heart failure (HF) patients but has limitations. Global longitudinal strain (GLS) has emerged as a new prognosticator in HF, independent of EF. AIM: We investigated the incremental predictive benefit of GLS over different risk profiles as identified by automated cluster analysis of simple echocardiographic parameters. METHODS AND RESULTS: In 797 HFrEF patients (age 66 ± 12y; mean EF 30 ± 7%), unsupervised cluster analysis of 10 routine echocardiographic variables (without GLS) was performed. Median follow-up was 37 months. End-point was all-cause mortality. Association between risk profiles, GLS, and mortality was assessed by Cox proportional-hazard modeling with interaction term. Cluster analysis allocated patients to 3 different risk phenogroups (PG): PG-1 (mild diastolic dysfunction [DD], moderate systolic dysfunction, no pulmonary hypertension, normal right ventricular [RV] function); PG-2 (moderate DD, mild pulmonary hypertension, normal RV function); PG-3 (severe DD, advanced systolic dysfunction, pulmonary hypertension, RV dysfunction). Compared to PG-1, PG-2 and PG-3 showed increased adjusted-hazard ratio (1.71; 95% CI:1.05-2.77, P = 0.30; and 2.58; 95% CI:1.50-4.44, P < 0.001, respectively). GLS was independently associated with outcome in the whole population (adjusted-HR: 1.11; 95% CI: 1.05-1.17, P = 0.001); however, profile membership modified the relationship between GLS and outcome which was no longer significant in PG-3 (P for interaction = 0.003). CONCLUSIONS: Within HFrEF populations, clustering of routine echocardiography parameters can automatically identify patients with different risk profiles; further assessment by GLS may be useful for patients with not advanced disease.

Accuracy of ICD-9 codes in identifying patients with peptic ulcer and gastrointestinal hemorrhage in the regional healthcare administrative database of Umbria.

BACKGROUND: Peptic ulcer is a widespread disease, frequently complicated by perforation and bleeding. Administrative databases are useful tool to perform epidemiological and drug utilization studies, but they need a validation process based on a comparison with the original data contained in the medical charts. Our aim was to evaluate the accuracy of the ICD-9 codes in identifying patients with peptic ulcer and gastrointestinal hemorrhage in the regional administrative database of Umbria. METHODS: The index test of our study was the hospital discharge abstract database of the Umbria region (Italy), while the reference standard was the clinical information collected in the medical charts. The study population were adult patients with a hospital discharge for peptic ulcer or gastrointestinal hemorrhage in the period 2012-2014. A random sample of cases and non-cases was selected and the corresponding medical charts were reviewed. Cases of peptic ulcer were confirmed based on endoscopy, radiology, and surgery, while adjudication of gastrointestinal hemorrhage was based on presence of hematemesis, melena, and rectal bleeding. RESULTS: Overall, we reviewed 445 clinical charts of cases and 80 clinical charts of non-cases. The diagnostic accuracy results were: code 531 (gastric ulcer), sensitivity and NPV 98%, specificity 88%, and PPV 91%; code 532 (duodenal ulcer), sensitivity and NPV 100%, specificity and PPV 98%; code 534 (gastrojejunal ulcer), sensitivity and NPV 100%, specificity 70%, and PPV 45%; code 578 (gastrointestinal hemorrhage), sensitivity 96%, specificity 90%, PPV and NPV 94%. CONCLUSIONS: Our results showed a high level of diagnostic accuracy for most of the codes considered. The ICD-9 code 534 of gastrojejunal ulcer had a lower level of specificity and PPV due to false positives, being mainly misclassifications for coding errors. These validated codes can be used for future epidemiological studies and for health services research.

Clinical RoPE (cRoPE) score predicts patent foramen ovale detection among stroke patients: a multicenter observational study.

