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.

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.

Anesthesia-Induced Intraprocedural Downgrading of Mitral Regurgitation During Transcatheter Edge-to-Edge Repair.

During transcatheter edge-to-edge repair (TEER), the reduction of functional mitral regurgitation (FMR) severity, compared with baseline evaluation, is not uncommon. Because the procedural strategies are mainly guided by the location and severity of the regurgitant jets, intraprocedural downgrading (ID) of regurgitation severity could affect the procedural strategy and the results. The aim of this study was to evaluate the prevalence of ID during TEER and to compare early and midterm outcomes in patients with and without ID. All patients with moderate-to-severe or severe FMR who underwent TEER in San Raffaele Hospital between 2018 and 2020 were evaluated in this single-center, retrospective study. ID was defined as mild (1+) or moderate (2+) regurgitation degree during intraprocedural evaluation. The outcomes, assessed at discharge and at 2 years of follow-up, were all-cause mortality, heart failure hospitalization, and recurrence of mitral regurgitation >2+. The final study cohort included 55 patients: 42% presented with ID. At discharge, 85.5% of patients achieved regurgitation reduction to 2+ or less: 100% in patients with ID versus 75% in patients without ID, p <0.009. At 2 years, no significant difference in the incidence of all-cause mortality, heart failure hospitalization, and the recurrence of mitral regurgitation >2+ between patients with ID or without ID was found. In conclusion, ID is frequent during TEER in FMR. No baseline characteristics were found to identify this group of patients. In patients with ID, the combination of live intraprocedural imaging and baseline ambulatory assessment of regurgitant jets seems effective in the procedural guiding to achieve a successful and durable mitral repair.

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.

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.

Exercise Stress Test Late after Arrhythmic versus Nonarrhythmic Presentation of Myocarditis.

Background. Exercise stress test (EST) has been scarcely investigated in patients with arrhythmic myocarditis. Objectives. To report the results of EST late after myocarditis with arrhythmic vs. nonarrhythmic presentation. Methods. We enrolled consecutive adult patients with EST performed at least six months after acute myocarditis was diagnosed using gold-standard techniques. Patients with ventricular arrhythmia (VA) at presentation were compared with the nonarrhythmic group. Adverse events occurring during follow-up after EST included cardiac death, disease-related rehospitalization, malignant VA, and proven active myocarditis. Results. The study cohort was composed of 128 patients (age 41 ± 9 y, 70% males) undergoing EST after myocarditis. Of them, 64 (50%) had arrhythmic presentation. EST was performed after 15 ± 4 months from initial diagnosis, and was conducted on betablockers in 75 cases (59%). During EST, VA were more common in the arrhythmic group (43 vs. 4, p < 0.001), whereas signs and symptoms of ischemia were more prevalent in the nonarrhythmic one (6 vs. 1, p = 0.115). By 58-month mean follow-up, 52 patients (41%) experienced adverse events, with a greater prevalence among arrhythmic patients (39 vs. 13, p < 0.001). As documented both in the arrhythmic and nonarrhythmic subgroups, patients had greater prevalence of adverse events following a positive EST (40/54 vs. 12/74 with negative EST, p < 0.001). Electrocardiographic features of VA during EST correlated with the subsequent inflammatory restaging of myocarditis. Nonarrhythmic patients with uneventful EST both on- and off-treatment were free from subsequent adverse events. Conclusions. Late after the arrhythmic presentation of myocarditis, EST was frequently associated with recurrent VA. In both arrhythmic and nonarrhythmic myocarditis, EST abnormalities correlated with subsequent adverse outcomes.

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.

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.

Clinical implication of multimodality imaging of aortic root intramural hematoma.

We present a case of a chronic intramural haematoma of the aortic root discovered in the setting of an acute coronary syndrome. We investigated the nature of the lesion through echocardiography, computed-tomography, magnetic resonance and positron emission tomography. In conclusion, the use of complex multimodality imaging led to the final diagnosis and allowed to define the proper management of the lesion.

Hyperhidrosis: the neglected sign in heart failure patients.

