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.

An unexpected case of recurrence of pulmonary embolism in a patient recovered from COVID19 in full regimen dose of direct oral anticoagulant drug.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a pandemic affecting all countries in the world. Italy has been particularly afflicted by the health emergency, and since the peak phase has passed, major concern regarding medium to long term complications due to COVID-19 is arising. Little is known in literature regarding thromboembolic complications once healed after COVID-19. CASE PRESENTATION: A 51-year-old patient recovered from COVID-19 pneumonia complicated by pulmonary embolism (PE) came to the hospital for palpitations and chest pain. Although he was on treatment dose of direct oral anticoagulation (DOAC), massive recurrent PE was diagnosed. CONCLUSION: In the early post COVID-19 era, the question remains regarding the efficacy of DOACs in COVID-19 patients.

A 57-year-old man with rapidly progressive pulmonary hypertension.

Pulmonary Tumor Thrombotic Microangiopathy (PTTM) is a rare condition associated with neoplastic disorders, predominantly gastric cancer, leading to pre-capillary Pulmonary Hypertension (PH). The pathologic mechanism involved is a fibrocellular intimal proliferation of small pulmonary vessels sustained by nests of carcinomatous cells lodged in pulmonary vasculature. Clinical presentation is nonspecific, including progressive dyspnea and dry cough. Diagnosis of PTTM is extremely challenging ante-mortem and prognosis is poor. Here we describe the case of a middle-aged man, without known previous cancer history. The clinical course was rapidly unfavorable, with progressive dyspnea and PH associated with hemodynamic instability, eventually culminating in patient's death. PTTM diagnosis was made post-mortem. PTTM should be considered in any patient presenting with unexplained PH, especially if it is rapidly progressive, poorly responsive to standard approaches or there is suspected history of malignancy. A prompt diagnosis of PTTM could help in bringing light into this still under-recognized condition.

Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry.

BACKGROUND: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. METHODS: A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. RESULTS: At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). ß-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation. CONCLUSIONS: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.

Clonal hematopoiesis of indeterminate potential: implications for the cardiologists.

Myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and myelofibrosis, are characterized by somatic gene mutations in bone marrow stem cells, which trigger an inflammatory response influencing the development of associated cardiovascular complications. In recent years, the same mutations were found in individuals with cardiovascular diseases even in the absence of hematological alterations. These genetic events allow the identification of a new entity called 'clonal hematopoiesis of indeterminate potential' (CHIP), as it was uncertain whether it could evolve toward hematological malignancies. CHIP is age-related and, remarkably, myocardial infarction, stroke, and heart failure were frequently reported in these individuals and attributed to systemic chronic inflammation driven by the genetic mutation. We reviewed the connection between clonal hematopoiesis, inflammation, and cardiovascular diseases, with a practical approach to improve clinical practice and highlight the current unmet needs in this area of knowledge.

Long-term prognostic performance of cardiac magnetic resonance imaging markers versus complicated clinical presentation after an acute myocarditis.

BACKGROUND: Identifying markers associated with adverse events after acute myocarditis (AM) is relevant to plan follow-up. We assessed the prognostic performance of previously described cardiac magnetic resonance imaging (CMRI) markers and their combination: septal late gadolinium enhancement (LGE) localization and left ventricular ejection fraction (LVEF) < 50 % on baseline CMRI versus complicated clinical presentation (CCP: the presence of sustained ventricular tachycardia, or LVEF<50 % on the first echocardiogram or fulminant presentation). METHODS: We retrospectively assessed 248 AM patients (median age of 34 years, 87.1 % male) from 6 hospitals with onset of cardiac symptoms<30 days, increased troponin, and CMRI/histology consistent with myocarditis to identify those at risk of major cardiac events (cardiac death, heart transplantation, aborted sudden cardiac death, sustained ventricular tachycardia, or heart failure hospitalization). RESULTS: Thirteen patients (5.2 %) experienced at least one major cardiac event after a median follow-up of 4.7 years with a significant hazard ratio of 35.8 for CCP vs. 9.2 for septal LGE vs. 12.4 for LVEF<50 % on baseline CMRI (p = 0.001). CCP had the best c-index to identify patients with events: 0.836 vs. 0.786 for septal LGE and 0.762 for LVEF<50 %, while the combination of CCP plus LVEF<50 % or septal LGE has the highest c-index of 0.866. All 3 markers had high negative predictive value (NPV) of ≥0.98. CONCLUSIONS: Major cardiac events after an AM are relatively low, and CCP, septal LGE, and LVEF<50 % are significantly associated with events. These markers have especially high NPV to identify patients without events after an AM. These observations can help clinicians to monitor the patients after an AM.

Long-term outcomes of phenoclusters in preclinical heart failure with preserved and mildly reduced ejection fraction.

