[Optimizing the care management pathway of patients with ischemia and non-obstructive coronary arteries]. / Ottimizzazione del percorso clinico-gestionale del paziente con ischemia in assenza di malattia coronarica ostruttiva.

Ischemia with non-obstructive coronary arteries (INOCA) is defined by the coexistence of anginal symptoms and demonstrable ischemia, with no evidence of obstructive coronary arteries. The underlying mechanism of INOCA is coronary microvascular dysfunction with or without associated vasospasm. INOCA patients have recurrent symptoms, functional limitations, repeated access to the emergency department, impaired quality of life and a higher incidence of cardiovascular events than the general population. Although well described in chronic coronary syndrome guidelines, INOCA remains underdiagnosed in clinical practice because of insufficient awareness, lack of accurate diagnostic tools, and poorly standardized and consistent definitions to diagnose, both invasively and non-invasively, coronary microvascular dysfunction.To disseminate current scientific evidence on INOCA as a distinct clinical entity, during 2022 we conducted at 30 cardiology units all over the country a clinical practice improvement initiative, with the aim of developing uniform and shared management pathways for INOCA patients across different operational settings. The present document highlights the outcomes of this multidisciplinary initiative.

Gastric protection in cardiological practice: an Italian survey on the prescriptive attitude.

BACKGROUND: Gastric protection is commonly considered in patients who use medications able to damage gastric mucosa, mainly NSAIDs, antiplatelets, and anticoagulants. Therefore, cardiologists may frequently prescribe drugs to protect the stomach from damaging medications. The present survey investigated the attitude toward using gastric protection by a panel of Italian cardiologists. METHODS: A self-administered questionnaire included three sections concerning practical problems on this issue in clinical practice facing patients with cardiological disorders. The questionnaire was administered in three successive months. RESULTS: Ninety Italian cardiologists completed the questionnaire. They all consider gastric protection, mainly when prescribing potentially noxious medications. Usually, cardiologists prescribe proton pump inhibitors (PPIs) in 60% of their patients. Alginates and mucosal protectors are less considered. As a rule, cardiologists request investigations if the initial treatment fails. Moreover, the safety issue is carefully assessed. Furthermore, this survey experience significantly affected the approach to managing patients who require gastric protection. The participants carefully considered the prescriptive appropriateness of gastric protectors, mainly concerning the PPIs use. Consequently, PPIs were discontinued when inappropriate. A new medical device with triple action (antacid, mucosal protectors, and anti-reflux) contributed to this new attitude. CONCLUSIONS: The present survey underscored that the appropriateness in prescribing gastric protectors is clinically relevant. In addition, a longitudinal survey experience contributed to change the practical approach by highlighting the prescriptive appropriateness of PPIs, and using a new medical device with multiple gastroprotective activities.

Clinical and functional effects of beta-blocker therapy discontinuation in patients with biventricular heart failure.

BACKGROUND: Nearly two-thirds of patients with heart failure with reduced ejection fraction (HFrEF) have right ventricular dysfunction, previously identified as an independent predictor of reduced functional capacity and poor prognosis. Beta-blocker therapy (ß-BT) reduces mortality and hospitalizations in patients with HFrEF and is approved as first-line therapy regardless of concomitant right ventricular function. However, the exact role of sympathetic nervous system activation in right ventricular dysfunction and the potential usefulness (or harmfulness) of ß-BT in these patients are still unclear. OBJECTIVES: The aim of the study is to evaluate the medium-term effect of ß-BT discontinuation on functional capacity and right ventricular remodelling based on cardiopulmonary exercise testing (CPET), echocardiography and serum biomarkers in patients with clinically stable biventricular dysfunction. METHODS: In this single-centre, open-label, prospective trial, 16 patients were enrolled using the following criteria: patients were clinically stable without signs of peripheral congestion; NYHA II-III while on optimal medical therapy (including ß-BT); LVEF 40% or less; echocardiographic criteria of right ventricular dysfunction. Patients were randomized 1 : 1 either to withdraw (group 0) or continue (group 1) ß-BT. In group 0, optimal heart rate was obtained with alternative rate-control drugs. Echo and serum biomarkers were performed at baseline, after 3 and 6 months; CPET was performed at baseline and 6 months. Mann--Whitney U test was adopted to determine the relationships between ß-BT discontinuation and effects on right ventricular dysfunction. RESULTS: At 6 months' follow up, S' DTI improved (ΔS': 1.01 vs. -0.92 cm/s; P = 0.03), while estimated PAPs (ΔPAPs: 0.8 vs. -7.5 mmHg; P = 0.04) and echo left ventricular-remodelling (ΔEDVi: 19.55 vs. -0.96 ml/mq; P = 0.03) worsened in group 0. In absolute terms, the only variables significantly affected by ß-BT withdrawal were left ventricular EDV and ESV, appearing worse in group 0 (mean EDVi 115 vs. 84 ml/mq; mean ESVi 79 vs. 53.9 ml/mq, P = 0.03). No significant changes in terms of functional capacity were observed after ß-BT withdrawal. CONCLUSION: In HFrEF patients with concomitant right ventricular dysfunction, ß-BT discontinuation did not produce any beneficial effects. In addition, despite maintenance of optimal heart rate control, ß-BT discontinuation induced worsening of left ventricular remodelling. Our study corroborates the hypothesis that improvement in left ventricular function may likewise be a major determinant for improvement in right ventricular function, reducing pulmonary wedge pressure and right ventricular afterload, with only a marginal action of its negative inotropic effect. In conclusion, ß-BT appears beneficial also in heart failure patients with biventricular dysfunction.