BACKGROUD: The role of patent foramen ovale (PFO) in cryptogenic stroke (CS) is debated. Tools to predict PFO occurrence and attributable fraction are needed to guide cost-effective diagnostics and treatment. Risk of Paradoxical Embolism (RoPE) score relies on neuroimaging findings, which might be inconclusive in up to 30% of cases. METHODS: We developed a clinical-based easy tool to predict the presence and attributable fraction of PFO in CS patients, without using neuroimaging. The clinical RoPE (cRoPE) score, ranging 1-10, was elaborated through Delphi method from the original RoPE score, replacing cortical infarction with the Oxfordshire Community Stroke Project (OCSP) classification (lacunar stroke = 0 points, other subtypes = 1 point). Then, from the SISIFO (Studio Italiano di prevalenza nello Stroke Ischemico di pervietà del Forame Ovale, or Prevalence of Patent Foramen Ovale in Ischemic Stroke in Italy) study, a multicenter, prospective study on consecutive acute ischemic stroke patients (n = 1130) classified by Trial of Org 10172 in Acute Stroke Treatment (TOAST) and OCSP criteria and undergoing PFO testing, we selected the VV-CDC cohort (Vibo Valentia, Città di Castello, n = 323) to test the accuracy of cRoPE in predicting PFO detection. We compared cRoPE with RoPE to verify cRoPE reliability. Finally, we tested, through ROC analysis, the performance of cRoPE depending on TOAST classification. RESULTS: Overall, PFO was detected in 21% in VV-CDC and in 23.4% in remaining SISIFO cohort (n = 807). cRoPEAUC and RoPEAUC were similar in VV-CDC. cRoPE performance was comparable with RoPE among CS (cRoPEAUC 0.76, 95%CI 0.67-0.85, RoPEAUC 0.75, 95%CI 0.66-0.84). Moving to the remaining SISIFO cohort, cRoPE confirmed satisfactory accuracy in predicting PFO detection in CS patients (cRoPEAUC 0.71, 95%CI 0.66-0.78, p = 0.032). CONCLUSIONS: Conclusions: cRoPE might help in stratification of patients with CS, allowing accurate esteem of the likelihood of PFO to be found, especially in cases when neuroimaging is inconclusive.

Validity of cerebrovascular ICD-9-CM codes in healthcare administrative databases. The Umbria Data-Value Project.

BACKGROUND: Validation of administrative databases for cerebrovascular diseases is crucial for epidemiological, outcome, and health services research. The aim of this study was to validate ICD-9 codes for hemorrhagic or ischemic stroke in administrative databases, to use them for a comprehensive assessment of the burden of disease in terms of major outcomes, such as mortality, hospital readmissions, and use of healthcare resources. METHODS: We considered the hospital discharge abstract database of the Umbria Region (890,000 residents). Source population was represented by patients aged >18 discharged from hospital with a diagnosis of hemorrhagic or ischemic stroke between 2012 and 2014 using ICD-9-CM codes in primary position. We randomly selected and reviewed medical charts of cases and non-cases from hospitals. For case ascertainment we considered symptoms and instrumental tests reported in the medical charts. Diagnostic accuracy measures were computed using 2x2 tables. RESULTS: We reviewed 767 medical charts for cases and 78 charts for non-cases. Diagnostic accuracy measures were: subarachnoid hemorrhage: sensitivity (SE) 100% (95% CI: 97%-100%), specificity (SP) 96% (90-99), positive predictive value (PPV) 98% (93-100), negative predictive value (NPV) 100% (95-100); intracerebral hemorrhage: SE 100% (97-100), SP 98% (91-100), PPV 98% (94-100), NPV 100% (95-100); other and unspecified intracranial hemorrhage: SE 100% (97-100), SP 96% (90-99), PPV 98% (93-100), NPV 100% (95-100); ischemic stroke due to occlusion and stenosis of precerebral arteries: SE 99% (94-100), SP 66 (57-75), PPV 70% (61-77), NPV 99% (93-100); occlusion of cerebral arteries: SE 100% (97-100), SP 87% (78-93), PPV 91% (84-95), NPV 100% (95-100); acute, but ill-defined, cerebrovascular disease: SE 100% (97-100), SP 78% (69-86), PPV % 83 (75-89), NPV 100% (95-100). CONCLUSIONS: Case ascertainment for both ischemic and hemorrhagic stroke showed good or high levels of accuracy within the regional healthcare databases in Umbria. This database can confidently be employed for epidemiological, outcome, and health services research related to any type of stroke.

A diagnostic accuracy study validating cardiovascular ICD-9-CM codes in healthcare administrative databases. The Umbria Data-Value Project.

