The golden hour in shock management: do a lot, do it quickly.

Cardiogenic shock can be defined as a state of inadequate organ perfusion linked primarily to cardiac pump dysfunction. The two predominant causes of this condition are acute myocardial infarction and acutely decompensated heart failure (ADHF). In recent years, a significant increase in cases of cardiogenic shock from ADHF has been described. Recent evidence has defined that the factors with the greatest impact on the prognosis in this context are the early clinical assessment, the definition of the aetiology, the timely application of pharmacological therapies, or individualized mechanical supports for the circulation. Haemodynamic monitoring can help in the phenotyping of cardiogenic shock and therefore guide therapeutic choices, especially if implemented with the aid of advanced monitoring tools such as the Swan-Ganz catheter. Finally, the presence of a dedicated shock team in the 'hub' centres is fundamental, which facilitates the choice of the best therapeutic strategy on a case-by-case basis.

Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis.

BACKGROUND: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. METHODS: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. RESULTS: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). CONCLUSIONS: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Symptomatic atrial fibrillation and risk of cardiovascular events: data from the Euro Heart Survey.

AIMS: Atrial fibrillation (AF) is associated with a wide range of clinical presentations. Whether and how AF symptoms can affect prognosis is still unclear. Aims of the present analysis were to investigate potential predictors of symptomatic AF and to determine if symptoms are associated with higher incidence of cardiovascular (CV) events at 1-year follow-up. METHODS AND RESULTS: The Euro Heart Survey on Atrial Fibrillation included 3607 consecutive patients with documented AF and available follow-up regarding symptoms status. Patients found symptomatic at baseline were classified into still symptomatic (SS group; n = 896) and asymptomatic (SA; n = 1556) at 1 year. Similarly, asymptomatic patients at baseline were classified into still asymptomatic (AA group; n = 903) and symptomatic (AS group; n = 252) at 1 year. Demographics, as well as clinical variables and medical treatments, were tested as potential predictors of symptoms persistence/development at 1-year. We also compared CV events between SS and SA groups, and AS and AA groups at 1-year follow-up. Both persistence and development of AF symptoms were associated with an increased risk of CV hospitalization, stroke, heart failure worsening, and thrombo-embolism. AF type, hypothyroidism, chronic heart failure, and chronic obstructive pulmonary disease (COPD), were independently associated with an increased risk of symptomatic status at 1-year follow-up between SS and SA groups. CONCLUSION: Persistence or development of symptoms after medical treatment are associated with an increased risk of CV events during a 1-year follow-up. Type of AF, along with hypothyroidism, COPD and chronic heart failure are significantly associated with symptoms persistence despite medical treatment.

Evolution of Cardiogenic Shock Management and Development of a Multidisciplinary Team-Based Approach: Ten Years Experience of a Single Center.

Background: The management of cardiogenic shock (CS) after ACS has evolved over time, and the development of a multidisciplinary team-based approach has been shown to improve outcomes, although mortality remains high. Methods: All consecutive patients with ACS-CS admitted at our CICU from March 2012 to July 2021 were included in this single-center retrospective study. In 2019, we established a "shock team" consisting of a cardiac intensivist, an interventional cardiologist, an anesthetist, and a cardiac surgeon. The primary outcome was in-hospital mortality. Results: We included 167 patients [males 67%; age 71 (61-80) years] with ischemic CS. The proportion of SCAI shock stages from A to E were 3.6%, 6.6%, 69.4%, 9.6%, and 10.8%, respectively, with a mean baseline serum lactate of 5.2 (3.1-8.8) mmol/L. Sixty-six percent of patients had severe LV dysfunction, and 76.1% needed ≥ 1 inotropic drug. Mechanical cardiac support (MCS) was pursued in 91.1% [65% IABP, 23% Impella CP, 4% VA-ECMO]. From March 2012 to July 2021, we observed a significative temporal trend in mortality reduction from 57% to 29% (OR = 0.90, p = 0.0015). Over time, CS management has changed, with a significant increase in Impella catheter use (p = 0.0005) and a greater use of dobutamine and levosimendan (p = 0.015 and p = 0.0001) as inotropic support. In-hospital mortality varied across SCAI shock stages, and the SCAI E profile was associated with a poor prognosis regardless of patient age (OR 28.50, p = 0.039). Conclusions: The temporal trend mortality reduction in CS patients is multifactorial, and it could be explained by the multidisciplinary care developed over the years.