Baseline Characteristics and 3-Year Outcome of Nonvalvular Atrial Fibrillation Patients Treated with the Four Direct Oral Anticoagulants (DOACs).

Direct oral anticoagulants (DOACs) represent the cornerstone therapy for cardioembolic events prevention in patients with nonvalvular atrial fibrillation (NVAF). In practice, the choice of one DOAC over another is guided by the decision-making process of the physician, which considers specific patient and drug characteristics. This study aimed to evaluate the clinical features and long-term outcomes of a real-world population treated with DOACs, where the use of the 4 different DOACs is quite equal. We conducted a retrospective observational, single-center, multidisciplinary study enrolling consecutive NVAF patients treated with one of the 4 DOACs. From an initial number of 753 patients, we excluded 72 patients because of loss to follow-up, at the end we enrolled 681:174 (23%) treated with dabigatran, 175 (23%) with apixaban, 190 (25%) with rivaroxaban, and 214 (29%) with edoxaban. Patients treated with apixaban were significantly older, more women represented (p <0.001), and with a higher cardioembolic and bleeding risk (p <0.001). Dabigatran was preferred in patients with liver failure (p = 0.008), whereas Apixaban and Edoxaban were chosen in chronic kidney disease (p = 0.002). At 3-year follow-up, 20 patients (2.7%) experienced a systemic thromboembolic event without significant differences in the 4 DOACs. In the same period, an International Society of Thrombosis and Hemostasis classification major bleeding event occurred in 26 patients (3.6%), more statistically correlated to edoxaban (6.1%) (p = 0.038). Thromboembolic events or major bleeding were higher in the edoxaban group (10%) compared with the others (p = 0.014). In our single-center real-world experience, the choice of the DOAC for a patient with NVAF was tailored to specific clinical features and drug pharmacokinetics of the patient. As a result, a small number of adverse events were observed.

Direct oral anticoagulants versus percutaneous left atrial appendage occlusion in atrial fibrillation: 5-year outcomes.

BACKGROUND: LAAO is an emerging option for thromboembolic event prevention in patients with NVAF. We previously reported data on comparison between LAAO and DOAC at two-year follow-up in NVAF patients at HBR (HAS-BLED ≥3). AIMS: Limited data are available on long term follow-up. We aimed to evaluate the efficacy and safety of DOACs versus LAAO indication after 5 years. METHODS: We enrolled 193 HBR treated with LAAO and 189 HBR patients with DOACs. At baseline, LAAO group had higher HAS-BLED (4.2 vs 3.3, p < 0.001) and lower CHADS-VASc (4.3 vs. 4.7, p = 0.005). After 1:1 PSM, 192 patients were included (LAAO n = 96; DOACs n = 96). RESULTS: At 5-year follow-up the rate of the combined safety and effectiveness endpoint (ISTH major bleeding and thromboembolic events) was significantly higher in LAAO group (p = 0.042), driven by a higher number of thromboembolic events (p = 0.047). The rate of ISTH-major bleeding events was similar (p = 0.221). After PSM no significant difference in the primary effectiveness (LAAO 13.3% vs DOACs 9.5%, p = 0.357) and safety endpoint (LAAO 7.5% vs DOACs 7.5%; p = 0.918) were evident. Overall bleeding rate was significantly higher in DOACs group (25.0% vs 13.7%, p = 0.048), while a non-significant higher number of TIA was reported in LAAO group (5.4% vs 1.1%, p = 0.098). All-cause and cardiovascular mortality were higher in LAAO group at both unmatched and matched analysis. CONCLUSION: We confirmed safety and effectiveness of both DOAC and LAAO in NVAF patients at HBR, with no significant differences in thromboembolic events or major bleeding were at 5-year follow-up. The observed increased mortality after LAAO warrants further investigations in RCTs.