AIMS: The identification of subjects at higher risk for incident heart failure (HF) with preserved ejection fraction (EF) suitable for more intensive preventive programmes remains challenging. We applied phenomapping to the DAVID-Berg population, comprising subjects with preclinical HF, aiming to refine HF risk stratification. METHODS: The DAVID-Berg study prospectively enrolled 596 asymptomatic outpatients with EF > 40% with hypertension, diabetes mellitus or known cardiovascular disease. In this cohort, we performed an unsupervised cluster analysis on 591 patients, including clinical, laboratory, electrocardiographic and echocardiographic parameters. We tested the association between each cluster and a composite outcome of HF/death. RESULTS: The median age was 70 years, 55.5% were males and the median EF was 61.0%. Phenomapping provided three different clusters. Subjects in Cluster 3 were the oldest and had the highest prevalence of atrial fibrillation, the lowest estimated glomerular filtration rate (eGFR), the highest N-terminal pro-brain natriuretic peptide (NT-proBNP) and the largest left atrium. During a median follow-up of 5.7 years, 13.4% of subjects experienced HF/death events (N = 79). Compared with Clusters 1 and 2, Cluster 3 had the worst prognosis (log-rank test: Cluster 3 vs. 1 P < 0.001; Cluster 3 vs. 2 P = 0.008). Cluster 3 was associated with a risk of HF/death 2.5 times higher than Cluster 1 [adjusted hazard ratio (HR) = 2.46, 95% confidence interval (CI) 1.24-4.90]. CONCLUSIONS: Based on phenomapping, older patients with lower kidney function and worse diastolic function might represent a subset of preclinical HF with EF > 40% who deserve more efforts to prevent clinical HF.

Acute Myocarditis Associated With Desmosomal Gene Variants.

BACKGROUND: The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown. OBJECTIVES: The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV. METHODS: In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up. RESULTS: In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. CONCLUSIONS: Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk.

CArdiac resynchronization in combination with beta blocker treatment in advanced chronic heart failure (CARIBE-HF): the results of the CARIBE-HF study.

OBJECTIVE: Cardiac resynchronization therapy (CRT), combined with optimal medical therapy (OMT), is an established treatment for patients with advanced chronic heart failure (ACHF). In ACHF, carvedilol at the dose used in clinical trials, reduces morbidity and mortality. However, patients often do not tolerate the drug at the targeted dosage. The aim of the CARIBE-HF prospective observational study was to investigate the role of CRT in the implementation of carvedilol therapy in patients with ACHF. METHODS: One hundred and six patients (aged 65 12 [mean +/- SD] years) with ACHF were enrolled and treated with OMT, in which carvedilol was titrated up to the maximal dose (phase 1). Subsequently, patients with left ventricular (LV) ejection fraction < or = 35%, NYHA class III-IV and QRS interval > or =120 msec were assigned to CRT. Both CRT and NO-CRT patients underwent a long-term follow-up of 7 years (1193.98 +/- 924 days), while efforts to up titrate the carvedilol dose were continued during the second phase (471 + 310 days). Phase 1 was completed by 84 patients (79%), and 15 (18%) underwent CRT. The mean carvedilol dose in the CRT group was 19.0 +/- 17.8 mg, against 32.7 +/- 19.1 mg in the remaining 69 patients (P = 0.018). At the end of phase 2, CRT patients presented a significantly greater variation of increasing in the carvedilol dose than NO-CRT patients (+20.0 +/- 19.8 mg vs. -0.3 +/- 20.5 mg; P = 0.015), a greater NYHA class reduction (-0.8 +/- 0.6 vs. -0.2 +/- 0.7; P = 0.011), and a greater increase in LV ejection fraction (10.8 +/- 9 vs. 3.1 +/- 6.1; P = 0.018). CONCLUSIONS: The data from the CARIBE study suggest that, in ACHF, CRT may be effective in enabling the target dose of carvedilol to be reached. The significant improvement seen in LV function was probably due to a synergistic effect of CRT and carvedilol. During the extended follow-up (mean 1193.98 +/- 924 days) the mean dosage of carvedilol in the CRT group was significantly higher (P < 0.02).

Association between sleep disordered breathing, neurocognitive impairment and diastolic function in acute heart failure patients: an insight after the vulnerable phase of the hospitalization.

Sleep disordered breathing (SDB) and neurocognitive impairment (NI) are a typical feature of HF (heart failure), especially with preserved ejection fraction (HFpEF). So far, very few data exist regarding changes in the severity of SDB, the degree of NI, and the diastolic function in acute HF (AHF) patients and during follow up. In a population of 24 AHF patients (12 with reduced ejection fraction-HFrEF- and 12 HFpEF) with SDB a complete echocardiogram, a set of NI tests, and a polysomnography were performed in the acute phase and after 90 days. A control group of 12 non-HF patients hospitalized for other cardiovascular causes was considered. At baseline, SDB were present both in HFpEF and HFrEF, and a consistent reduction of apneic events was observed at follow up. Improvements in diastolic and right ventricular function were documented at three months compared to baseline, both in HFpEF and in HFrEF. Compared to HFrEF patients and controls, HFpEF patients showed lower NI scores at baseline tests, but a more significant improvement at three months follow-up. In AHF patients with SDB the achievement of a better compensation could lead to important beneficial effect not only on echocardiographic variables and nocturnal respiratory profile, but also on NI, especially in HFpEF.