Heart Failure With Mid-range or Recovered Ejection Fraction: Differential Determinants of Transition

The recent definition of an intermediate clinical phenotype of heart failure (HF) based on an ejection fraction (EF) of between 40% and 49%, namely HF with mid-range EF (HFmrEF), has fuelled investigations into the clinical profile and prognosis of this patient group. HFmrEF shares common clinical features with other HF phenotypes, such as a high prevalence of ischaemic aetiology, as in HF with reduced EF (HFrEF), or hypertension and diabetes, as in HF with preserved EF (HFpEF), and benefits from the cornerstone drugs indicated for HFrEF. Among the HF phenotypes, HFmrEF is characterised by the highest rate of transition to either recovery or worsening of the severe systolic dysfunction profile that is the target of disease-modifying therapies, with opposite prognostic implications. This article focuses on the epidemiology, clinical characteristics and therapeutic approaches for HFmrEF, and discusses the major determinants of transition to HFpEF or HFrEF

Left atrial appendage occlusion in the absence of intraprocedural product specialist monitoring: is it time to proceed alone? Results from a multicenter real-world experience

BackgroundPercutaneous left atrial appendage occlusion (LAAO) presents many technical complex features, and it is often performed under the intraprocedural surveillance of a product specialist (PS). Our aim is to assess whether LAAO is equally safe and effective when performed in high-volume centers without PS support.MethodsIntraprocedural results and long-term outcome were retrospectively assessed in 247 patients who underwent LAAO without intraprocedural PS monitoring between January 2013 and January 2022 at three different hospitals. This cohort was then matched to a population who underwent LAAO with PS surveillance. The primary end point was all-cause mortality at 1 year. The secondary end point was a composite of cardiovascular mortality plus nonfatal ischemic stroke occurrence at 1 year.ResultsOf the 247 study patients, procedural success was achieved in 243 patients (98.4%), with only 1 (0.4%) intraprocedural death. After matching, we did not identify any significant difference between the two groups in terms of procedural time (70 ± 19 min vs. 81 ± 30 min, p = 0.106), procedural success (98.4% vs. 96.7%, p = 0.242), and procedure-related ischemic stroke (0.8% vs. 1.2%, p = 0.653). Compared to the matched cohort, a significant higher dosage of contrast was used during procedures without specialist supervision (98 ± 19 vs. 43 ± 21, p < 0.001), but this was not associated with a higher postprocedural acute kidney injury occurrence (0.8% vs. 0.4%, p = 0.56). At 1 year, the primary and the secondary endpoints occurred in 21 (9%) and 11 (4%) of our cohort, respectively. Kaplan–Meier curves showed no significant difference in both primary (p = 0.85) and secondary (p = 0.74) endpoint occurrence according to intraprocedural PS monitoring.ConclusionsOur results show that LAAO, despite the absence of intraprocedural PS monitoring, remains a long-term safe and effective procedure, when performed in high-volume centers

Ambulatory blood pressure monitoring by a novel cuffless device: a pilot study

Purpose Cuffless blood pressure (CL-BP) measurements are believed to be a potentially alternative to cuff-occlusion-based (C-BP) measurement. A new cuffless device was developed for ambulatory BP monitoring. We assessed the accuracy of a new CL-BP device compared to a standard oscillatory C-BP device over the 24 h. Materials and methods Eighty-four consecutive patients were included in the study. BP was measured simultaneously by the CL-BP device and by a C-BP device over the 24 h. Calculations included 24 h mean systolic (S) BP, the mean diastolic (D) BP and the heart rate (HR). Correlations between the CL-BP and C-BP measurements were sought using Pearson’s correlation coefficients and Bland-Altman plots. Results Using the C-BP device, the 24 h SBP value for the cohort was 125.4 ± 10.9 mmHg (mean ± SD); the corresponding DBP value being 75 ± 8.3 mmHg. Mean SBP/DBP were higher with the CL-BP device, i.e. 131.1 ± 15.9/80.2 ± 9.7 mmHg . The correlation coefficients between the two sets of values were significant (SBP: r = 0.58, DBP: r = 0.65). Better correlations for SBP and DBP were found 1) in patients with BMI > 25 (SBP: r = 0.65, DBP: r = 0.70) compared to those with BMI <25 and 2) in males compared to females (SBP: r = 0.71, DBP: r = 0.77). Conclusions In our patients a CL-BP device estimated 24 h mean SBP and DBP differently from the classical oscillometric device, with a moderate correlation. CL-BP measurements were most accurate on male and overweight subjects

Compassionate use of ruxolitinib in patients with SARS‐Cov‐2 infection not on mechanical ventilation: Short‐term effects on inflammation and ventilation