Potential Cardiologic Protective Effects of Acetylcholinesterase Inhibitors in Patients With Mild to Moderate Dementia.

In patients with mild to moderate dementia, acetylcholinesterase inhibitors (AChE-I) are used to improve cognitive functions, but bradycardia, conduction abnormalities, and hypotension are possible side effects because of the peripheral muscarinic M2 receptor stimulation. This study aimed to evaluate the main cardiologic clinical outcomes in patients with dementia who are on AChE-I. In this retrospective, monocentric, observational cohort study, 2 groups were considered: (1) patients with dementia because of the typical and atypical forms of Alzheimer disease treated with AChE-I and (2) cognitively unimpaired, matched control group. The primary end point was a composite of cardiovascular death, nonfatal acute myocardial infarction, myocardial revascularization, occurrence of stroke and/or transient ischemic attacks, and hospitalization for heart failure occurring during a mean of 3.1 years of follow-up. The secondary end points were each individual component of the primary end point, total mortality, noncardiovascular death, and incidence of pacemaker implant. Each group included 221 patients who were homogeneous in terms of age, gender, and main cardiovascular risk factors. Major adverse cardiovascular events occurred in 24 patients with dementia (2.1 per 100 patient-years) compared with 56 in control group (5.0 per 100 patient-years), p = 0.036. Even if not significant, the difference was mainly driven by myocardial revascularization (3.2% vs 6.8%) and hospitalization for heart failure (4.5% vs 14.5%). As expected, noncardiovascular mortality was significantly higher in the treatment group (13.6% vs 2.7% p = 0.006). No significant difference between the groups was observed in terms of other secondary outcomes. In conclusion, in patients with dementia, the use of AChE-I may be protective for cardiovascular outcomes, especially in reducing heart failure hospitalization and myocardial revascularization.

2-year outcomes of MitraClip as a bridge to heart transplantation: The international MitraBridge registry.

BACKGROUND: In the first report from the MitraBridge registry, MitraClip as a bridge to heart transplantation (HTx) proved to be at 1-year an effective treatment strategy for 119 patients with advanced heart failure (HF) who were potential candidates for HTx. We aimed to determine if benefits of MitraClip procedure as a bridge-to-transplant persist up to 2-years. METHODS: By the end of the enrollment period, a total of 153 advanced HF patients (median age 59 years, left ventricular ejection fraction 26.9 ± 7.7%) with significant secondary mitral regurgitation, who were potential candidates for HTx and were treated with MitraClip as a bridge-to-transplant strategy, were included in the MitraBridge registry. The primary endpoint was the 2-year composite adverse events rate of all-cause death, first hospitalization for HF, urgent HTx or LVAD implantation. RESULTS: Procedural success was achieved in 89.5% of cases. Thirty-day mortality was 0%. At 2-year, Kaplan-Meier estimates of freedom from primary endpoint was 47%. Through 24 months, the annualized rate of HF rehospitalization per patient-year was 44%. After an overall median follow-up time of 26 (9-52) months, elective HTx was successfully performed in 30 cases (21%), 19 patients (13.5%) maintained or obtained the eligibility for transplant, and 32 patients (22.5%) no longer had an indication for HTx because of significant clinical improvement. CONCLUSIONS: After 2-years of follow-up, the use of MitraClip as a bridge-to-transplant was confirmed as an effective strategy, allowing elective HTx or eligibility for transplant in one third of patients, and no more need for transplantation in 22.5% of cases.

Performances of HEART score to predict 6-month prognostic of emergency department patients with chest pain: a retrospective cohort analysis.