BACKGROUND: Administrative healthcare databases are useful and inexpensive tools that can provide a comprehensive assessment of the burden of diseases in terms of major outcomes, such as mortality, hospital readmissions, and use of healthcare resources. However, a crucial issue is the reliability of information gathered. The aim of this study was to validate ICD-9 codes for several major cardiovascular conditions, i.e., acute myocardial infarction (AMI), atrial fibrillation/flutter (AF), and heart failure (HF), in order to use them for epidemiological, outcome, and health services research. METHODS: Data from the centralised administrative database of the Umbria Region (890,000 residents, located in Central Italy) were considered. Patients with a first hospital discharge for AMI, AF/flutter, and HF, between 2012 and 2014, were identified using ICD-9-CM codes in primary position. A sample of cases and non-cases was randomly selected, and the corresponding medical charts reviewed by specifically trained investigators. For each disease, case ascertainment was based on all clinical, laboratory, and instrumental examinations available in medical charts. Sensitivity, specificity, and predictive values with 95% confidence intervals (CIs), were calculated. RESULTS: We reviewed 458 medical charts, 128 for AMI, 127 for AF/flutter, 127 for HF, and 76 of non-cases for each condition. Diagnostic accuracy measures of the original discharge diagnosis were as follows. AMI: sensitivity 98% (95% CI, 94-100%), specificity 91% (95% CI, 83-97%), positive predictive value (PPV) 95% (95% CI, 89-98%), negative predictive value (NPV) 97% (95% CI, 91-100%). AF/flutter: sensitivity 95% (95% CI, 90-98%), specificity 95% (95% CI, 87-99%), PPV 97% (95% CI, 92-99%), NPV 92% (95% CI, 84-97%). HF: sensitivity 96% (95% CI, 91-99%), specificity 90% (95% CI, 81-96%), PPV 94% (95% CI, 88-97%), NPV 93% (95% CI, 85-98%). CONCLUSION: The case ascertainment for AMI, AF and flutter, and HF, showed a high level of accuracy (≥ 90%). The healthcare administrative database of the Umbria Region can be confidently used for epidemiological, outcome, and health services research.

Practical considerations on anticoagulation reversal: spotlight on the reversal of dabigatran.

Idarucizumab (Praxbind) is a humanized antibody fragment, that reversibly and with high affinityties up dabigatran (Pradaxa). Anticoagulation reversal is achieved immediately, and with no procoagulant effect. It is administered intravenously and clearance is renal. The main clinical application of idarucizumab is to antagonize bleeding related to dabigatran, especially if it occurs at critical sites, such as nervous system (central or peripheral), intraocular, pericardial, retroperitoneal or pulmonary. Other indications are: i) dabigatran-induced anticoagulation reversal in the need for emergency surgery or procedures at high risk of bleeding; and ii) second-line treatment in bleedings that persist despite local hemostasis procedures. In this narrative review, we comprehensively address clinical indications for idarucizumab, summing up evidence derived from a systematic literature review, but also from case reports.

Superior Prognostic Value of Right Ventricular Free Wall Compared to Global Longitudinal Strain in Patients With Heart Failure.

BACKGROUND: Global right ventricular (RV) longitudinal strain (RVGLS) and free wall RV longitudinal strain (RVFWS) have both been advocated as sensitive tools to evaluate RV function and predict prognosis in patients with heart failure and reduced ejection fraction (HFrEF). However, because the interventricular septum is an integral part of the left ventricle (LV) also, RVGLS might be influenced by LV dysfunction. Thus, we compared the prognostic performance of either RV strain parameter in HFrEF patients, also taking into account the degree of LV systolic dysfunction. METHODS: In 288 prospectively enrolled outpatients with stable HFrEF, RVGLS and RVFWS were assessed by speckle-tracking and LV systolic function by global longitudinal strain and LV ejection fraction. Patients were followed up for 30.2 ± 23.0 months; the primary endpoint was all-cause death/heart failure-related hospitalization. Prognostic performance was assessed by C-statistic and net reclassification improvement. RESULTS: There were 95 events during follow-up. By univariable analysis, both RVGLS (hazard ratio × 1 SD, 1.60; 95% CI, 1.29-1.99; P < .0001) and RVFWS (hazard ratio × 1 SD, 1.82; 95% CI, 1.45-2.29; P < .0001) were associated with outcome, and both remained significant after correction for EMPHASIS risk score, New York Heart Association class, natriuretic peptides, and therapy. However, after further correction for LV systolic function parameters, only RVFWS remained significantly associated with outcome (P < .01). A basic prediction model was improved by adding RVFWS (net reclassification improvement 0.390; P < .05), but not RVGLS. CONCLUSIONS: Although both RVGLS and RVFWS have prognostic value, RVFWS better predicts outcome in HFrEF patients, mainly because it is less influenced by LV longitudinal dysfunction.