[The IN-HF Registry: the history and the scientific production for the Italian cardiology community]. / Il programma IN-HF: la storia e la produzione scientifica a favore della comunità cardiologica italiana.

The Italian Network on Congestive Heart Failure (IN-CHF) project, later known as IN-HF Online, was launched in 1995 to provide the Italian cardiology community with a digital tool, standardized across the country, for managing outpatients with heart failure (HF), that enabled the creation of a database for clinical, educational and scientific purposes. During its almost three decades of activity, this observational research program has achieved highly positive scientific results. Indeed, IN-HF fostered professional relationships among individuals working in different centers, established a cultural network for the care of HF patients, periodically updated on the scientific advances, and allowed the assessment of several clinical, epidemiological, and prognostic features. These findings have been published in numerous national and international journals, as summarized in the present overview.

A matter of sex-persistent predictive value of MECKI score prognostic power in men and women with heart failure and reduced ejection fraction: a multicenter study.

Background: A sex-based evaluation of prognosis in heart failure (HF) is lacking. Methods and results: We analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72-7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women). Conclusions: S-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

The chronic heart failure evolutions: Different fates and routes.

AIMS: Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk. METHODS AND RESULTS: From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2-year follow-up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow-up paths, as well as specific end-stages conditions of the disease. Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal (n = 527) and external (n = 777) populations. We analyzed 4876 patients (age = 63 [53-71], male gender n = 3973 (81.5%), NYHA class I-II n = 3576 (73.3%), III-IV n = 1300 (26.7%), LVEF = 33 [25.5-39.9], atrial fibrillation n = 791 (16.2%), peak VO2% pred = 54.8 [43.8-67.2]), with a minimum 2-year follow-up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end-stage points. Clusters survival rate varied from 44% to 100% at 2 years and from 20% to 100% at 5 years, respectively. The event frequency at 5-year follow-up for each study cohort cluster was successfully compared with those in the validation cohorts (R = 0.94 and R = 0.84, P < 0.001, for internal and external cohort, respectively). Finally, we conducted a 5-year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant observed in 22% of cases). CONCLUSIONS: Each HF phenotype has a specific disease progression and prognosis. These findings allow to individualize HF patient evolutions and to tailor assessment.

Cardiac resynchronization therapy improves ejection fraction and cardiac remodelling regardless of patients' age.

AIMS: Cardiac resynchronization therapy (CRT) improves symptoms and reduces mortality in heart failure (HF) patients, but little data exist on the efficacy of CRT in the elderly. The aim of our study is to define CRT-related benefits in terms of left ventricular ejection fraction (LVEF) improvement in two subgroups of patients (<75 and ≥75 years old) and test possible differences between these two groups. METHODS AND RESULTS: Single-centre prospective observational study including 65 patients with optimally treated, advanced HF and indication to CRT. All patients were investigated with clinical evaluation, Minnesota Living with Heart Failure Questionnaire (MLHFQ), 12-lead electrocardiogram, and full echocardiographical study before CRT implant and 3 and 12 months after. Left ventricular ejection fraction showed a time-related improvement in the whole population (+10.6% over 12 months) as well as in each subgroup. The magnitude of LVEF improvement was similar in elderly and non-elderly patients (+13.6 vs. +7.9%; P = ns). Left ventricular diameters, pulmonary artery systolic pressure, New York Heart Association class, MLHFQ score, and QRS width all showed a time-related improvement in the whole population as well as in each subgroup. End-diastolic left ventricular diameter remodelling and QRS width reduction were significantly more pronounced in the elderly, whereas other clinical and instrumental secondary endpoints showed a similar improvement between ≥75 and <75 years old patients. There was no significant difference regarding mortality between elderly and non-elderly patients. CONCLUSION: Cardiac resynchronization therapy is as effective in improving LVEF in elderly as in non-elderly patients. Age alone should not be a determinant to restrict resynchronization therapy in HF patients.

Heart failure patients with improved ejection fraction: Insights from the MECKI score database.

AIMS: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). METHODS AND RESULTS: A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0-47.0] versus 29.7 [24.1-34.5]%, B-type natriuretic peptide 122 [65-296] versus 373 [152-888] pg/ml, haemoglobin 13.5 [12.2-14.6] versus 13.7 [12.5-14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7-89.3] versus 70.4 [54.5-85.3] ml/min, peak oxygen uptake 62.2 [50.7-74.1] versus 52.6 [41.8-64.3]% predicted, minute ventilation-to-carbon dioxide output slope 30.0 [26.9-34.4] versus 32.1 [28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis. CONCLUSIONS: Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

[Atrial fibrillation and heart failure]. / Fibrillazione atriale e scompenso cardiaco.