BACKGROUND AND IMPORTANCE: Chest pain is a frequent cause of patient admissions in emergency departments (EDs). Clinical scores can help in the management of chest pain patients with an undefined impact on the appropriateness of hospitalization or discharge when compared to usual care. OBJECTIVES: The aim of this study was to assess the performances of the HEART score to predict the 6-month prognostic of patients presenting to the ED of a tertiary referral university hospital with non-traumatic chest pain. DESIGN, SETTINGS, AND PARTICIPANTS: From 7040 patients presenting with chest pain from 1 January 2015 to 31 December 2017, after applying exclusion criteria (ST-segment elevation >1 mm, shock, absence of telephone number) we selected a sample of 20% chosen randomly. We retrospectively assessed the clinical course, definitive diagnosis, and HEART score according to ED final report. Follow-up was made by telephone interview with discharged patients. In hospitalized patients, clinical records were analyzed to evaluate major adverse cardiac events (MACE) incidence. OUTCOME MEASURE AND ANALYSIS: The primary endpoint was MACE, comprising cardiovascular death, myocardial infarction, or unscheduled revascularization at 6 months. We assessed the diagnostic performance of the HEART score in ruling out MACE at 6 months. We also assessed the performance of ED usual care in the management of chest pain patients. RESULTS: Of 1119 screened, 1099 were included for analysis after excluding patients lost to follow-up; 788 patients (71.70%) had been discharged and 311 (28.30%) were hospitalized. Incident MACE was 18.3% ( n  = 205). The HEART score was retrospectively calculated in 1047 patients showing increasing MACE incidence according to risk category (0.98% for low risk, 38.02% for intermediate risk, and 62.21% for high risk). Low-risk category allowed to safely exclude MACE at 6 months with a negative predictive value (NPV) of 99%. Usual care diagnostic performance showed 97.38% sensitivity, 98.24% specificity, 95.5% positive predictive value, and 99% NPV, with an overall accuracy of 98.00%. CONCLUSIONS: In ED patients with chest pain, a low HEART score is associated with a very low risk of MACE at 6 months.

Concomitant Transcatheter Edge-to-Edge Treatment of Secondary Tricuspid and Mitral Regurgitation: An Expert Opinion.

Secondary (functional) tricuspid regurgitation (sTR) is common in patients with mitral regurgitation (MR). Because combined valvular heart disease affects long-term survival, in comparison with isolated MR or tricuspid regurgitation, it is essential to offer patients adequate treatment. Despite considerable experience, no conclusive data are yet available on the prognostic impact of concomitant tricuspid valve surgery at the time of mitral valve surgery. Emerging transcatheter treatments offer the opportunity to treat both conditions (MR and sTR) simultaneously or in a stepwise fashion. This review provides a clinical overview on available data regarding the rationale for treatment of sTR in patients with relevant MR undergoing mitral transcatheter edge-to-edge repair, focusing on clinical and anatomical selection criteria.

Left atrial appendage closure: a new strategy for cardioembolic events despite oral anticoagulation.

BACKGROUND: Patients with non-valvular atrial fibrillation (nvAF) who experienced a cardioembolic (CE) event despite adequate oral anticoagulation (OAC) are at high risk of recurrence, and further prevention strategies are deemed necessary. The present study aimed to evaluate the safety and efficacy of off-label use of left atrial appendage closure (LAAC) in this subset of patients. METHODS: Seventy-five consecutive patients with nvAF who experienced a CE event despite adequate OAC therapy were retrospectively enrolled from two Italian centers. Patients were divided according to the treatment strategy following the index event: DOAC group (49 patients who continued OAC therapy with DOACs) and LAAC group (26 patients who underwent LAAC procedure). 1:1 propensity-score matching between the two groups was performed. LAAC group was made up of two subgroups according to the post-procedural pharmacological regimen: 1) dual antiplatelet therapy (DAPT) for 3 months followed by indefinite single antiplatelet therapy (LAAC+SAPT); or 2) aspirin plus DOAC for 3 months followed by indefinite DOAC therapy (LAAC+DOAC). The primary endpoint was a composite of CE event, major bleeding, or procedure-related major complication. RESULTS: During a median follow-up of 3.4 years (IQR: 2.0-5.3), LAAC was a predictor of primary endpoint-free survival (HR=0.28, 95% CI: 0.08-0.97; P=0.044); within LAAC group, no procedure-related major complication occurred. Moreover, a trend toward a lower rate of both CE events and major bleedings was observed in LAAC group, particularly in the subgroup LAAC+DOAC. CONCLUSIONS: LAAC is a reasonable therapeutic option in nvAF patients who suffered a CE event despite adequate OAC therapy.