Abstract Ruxolitinib is an anti‐inflammatory drug that inhibits the Janus kinase‐signal transducer (JAK‐STAT) pathway on the surface of immune cells. The potential targeting of this pathway using JAK inhibitors is a promising approach in patients affected by coronavirus disease 2019 (COVID‐19). Ruxolitinib was provided as a compassionate use in patients consecutively admitted to our institution for severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection. Inclusion criteria were oxygen saturation less than or equal to 92%, signs of interstitial pneumonia, and no need of mechanical ventilation. Patients received 5 mg b.i.d. of ruxolitinib for 15 days, data were collected at baseline and on days 4, 7, and 15 during treatment. Two main targets were identified, C‐reactive protein (CRP) and PaO2/FiO2 ratio. In the 31 patients who received ruxolitinib, symptoms improved (dyspnea scale) on day 7 in 25 of 31 patients (80.6%); CRP decreased progressively from baseline (79.1 ± 73.4 mg/dl) to day 15 (18.6 ± 33.2, p = 0.022). In parallel with CRP, PO2/FiO2 ratio increased progressively during the 3 steps from 183 ± 95 to 361 ± 144 mmHg (p < 0.001). In those patients with a reduction of polymerase chain reaction less than or equal to 80%, delta increase of the PO2/FiO2 ratio was significantly more pronounced (129 ± 118 vs. 45 ± 35 mmHg, p = 0.02). No adverse side effects were recorded during treatment. In patients hospitalized for COVID‐19, compassionate‐use of ruxolitinib determined a significant reduction of biomarkers of inflammation, which was associated with a more effective ventilation and reduced need for oxygen support. Data on ruxolitinib reinforces the hypothesis that targeting the hyperinflammation state, may be of prognostic benefit in patients with SARS‐CoV‐2 infection. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Some evidence suggest that patients affected by coronavirus disease 2019 (COVID‐19) present an exuberant inflammatory response represented by a massive production of type I interferons and different pro‐inflammatory cytokines. Nonetheless, as for the present, there are no proven therapeutic agents for COVID‐19, in particular anti‐inflammatory and antiviral, with a significant and reproducible positive clinical response. WHAT QUESTION DID THIS STUDY ADDRESS? Targeted therapeutic management of pro‐inflammatory pathways appears to be a promising strategy against COVID‐19, and ruxolitinib, due to its established broad and fast anti‐inflammatory effect, appears to be a promising candidate worthy of focused investigations in this field. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Ruxolitinib rapidly reduces the systemic inflammation, which accompanies the disease, thereby improving respiratory function and the need of oxygen support. This effect may contribute to avoid progression of the disease and the use of invasive ventilation. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Data on ruxolitinib contributes the reinforcement of the hypothesis that it is crucial to counteract the early hyperinflammation state, particularly of the lungs, induced by COVID‐19 infection

Left atrial appendage occlusion after thromboembolic events or left atrial appendage sludge during anticoagulation therapy: Is two better than one? Real-world experience from a tertiary care hospital

BackgroundThe role of left atrial appendage occlusion (LAAO) for atrial fibrillation patients that during oral anticoagulant therapy (OAC) suffer from ischemic events or present LAA sludge, and the best postinterventional anticoagulant regimen, need to be defined. We present our experience with a hybrid approach of LAAO+ lifelong OAC therapy in this cohort of patients. MethodsOut of 425 patients treated with LAAO, 102 underwent LAAO because, despite OAC, suffered from ischemic events or presented with LAA sludge. Patients without high bleeding risk were discharged with the aim of maintaining lifelong OAC. This cohort was then matched to a population who underwent LAAO in primary ischemic events prevention. The primary endpoint was the composite of all-cause death and major adverse cardiovascular events consisting of ischemic stroke, systemic embolism (SE), and major bleeding. ResultsProcedural success was 98%, and 70% of patients were discharged with anticoagulant therapy. After a median follow-up of 47.2 months, the primary endpoint occurred in 27 patients (26%). At multivariate analyses, coronary artery disease (OR 5.1, CI 1.89-14.27, p = .003) and OAC at discharge (OR 0.29, CI 0.11-0.80, p = .017) were associated with the primary endpoint. After propensity score matching, no significant difference was found in the survival free from the primary endpoint according to the indication for LAAO (p = .19). ConclusionsIn this high-ischemic risk cohort, LAAO + OAC seem a long-term safe and effective therapeutical approach, with no difference in the survival free from the primary endpoint according to the indication for LAAO in a matched cohort

Prognostic value of right ventricular longitudinal strain in patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge mitral valve repair