Left Atrial Reservoir Function and Outcome in Heart Failure With Reduced Ejection Fraction.

Background Left atrial (LA) volume is a marker of cardiac remodeling and prognosis in heart failure (HF) with reduced ejection fraction (EF), but LA function is rarely measured or characterized. We investigated determinants and prognostic impact of LA reservoir function in patients with HF with reduced EF. Methods and Results In 405 patients with stable HF with reduced EF (EF, ≤40%) in sinus rhythm, we assessed LA reservoir function by both LA total EF (by phasic volume changes) and peak atrial longitudinal strain (PALS; by speckle tracking echocardiography); LA functional index was also calculated. During follow-up (median, 30 months; Q1-Q3, 13-52), 139 patients (34%) reached the composite end point (all-cause death/HF hospitalization). Median PALS was 15.5% (interquartile range, 11.2-20.6). By univariable analysis, all LA function parameters significantly predicted outcome ( P <0.01 for all), with PALS showing the highest predictive accuracy (area under the curve, 0.75; sensitivity, 73%; specificity, 70%). Impaired PALS was associated with greater left ventricular and LA volumes, worse left ventricular EF, left ventricular global longitudinal strain, right ventricular systolic function, and more severe diastolic dysfunction. After multivariable adjustment (including LA volume and left ventricular global longitudinal strain), PALS, but not LA total EF or LA functional index, remained significantly associated with outcome (hazard ratio per 1-SD decrease, 1.38; 95% CI, 1.05-1.84; P=0.030). Adding PALS to a base model, including age, sex, LA volume, EF, E/E' ratio, and global longitudinal strain, provided incremental predictive value (continuous net reclassification improvement, 0.449; P=0.0009). Conclusions In HF with reduced EF, assessment of LA reservoir function by PALS allows powerful prognostication, independently of LA volume and left ventricular longitudinal contraction.

[Hypokinetic cardiac arrest and hypereosinophilia: a case of Kounis or Churg-Strauss syndrome?] / Arresto cardiaco ipocinetico ed ipereosinofilia: sindrome di Kounis o sindrome di Churg-Strauss?

Ischemic heart disease can be caused by multiple factors. However, epidemiological studies have evidenced an association between hypereosinophilia and acute coronary syndrome, most frequently observed in the Kounis and Churg-Strauss syndromes. We here report the case of a 37-year-old man, who was admitted to our hospital for acute coronary syndrome, complicated by hypokinetic cardiac arrest with severe hypereosinophilia.

Prognostic Value of Right Ventricular Dysfunction in Heart Failure With Reduced Ejection Fraction: Superiority of Longitudinal Strain Over Tricuspid Annular Plane Systolic Excursion.

BACKGROUND: In heart failure (HF) with reduced ejection fraction, right ventricular (RV) impairment, as defined by reduced tricuspid annular plane systolic excursion, is a predictor of poor outcome. However, peak longitudinal strain of RV free wall (RVFWS) has been recently proposed as a more accurate and sensitive tool to evaluate RV function. Accordingly, we investigated whether RVFWS could help refine prognosis of patients with HF with reduced ejection fraction in whom tricuspid annular plane systolic excursion is still preserved. METHODS AND RESULTS: A total of 200 patients with HF with reduced ejection fraction (age, 66±11 years; ejection fraction, 30±7%) with preserved tricuspid annular plane systolic excursion (>16 mm) underwent RV function assessment using speckle-tracking echocardiography to measure peak RVFWS. After a median follow-up period of 28 months, 62 (31%) patients reached the primary composite end point of all-cause death/HF rehospitalization. Median RVFWS was -19.3% (interquartile range, -23.3% to -15.0%). By lasso-penalized Cox-hazard model, RVFWS was an independent predictor of outcome, along with Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure-HF score, Echo-HF score, and severe mitral regurgitation. The best cutoff value of RVFWS for prediction of outcome was -15.3% (area under the curve, 0.68; P<0.001; sensitivity, 50%; specificity, 80%). In 50 patients (25%), RVFWS was impaired (ie, ≥-15.3%); event rate (per 100 patients per year) was greater in them than in patients with RVFWS <-15.3% (29.5% [95% confidence interval, 20.4-42.7] versus 9.4% [95% confidence interval, 6.7-13.1]; P<0.001). RVFWS yielded a significant net reclassification improvement (0.584 at 3 years; P<0.001), with 68% of nonevents correctly reclassified. CONCLUSIONS: In patients with HF with reduced ejection fraction with preserved tricuspid annular plane systolic excursion, RV free-wall strain provides incremental prognostic information and improved risk stratification.