Safety and efficacy of direct oral anticoagulants (DOACs) in very elderly patients (≥85 years old) with non-valvular atrial fibrillation.

BACKGROUND: Limited real-world data are available regarding the comparison about safety and efficacy of DOACs prescription in very elderly patients (≥85 years) with non-valvular atrial fibrillation (NVAF). Concern about the risk of bleeding with anticoagulation in very older patients still represents an important challenge for clinicians. The aim of this study was to evaluate the different prevalence of major bleeding and thromboembolic events between very elderly NVAF patients (≥85 years) compared to those non very elderly (<85 years). METHODS: Single center multidisciplinary registry including NVAF patients treated with DOACs. Primary safety endpoint was 2-year rate of major bleeding. Primary efficacy endpoint was 2-year rate of thromboembolic events. Event-free survival curves among groups were compared using Cox-Mantel Test. RESULTS: 908 NVAF consecutive patients were included, of these, 805 patients were <85 years (89%) and 103 patients were very elderly patients with ≥85 years (11%). Compared to patients <85 years, those very elderly have higher CHA2DS2-VASc Score (P=0.001), higher rate of hypertension (P=0.001), diabetes mellitus (P=0.030), previous bleeding events (P<0.001), previous stroke/TIA/SE (P≤0.001), heart failure (P≤0.001), and lower creatinine clearance (P<0.001). In terms of safety endpoints (overall ISTH-major bleeding) no significative difference between two groups (P=0.952) were observed up to 2-year follow-up. Systemic thromboembolic event (primary efficacy endpoint) was significantly higher in patients with ≥85 years (P=0.027). The incidence of all-cause death was significantly higher in very elderly patients (P<0.001). CONCLUSIONS: This single center registry, showed that the use of DOACs in very elderly NVAF was safe and is a therapeutic option to be pursued for stroke prevention especially for those who are at high risk of ischemic events.

A comprehensive and easy-to-use ECG algorithm to predict the coronary occlusion site in ST-segment elevation myocardial infarction.

BACKGROUND: Several electrocardiogram (ECG) criteria have been proposed to predict the location of the culprit occlusion in specific subsets of patients presenting with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to develop, through an independent validation of currently available criteria, a comprehensive and easy-to-use ECG algorithm, and to test its diagnostic performance in real-world clinical practice. METHODS: We analyzed ECG and angiographic data from 419 consecutive STEMI patients submitted to primary percutaneous coronary intervention over a one-year period, dividing the overall population into derivation (314 patients) and validation (105 patients) cohorts. In the derivation cohort, we tested >60 previously published ECG criteria, using the decision-tree analysis to develop the algorithm that would best predict the infarct-related artery (IRA) and its occlusion level. We further assessed the new algorithm diagnostic performance in the validation cohort. RESULTS: In the derivation cohort, the algorithm correctly predicted the IRA in 88% of cases and both the IRA and its occlusion level (proximal vs mid-distal) in 71% of cases. When applied to the validation cohort, the algorithm resulted in 88% and 67% diagnostic accuracies, respectively. In a real-world comparative test, the algorithm performed significantly better than expert physicians in identifying the site of the culprit occlusion (P = .026 vs best cardiologist and P < .001 vs best emergency medicine doctor). CONCLUSIONS: Derived from an extensive literature review, this comprehensive and easy-to-use ECG algorithm can accurately predict the IRA and its occlusion level in all-comers STEMI patients.

Derivation and Validation of a Clinical Risk Score for COAPT-Ineligible Patients Who Underwent Transcatheter Edge-to-Edge Repair.