Atrial fibrillation (AF) and heart failure (HF) are two conditions widespread on the population, especially in elderly people. When AF and HF coexist in the same patient, as frequently happens, they trigger a vicious circle of mutual influence, who dramatically hesitates in lower quality of life and in increased mortality. The relationship between AF and HF is long and vigorously investigated: it is an ever-changing field of knowledge because alongside well known and proven results, especiallythe pathophysiological ones, there are new horizons of research since many aspects are still obscure. Hence, this limit is reflected in the complexity of the combined management of AF and HF in clinical practice. It also explains an ominous prognosis despite significant therapeutic advances. In this review we go over again the well-established knowledge about the pathophysiology binder HF and AF; we provide some epidemiological, clinical and therapeutic informations, we also highlight the new acquisitions, the new research areas and, finally, the still unresolved questions.

Eosinophilic Myocarditis: Characteristics, Treatment, and Outcomes.

BACKGROUND: Eosinophilic myocarditis (EM) is an acute life-threatening inflammatory disease of the heart. Neither large case series nor clinical trials on this specific myocarditis have been reported. OBJECTIVES: Based on a systematic revision of all published histologically proven cases, this study aimed to describe the clinical presentation, treatment, and outcome of EM. METHODS: The study screened 443 manuscripts in MEDLINE and EMBASE on cases of EM published until June 2017. The authors identified 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM. RESULTS: Median age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases (≤16 years of age) accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivity and eosinophilic granulomatosis with polyangiitis, which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic or undefined forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n = 30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n = 40), with the highest occurrence in the hypersensitivity form (36.1%; p = 0.026). CONCLUSIONS: EM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome.

Exercise: a "new drug" for elderly patients with chronic heart failure.

Patients with chronic heart failure (CHF) experience progressive deterioration of functional capacity and quality of life (QoL). This prospective, randomized, controlled trial assesses the effect of exercise training (ET) protocol on functional capacity, rehospitalization, and QoL in CHF patients older than 70 years compared with a control group. A total of 343 elderly patients with stable CHF (age, 76.90±5.67, men, 195, 56.9%) were randomized to ET (TCG, n=170) or usual care (UCG, n=173). The ET protocol involved supervised training sessions for 3 months in the hospital followed by home-telemonitored sessions for 3 months. Assessments, performed at baseline and at 3 and 6 months, included: ECG, resting echocardiography, NT-proBNP, 6-minute walk test (6MWT), Minnesota Living with Heart Failure Questionnaire, and comprehensive geriatric assessment with the InterRAI-HC instrument. As compared to UCG, ET patients at 6 months showed: i) significantly increased 6MWT distance (450±83 vs. 290±97 m, p=0.001); ii) increased ADL scores (5.00±2.49 vs. 6.94±5.66, p=0.037); iii) 40% reduced risk of rehospitalisation (hazard ratio=0.558, 95%CI, 0.326-0.954, p=0.033); and iv) significantly improved perceived QoL (28.6±12.3 vs. 44.5±12.3, p=0.001). In hospital and home-based telemonitored exercise confer significant benefits on the oldest CHF patients, improving functional capacity and subjective QoL and reducing risk of rehospitalisation.

Prognostic implications of mitral regurgitation in patients after cardiac resynchronization therapy.

AIM: Mitral regurgitation (MR) is a common finding in patients with heart failure with debatable effects on prognosis. Reduction in MR is one of the mechanisms by which cardiac resynchronization therapy (CRT) exerts its beneficial effects. We investigated the prognostic impact of baseline MR and MR persistence after CRT on outcomes of treated patients. METHODS AND RESULTS: We prospectively followed 1122 CRT patients (66.4 ± 10.3 years, 78% male) who were stratified according to baseline MR severity as having MR- (degree 0-1; n = 508, 45%) or MR+ (degrees 2-3-4; n = 614, 55%). In 916 patients (82%) with MR severity data available at 1-year follow-up, the annual mortality rate was 3.4 and 6.0 per patient-year in the MR- and MR+ group, respectively, with a 1-year incidence rate ratio (IRR) of 1.76 (P < 0.001). Similar results were observed for cardiovascular mortality (1-year IRR 1.72, P = 0.002). When considering survival according to MR severity after CRT, all-cause and cardiovascular mortality were lower in the improved than in the worsened group (1-year IRR 1.87 and 2.33, respectively; both P < 0.001). Regression analysis showed that absence of MR improvement at follow-up was a significant independent predictor of both all-cause and cardiovascular mortality. CONCLUSIONS: Baseline significant MR and absence of MR improvement after CRT are strongly predictive of less favourable long-term survival.