Aims To evaluate the prognostic impact of pre-procedural right ventricular longitudinal strain (RVLS) in patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge repair (TEER) in comparison with conventional echocardiographic parameters of RV function. Methods and results This is a retrospective study including 142 patients with SMR undergoing TEER at two Italian centres. At 1-year follow-up 45 patients reached the composite endpoint of all-cause death or heart failure hospitalization. The best cut-off value of RV free-wall longitudinal strain (RVFWLS) to predict outcome was -18% [sensitivity 72%, specificity of 71%, area under curve (AUC) 0.78, P = -18% vs. RVFWLS = -15% vs. RVGLS < -15% (54.9% vs. 81.7%; P < 0.001). At multivariable analysis FAC, RVGLS and RVFWLS were independent predictors of events. The identified cut-off of RVFWLS and RVGLS both resulted independently associated with outcomes. Conclusion RVLS is a useful and reliable tool to identify patients with SMR undergoing TEER at high risk of mortality and HF hospitalization, on top of other clinical and echocardiographic parameters, with RVFWLS offering the best prognostic performance

Pulmonary embolism in patients with COVID-19: characteristics and outcomes in the Cardio-COVID Italy multicenter study

BACKGROUND: Pulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited.METHODS: Data were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between D-dimer levels and PE incidence was evaluated using restricted cubic splines models.RESULTS: The study included 689 patients (67.3\ub113.2year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9-24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission D-dimer [4344 (1099-15,118) vs. 818.5 (417-1460) ng/mL, p<0.001]. They also received more frequently darunavir/ritonavir, tocilizumab and ventilation support. Furthermore, they faced more bleeding episodes requiring transfusion (15.6% vs. 5.1%, p<0.001) and non-significantly higher in-hospital mortality (34.6% vs. 22.9%, p=0.06). In multivariate regression, only D-dimer was associated with PE (HR 1.72, 95% CI 1.13-2.62; p=0.01). The relation between D-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline D-dimer<500ng/mL.CONCLUSIONS: PE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of D-dimer in this population need to be clarified

Effect of Chronic Kidney Disease on 5-Year Outcome in Patients With Heart Failure and Secondary Mitral Regurgitation Undergoing Percutaneous MitraClip Insertion

Chronic kidney disease (CKD) is strongly related to outcomes in cardiovascular diseases. Limited data are available regarding the independent prognostic role of CKD after transcatheter mitral valve repair with MitraClip. We sought to evaluate the real impact of CKD in a large series of patients with heart failure (HF) and secondary mitral regurgitation (SMR) who underwent MitraClip treatment. The study included 565 patients with severe SMR from a multicenter international registry. Patients were stratified into 3 groups according to estimated glomerular filtration rate (eGFR) assessment before MitraClip implantation: normal eGFR (≥60&nbsp;ml/min/1.73&nbsp;m2) (n&nbsp;=&nbsp;196), mild-to-moderate CKD (30 to 59&nbsp;ml/min/1.73&nbsp;m2) (n&nbsp;=&nbsp;267), and severe CKD (&lt;30&nbsp;ml/min/1.73&nbsp;m2) (n&nbsp;=&nbsp;102). The primary end point was a composite of overall death and the first rehospitalization for HF, the secondary end points were overall death, cardiac death, and first rehospitalization for HF. CKD was present in about 2/3 of patients. At 5-year Kaplan-Meier analysis, primary clinical end point occurred in 60% of patients with normal eGFR, compared with 73% cases in patients with mild-to-moderate CKD and 91% in patients with severe CKD (p&nbsp;&lt;0.001). Long-term overall death rate significantly decreased with increasing eGFR, and cardiac death and rehospitalization for HF rates. Multivariate Cox regression analysis identified severe CKD as the strongest independent predictor of adverse outcome (hazard ratio 2.136, 95% confidence interval 1.164 to 3.918, p&nbsp;=&nbsp;0.014). In conclusion, CKD affected about 2/3 of patients who underwent MitraClip treatment for severe SMR, and it was a strong and independent predictor of 5-year adverse outcomes

Pulmonary embolism in patients with COVID&#8209;19: characteristics and outcomes in the Cardio&#8209;COVID Italy multicenter study

BackgroundPulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited.MethodsData were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between d-dimer levels and PE incidence was evaluated using restricted cubic splines models.ResultsThe study included 689 patients (67.3 \ub1 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9\u201324) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involve-ment, and higher admission d-dimer [4344 (1099\u201315,118) vs. 818.5 (417\u20131460) ng/mL, p &lt; 0.001]. They also received more frequently darunavir/ritonavir, tocilizumab and ventilation support. Furthermore, they faced more bleeding episodes requiring transfusion (15.6% vs. 5.1%, p &lt; 0.001) and non-significantly higher in-hospital mortality (34.6% vs. 22.9%, p = 0.06). In multivariate regression, only d-dimer was associated with PE (HR 1.72, 95% CI 1.13\u20132.62; p = 0.01). The rela-tion between d-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline d-dimer &lt; 500 ng/mL.ConclusionsPE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of d-dimer in this population need to be clarified