Up to half of real-world patients with secondary mitral regurgitation who underwent transcatheter edge-to-edge repair (TEER) do not meet the highly selective COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) criteria. No randomized trials or standardized and validated tools exist to evaluate the risk: benefit ratio of TEER in this specific population. We sought to derive and externally validate a clinical risk score to predict the risk of death or heart failure (HF) hospitalization for COAPT-ineligible patients who underwent TEER (CITE score). The study population consisted of patients with secondary mitral regurgitation having at least 1 exclusion criterion of the COAPT trial. The derivation cohort included 489 patients from the GIOTTO (GIse registry of Transcatheter treatment of Mitral Valve regurgitaTiOn) registry. Cox proportional hazards regression was used to identify predictors of 2-year death/HF hospitalization and develop a numerical risk score. The predictive performance was assessed in the derivation cohort and validated in 268 patients from the MiZüBr (Milan-Zürich-Brescia) registry. The CITE score (hemodynamic instability, left ventricular impairment, New York Heart Association class III/IV, peripheral artery disease, atrial fibrillation, brain natriuretic peptide, and hemoglobin) showed a c-index for 2-year death or HF hospitalization of 0.70 (95% confidence interval [CI] 0.67 to 0.73) in the derivation cohort, and 0.68 (95% CI 0.64 to 0.73) in the validation cohort. A cutoff of <12 points was selected to identify patients at lower risk of adverse outcomes, hazard ratio of 0.35 (95% CI 0.26 to 0.46). In conclusion, the CITE score is a simple 7-item tool for the prediction of death or HF hospitalization at 2 years after TEER in COAPT-ineligible patients. The score may support clinical decision-making by identifying those patients who, even if excluded from clinical trials, can still benefit from TEER.

Effectiveness and cost-efficacy of diuretics home administration via peripherally inserted central venous catheter in patients with end-stage heart failure.

BACKGROUND: End-stage heart failure (ESHF) is characterized by severe cardiac dysfunction with persistent disabling symptoms and recurrent acute decompensated heart failure (ADHF), despite guideline-directed medical therapy. The aim of this study was to evaluate the efficacy and safety of intravenous diuretics administration at home through a peripherally inserted central venous catheter (PICC) in ESHF patients. METHODS AND RESULTS: Forty-one ESHF patients received PICC implantation for intravenous diuretic administration at home. The primary efficacy endpoint was the patient-level number of HF hospitalizations in the short (1-3 months), medium (six months), and long term (1 year), before and after PICC implantation. Pre- and post-PICC ADHF-free days were also evaluated as co-primary endpoint. Secondary endpoints comprised changes in clinical, laboratory and echocardiographic parameters, and device safety. A cost-effectiveness analysis was performed to estimate the economic impact of using PICC. For each time frame analyzed, a significant reduction in the number of hospitalizations due to ADHF was observed, resulting in a significant increase in ADHF-free days (71 ± 44 vs. 163 ± 136, p = 0.003). In matched patients' analysis, significant decrease in body weight (68 ± 16 kg vs. 63 ± 10 kg, p = 0.041) and mitral regurgitation grade 3/4 (55% vs. 18%, p < 0.001) were also observed. Freedom from PICC-related complications was observed in 61% of patients. A significant reduction in overall ADHF-hospitalizations cost was observed. CONCLUSIONS: This proof-of-concept study demonstrates the effectiveness and safety of home administration of intravenous diuretic therapy via PICC in ESHF patients. This palliative cost-effective strategy can be taken in consideration for selected end-stage patients no longer responsive to conventional therapies.

Myocardial fibrosis in asymptomatic patients undergoing surgery for mitral and aortic valve regurgitation.

BACKGROUND: Chronic heart valve regurgitation induces left ventricular (LV) volume overload, leading to the development of hypertrophy and progressive dilatation of the ventricle to maintain physiological cardiac output. In order to prevent potential irreversible LV structural changes, the identification of the best timing for treatment is pivotal. OBJECTIVE: To assess the presence and extent of fibrosis in myocardial tissue in asymptomatic patients with valvular heart disease (VHD) and preserved LV dimensions and function undergoing cardiac surgery. METHODS: Thirty-nine patients were enrolled. Sixteen patients were affected by aortic or mitral regurgitation: they were all asymptomatic, undergoing valve surgery according to VHD European Society of Cardiology guidelines. Twenty-three patients with end-stage nonischemic dilated cardiomyopathy (DCM) and severe LV dysfunction undergoing cardiac surgery for implantation of a durable left ventricular assist device (LVAD) served as controls. During surgery, VHD patients underwent three myocardial biopsies at the level of the septum, the lateral wall and LV apex, while in LVAD patients the coring of the apex of the LV was used. For both groups, the tissue samples were analyzed on one section corresponding to the apical area. All slides were stained with hematoxylin and eosin and Masson's trichrome staining and further digitalized. The degree of fibrosis was then calculated as a percentage of the total area. RESULTS: Of 39 patients, 23 met the inclusion criteria: 12 had mitral or aortic insufficiency with a preserved ejection fraction and 11 had idiopathic dilated cardiomyopathy. Quantitative analysis of apical sections revealed a myocardial fibrosis amount of 10 ±â€Š6% in VHD patients, while in LVAD patients the mean apical myocardial fibrosis rate was 38 ±â€Š9%. In VHD patients, fibrosis was also present in the lateral wall (9 ±â€Š4%) and in the septum (9 ±â€Š6%). CONCLUSION: Our case series study highlights the presence of tissue remodeling with fibrosis in asymptomatic patients with VHD and preserved LV function. According to our results, myocardial fibrosis is present at an early stage of the disease, well before developing detectable LV dysfunction and symptoms. Since the relationship between the progressive magnitude of myocardial fibrosis and potential prognostic implications are not yet defined, further studies on this topic are warranted.