Profuse sweating is a symptom often reported by cardiological patients and could be also an early phenomenon of adaptation or rather cardiac maladaptation in the context of incipient heart failure (HF). By definition, in HF patients the low cardiac output causing reduced renal blood supply and reduced pressure in the arterial baroreceptors activate compensatory mechanisms such as the RAAS and the adrenergic autonomic nervous system. The retention of fluids caused by the decompensation of heart-kidney system could generate a reactive hyperhidrosis and even anticipate an incipient decompensation and might prevent manifest volume overload. Moreover, in HF patients the overactive sympathetic nervous system generates an increase in the reabsorption of fluids in the kidney, on the other hand it generates a signaling to the sweat glands to induce a dispersion of fluids, with loss of sodium and chlorine at the glandular ductal level. Finally sweat gland production physiology during physical activity is also altered in HF patients. This review is focused on sweating and its pathophysiological role in heart failure. Although all the mechanisms underlying this phenomenon are not fully understood, there are interesting connections that might explain this fluid elimination as a wise and sophisticated way to prevent incipient heart failure crisis. Future research could be focused on studying new drugs that selectively would be able to promote fluid elimination by this specific way in patients suffering from heart failure.

Right ventricular endomyocardial biopsy in patients with cardiac magnetic resonance showing left ventricular myocarditis.

AIMS: The aim of this study was to evaluate the sensitivity of right ventricular endomyocardial biopsy (EMB) in myocarditis patients with cardiac magnetic resonance (CMR) and electroanatomical mapping (EAM) showing left ventricular abnormalities. METHODS: We performed right ventricular EMB in 144 consecutive patients (66% men, age 43 ±â€Š15 years) with acute symptoms and CMR-proved diagnosis of left ventricular myocarditis. Right ventricular EMB sensitivity has been evaluated in patients with different localization and extension of abnormal substrate at both CMR and -- when performed -- EAM. Abnormal substrate was defined, respectively, by late gadolinium enhancement (LGE) and low-voltage areas (LVAs). RESULTS: Globally, right ventricular EMB sensitivity was 87.5%. EMB-negative cases had significantly smaller fragment sizes (cumulative area 2.8 ±â€Š1.7 vs. 3.8 ±â€Š1.8 mm2, P = 0.023), and lower LGE surface extension (24.7 ±â€Š14.2 vs. 38.5 ±â€Š20.2%, P = 0.006) and transmurality (32.0 ±â€Š26.1 vs. 49.3 ±â€Š22.6, P = 0.003). Right ventricular EMB sensitivity in patients with LGE involving both right ventricular and interventricular septum (IVS), isolated right ventricular or IVS, and remote left ventricular areas (n = 10, 49 and 67 cases) was 83.3, 84.4 and 90.5%, respectively (P = 0.522). Overall, 34 patients (23.6%) underwent EAM. On the basis of EAM, right ventricular EMB sensitivity was 85.3%: in detail, it was 50.0, 88.2 and 86.7% in patients with both right ventricular and IVS, isolated right ventricular/IVS and distant left ventricular involvement (n = 2, 17 and 15, respectively, P > 0.05). Sample size area was the only factor associated with right ventricular EMB sensitivity (hazard ratio = 1.6/mm2, 95% confidence interval 1.1-2.4, P = 0.013). CONCLUSION: Right ventricular EMB is still an accurate technique to confirm diagnosis in patients with CMR-proved left ventricular myocarditis. In particular, provided there is an adequate sample size, its sensitivity is comparable among patients with heterogeneous LGE or LVA localization.

Cardiac fibrosis: emerging agents in preclinical and clinical development.

INTRODUCTION: Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-ß), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on which research has been currently focusing. AREA COVERED: This review initially discusses those drugs used in clinical practice for their anti-fibrotic properties and later examines emerging pathway-specific agents in preclinical and clinical development [phase I and II-concluded or ongoing trials]. We performed a PubMed, Embase and Google Scholar research including original articles, systematic reviews, ongoing and completed trials using combinations of keywords such as 'myocardial fibrosis', 'reverse remodeling', 'RAAs', 'therapy'. EXPERT OPINION: A variety of preclinical evidences suggest that new drugs and molecules are potentially useful to target cardiac fibrosis and improve left ventricular function, reduce infarct size and scars, delay incident heart failure and cardiac dysfunction in animal models. However, there are very few clinical trials investigating the effect of such drugs in this setting, as well as a lack of new engineered molecules for specific targets.

Immunosuppressive therapy in childhood-onset arrhythmogenic inflammatory cardiomyopathy.

We present, to our knowledge, the first case of immunosuppressive therapy (IST) application in a 12-year-old child with arrhythmogenic inflammatory cardiomyopathy resulting from the overlap between autoimmune myocarditis and primary arrhythmogenic cardiomyopathy. Indication to off-lable IST was compelling, because of recurrent drug-refractory ventricular arrhythmias (VAs). We show that IST was feasible, safe, and effective on multiple clinical endpoints, including symptoms, VA recurrences, and T-troponin release. Remarkably, all diagnostic and therapeutic strategies were worked out by a dedicated multidisciplinary team, including specialized pediatric immunologists.