New anthyarrhythmic drugs for atrial fibrillation.

Atrial fibrillation (AF) is a common arrhythmia associated with increased mortality and morbidity. Different studies have shown no significant difference between rhythm and rate control strategies in terms of mortality. Moreover, the use of antiarrhythmic drugs is afflicted by cardiac and extracardiac toxicity and related costs of hospitalization. Nevertheless, some patients require a rhythm-control strategy and new anti-AF agents are being sought. Only few novel agents showed promising results in term of efficacy and safety. Dronedarone and vernakalant are two of these compounds, respectively introduced for the chronic and acute rhythm control of AF. This article will review pharmacology and clinical evidence on the use of dronedarone and vernakalant and will mention currently investigated new antiarrhythmic drugs.

Intravenous vernakalant for the rapid conversion of recent onset atrial fibrillation: systematic review and meta-analysis.

Atrial fibrillation is the most common cardiac arrhythmia and is associated with increased mortality and morbidity. Conversion to sinus rhythm is usually appropriate in patients with acute, symptomatic atrial fibrillation in order to reduce symptoms and prevent complications. Electrical cardioversion is the most used and widespread technique, but requires deep sedation and a fasting state. Pharmacological alternatives are burdened by a delayed onset of action and potential proarrhythmic effects. Therefore, new therapeutic options are being sought. Among those, vernakalant, showed a good efficacy profile and a short onset of action, but with conflicting evidence regarding potential serious adverse events. This drug profile will summarize the pharmacology behind this new drug and review recent evidence in terms of safety and efficacy.

Feasibility of a cardiologist-only approach to sedation for electrical cardioversion of atrial fibrillation: a randomized, open-blinded, prospective study.

BACKGROUND/OBJECTIVES: Sedation with propofol should be administered by personnel trained in advanced airway management. To overcome this limitation, the use of short acting benzodiazepines by cardiologists spread widely, causing concerns about the safety of this procedure in the absence of anesthesiology assistance. The aim of the study was to compare feasibility of a cardiologist-only approach with an anesthesiologist-assisted sedation protocol during elective direct-current cardioversion (DCC) of persistent atrial fibrillation (AF). METHODS: This prospective, open-blinded, randomized study included 204 patients, which were admitted for scheduled cardioversion of persistent AF, and randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the propofol group underwent DCC with anesthesiologist assistance, while patients in the midazolam group saw the cardiologist as the only responsible for both sedation and DCC. RESULTS: Twenty-three adverse events occurred: 13 in the propofol group and 10 in the midazolam group (p=NS). Most of them were related to bradyarrhythmias and respiratory depressions. There was no need of intubation or other advanced resuscitation techniques in any of these patients. No differences were found regarding procedure tolerability and safety endpoints between the two groups. DCC procedures with anesthesiology support were burdened by higher delay from scheduled time and higher costs. CONCLUSIONS: Sedation with midazolam administered by cardiologist-only appears to be as safe as sedation with propofol and anesthesiologist assistance. Adverse events were few in both groups and easily handled by the cardiologist alone. A cardiologist-only approach to sedation provides less procedural delay, thus being easier to schedule and correlated with fewer costs.

How to Manage a High Defibrillation Threshold in ICD Patients: and Does it Really Matter?

OPINION STATEMENT: In the 30 years since its introduction, implantable cardioverter defibrillator (ICD) hardware and programming has evolved greatly. Coupled with a better understanding of how patient factors and anti-arrhythmic drug therapy affect ICD function, these changes have resulted in a modern ICD system which is highly effective at terminating ventricular arrhythmias. This has led to a marked decrease in the conduct of intraoperative defibrillation testing. Still, clinicians are faced with patients who have had unsuccessful intraoperative defibrillation testing or who have experienced one or more failed clinical shocks for ventricular arrhythmias. Thus, clinicians caring for ICD patients must understand the expected performance of modern ICD systems, understand the issues with intraoperative defibrillation testing, and have a strategy for dealing with patients when their ICD has failed to terminate a clinical or induced ventricular arrhythmia. This review will focus on the clinical approach to such patients, including trouble-shooting and system revision.