Meta-Analysis of Relation Between Left Ventricular Dysfunction and Outcomes After Transcatheter Mitral Edge-to-Edge Repair.

Randomized controlled trials (RCTs) and observational studies provided conflicting results regarding the role of left ventricular (LV) function on outcomes after transcatheter edge-to-edge repair (TEER). The study aimed to provide a comprehensive assessment of the interplay between severe LV dysfunction and TEER outcomes. Multiple electronic databases, including PubMed, EMBASE, Scopus, Web of Science, and CENTRAL, were searched to identify studies on TEER for secondary mitral regurgitation reporting outcomes stratified for LV ejection fraction <30% and ≥30%. The prespecified primary end points were the composite of all-cause death or heart failure (HF) hospitalization and New York Heart Association (NYHA) class III/IV. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by random-effects models. Multiple sensitivity analyses accounting for baseline characteristics and study design were applied. A total of 6 studies (1,957 patients) with 1 year or 2 years of follow-up were available. Severe LV dysfunction was associated with an increased risk of death or HF hospitalization (OR 1.71, 95% CI 1.14 to 2.57). Conversely, comparable rates of NYHA class III/IV (OR 1.06, 95% CI 0.82 to 1.38) or secondary end points (reinterventions, recurrence of significant secondary mitral regurgitation) were found regardless of the baseline LV function. Subgroup meta-analysis found no difference in the composite primary end point between patients with LV ejection fraction <30% and ≥30% enrolled in RCTs. In conclusion, TEER seems to be associated with higher mortality or HF hospitalization rates in patients with severe LV dysfunction. However, RCTs found no differences between groups. No impact of LV function was found on the risk of NYHA class III/IV or other clinical outcomes.

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 ml/min/1.73 m2) (n = 196), mild-to-moderate CKD (30 to 59 ml/min/1.73 m2) (n = 267), and severe CKD (<30 ml/min/1.73 m2) (n = 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 <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 = 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.

Vasostatin-1 as a potential novel circulating biomarker in patients with chronic systolic heart failure: A pilot study.

BACKGROUND AND AIMS: Previous studies have shown that circulating chromogranin A (CgA) increases in patients with chronic systolic heart failure (HF). Aim of the present study is to evaluate the potential role of circulating vasostatin-1 (VS-1), a cardioregulatory fragment of CgA, as prognostic marker in patients with chronic HF. MATERIALS AND METHODS: The plasma levels of CgA and VS-1 were determined in 80 patients with chronic systolic HF. Patients were followed-up to evaluate the occurrence of cardiovascular (CV) events. RESULTS: CgA and VS-1 plasma levels were significantly higher in patients with CV events at follow-up. VS-1, but not CgA, was associated to NT-proBNP. No significant association of CgA and VS-1 with left ventricular ejection fraction (LVEF) was observed. CgA, NT-proBNP and age, but not VS-1, were independent predictors of CV events. CONCLUSION: In patients with chronic systolic HF those who experienced CV events had higher levels of VS-1 and CgA. Given its established effect on cardiac cells, the association of VS-1 levels with NT-proBNP levels but not with LVEF, suggests that this fragment might provide complementary information to NT-proBNP and CgA in HF patients.

Role of cardiological specialistic evaluation in patients with chest pain presenting in the emergency department.