Non-cardiac factors for prediction of response to cardiac resynchronization therapy: The value of baseline, and of serial changes, in red cell distribution width.

BACKGROUND: Increased red blood cell distribution width (RDW) has been associated with poor outcome after cardiac resynchronization therapy (CRT). However, whether baseline RDW, and its serial changes after CRT implant, have incremental prognostic value is unknown. METHODS AND RESULTS: In 148 consecutive patients (age, 68±9years; 122 men) undergoing CRT, RDW was assessed before and 3months after implant. Patients were categorized according to baseline RDW (≤14.5% vs >14.5%); and as "stable", "decreased", "increased", relative to post-implant changes. Primary end-point was a composite of death/HF hospitalization during follow-up (median 21months). A reduction in left ventricular (LV) end-systolic volume by ≥15% at 6-month identified LV reverse remodeling. By multivariable logistic regression analysis "increased" (OR:0.22, 95%CI: 0.07-0.69, P=0.010) and "stable-high" RDW at follow-up (OR: 0.39, 95%CI: 0.17-0.89, P=0.027) showed a lower likelihood to develop LV reverse remodeling, while baseline RDW was no longer predictive of LV remodeling. During follow-up, there were 57 events. Baseline RDW>14.5% (HR: 2.24, 95%CI: 1.05-4.77, P=0.036), "increased" (HR: 2.55, 95% CI: 1.09-5.97, P=0.030) and "stable-high" RDW (HR: 2.95, 95% CI: 1.45-5.99, P=0.003) independently predicted outcome after adjusting for functional improvement after CRT, radial dyssynchrony, BNP, creatinine clearance, and left atrial volume index. However, integrated discrimination improvement and net reclassification improvement were not statistically significant when both baseline RDW and its changes were added to a base predictive model. CONCLUSION: Increased and stable-high values of RDW were independently associated with both LV reverse remodeling and outcome after CRT; however, RDW did not show any incremental predictive value.

Protocol for validating cardiovascular and cerebrovascular ICD-9-CM codes in healthcare administrative databases: the Umbria Data Value Project.

INTRODUCTION: Administrative healthcare databases can provide a comprehensive assessment of the burden of diseases in terms of major outcomes, such as mortality, hospital readmissions and use of healthcare resources, thus providing answers to a wide spectrum of research questions. However, a crucial issue is the reliability of information gathered. Aim of this protocol is to validate International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) codes for major cardiovascular diseases, including acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF) and stroke. METHODS AND ANALYSIS: Data from the centralised administrative database of the entire Umbria Region (910 000 residents, located in Central Italy) will be considered. Patients with a first hospital discharge for AMI, HF, AF or stroke, between 2012 and 2014, will be identified in the administrative database using the following groups of ICD-9-CM codes located in primary position: (1) 410.x for AMI; (2) 427.31 for AF; (3) 428 for HF; (4) 433.x1, 434 (excluding 434.x0), 436 for ischaemic stroke, 430 and 431 for haemorrhagic stroke (subarachnoid haemorrhage and intracerebral haemorrhage). A random sample of cases, and of non-cases, will be selected, and the corresponding medical charts retrieved and reviewed for validation by pairs of trained, independent reviewers. For each condition considered, case adjudication of disease will be based on symptoms, laboratory and diagnostic tests, as available in medical charts. Divergences will be resolved by consensus. Sensitivity and specificity with 95% CIs will be calculated. ETHICS AND DISSEMINATION: Research protocol has been granted approval by the Regional Ethics Committee. Study results will be disseminated widely through peer-reviewed publications and presentations at national and international conferences.