AIMS: Aim of this study was to evaluate the impact of cardiological and echocardiographic evaluation in addition to a standard clinical and instrumental approach on diagnostic and prognostic accuracy in patients presenting in the emergency department (ED) with chest pain (CP). Acute coronary syndromes, pulmonary embolism and acute aortic syndromes (AAS) (triple-rule-out/TRO) were considered. METHODS: From 7040 patients presenting with CP from 1 January 2015 to 31 December 2017, we randomly selected a sample of 1119. We retrospectively evaluated the clinical course and definitive diagnosis according to the ED final report. A 6-month follow-up to assess incident acute cardiovascular events was made by telephone interview in discharged patients; in hospitalized patients, clinical records were analyzed to evaluate the appropriateness of admissions. Diagnostic and prognostic accuracy wasd estimated through sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, according to the presence or absence of cardiological and echocardiographic consultation. RESULTS: Complete information of 1099 patients out of 1119 was retrieved. Seven hundred and eighty-eight patients (71.70%) had been discharged, eight inappropriately (0.73%). Three hundred eleven (28.30%) had been hospitalized, 14 (1.27%) inappropriately. Diagnostic performance showed 97.38% sensitivity, 98.24% specificity, 95.5% PPV and 99% NPV, with an overall accuracy of 98.00%. In patients evaluated by the cardiologist in addition to the ED physician (n = 387) we observed an improvement of sensitivity and NPV at the expense of specificity. Among improperly discharged patients, 7/8 had normal troponin, 7/8 normal ECG and only 1 was evaluated by a cardiologist. Only one inappropriately hospitalized patient was not evaluated by a cardiologist. CONCLUSIONS: Early consultation with a cardiologist and echocardiography improves clinical judgment in doubtful cases of CP, increasing diagnostic performance mainly by reducing inappropriate patient discharge and guaranteeing a low rate of inappropriate hospitalizations.

Myocardial Late Contrast Enhancement CT in Troponin-Positive Acute Chest Pain Syndrome.

Background Acute chest pain with mild troponin rise and inconclusive diagnosis after clinical evaluation represents a diagnostic challenge. Triple-rule-out (TRO) CT may exclude coronary artery disease (CAD), as well as acute aortic syndrome and pulmonary embolism, but cannot help identify other causes of myocardial injury. Purpose To investigate the diagnostic value of a comprehensive CT protocol including both an angiographic and a late contrast enhancement (LCE) scan in participants with troponin-positive acute chest pain. Materials and Methods In this prospective study, consecutive patients with troponin-positive acute chest pain or anginal equivalent and inconclusive diagnosis after clinical evaluation (symptoms, markers, electrocardiography, and echocardiography) who underwent TRO CT between June 2018 and September 2020 were enrolled. TRO CT was performed to evaluate the presence of obstructive CAD (stenosis ≥50%), acute aortic syndrome, and pulmonary embolism. If the findings on the TRO CT scan were negative, an LCE CT scan was acquired after 10 minutes to assess the presence and pattern of scar and quantify the myocardial extracellular volume fraction. CT-based diagnoses were compared with diagnoses obtained with reference standard methods, including invasive coronary angiography, cardiac MRI, and endomyocardial biopsy. Results Eighty-four patients (median age, 69 years [interquartile range, 50-77 years]; 45 men) were enrolled. TRO CT helped identify obstructive CAD in 35 participants (42%), acute aortic syndrome in one (1.2%), and pulmonary embolism in six (7.1%). LCE CT scans were acquired in the remaining 42 participants. The following diagnoses were reached with use of LCE CT: myocarditis (22 of 42 participants [52%]), takotsubo cardiomyopathy (four of 42 [10%]), amyloidosis (three of 42 [7.1%]), myocardial infarction with nonobstructed coronary arteries (three of 42 [7.1%]), dilated cardiomyopathy (two of 42 [4.8%]), and negative or inconclusive findings (eight of 42 [19%]). The addition of LCE CT improved the diagnostic rate of TRO CT from 42 of 84 participants (50% [95% CI: 38.9, 61.1]) to 76 of 84 (90% [95% CI: 82.1, 95.8]) (P < .001). Conclusion A CT protocol including triple-rule-out and late contrast enhancement CT scans improved diagnostic rate in participants presenting with acute chest pain syndrome. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Nagpal and Bluemke in this issue.