Temporal implementation of a regional referral pathway in transthyretin cardiac amyloidosis: Emilia-Romagna experience.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) is a rare and progressive cardiomyopathy caused by amyloid fibril deposition in myocardial tissue. Diagnostic challenges have historically hampered timely detection. Recent advances in noninvasive diagnostic techniques have facilitated ATTR-CA diagnosis. We aimed to examine the development of a regional network for the diagnosis and management of ATTR-CA and describe a cohort of patients with ATTR-CA, investigate diagnostic pathways and assess clinical outcomes according to diagnosis periods. METHODS: We performed a survey study analyzing answers from 11 cardiology centers and we conducted a retrospective study including patients with ATTR-CA attending a referral center between 1 January 2012 and 31 December 2022, and categorized by the period of diagnosis (2012-2016 and 2017-2022). RESULTS: Over the years, a growing number of patients reached a diagnosis and were treated in the surveyed nonreferral centers of the region. The retrospective study showed a more significant diagnostic delay in the earlier period rather than the later one [13.4 (5-30.2) vs. 10.6 (5.0-17.9) months, P = 0.04]. Patients diagnosed after 2017 showed a greater survival rate than those diagnosed earlier (P = 0.02). In the multivariate analysis, the year of diagnosis from 2017 remained independently associated with mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.28-0.79; P = 0.005]. CONCLUSION: This study emphasized the shift toward noninvasive diagnostic criteria. It revealed a positive impact on patient survival and disease management with the use of disease-modifying therapies and diagnostic developments in more recent years. The findings underscore the importance of disease awareness and networking to reduce diagnostic delays and enhance patient journeys for ATTR-CA.

Diagnostic pathways to wild-type transthyretin amyloid cardiomyopathy: a multicentre network study.

AIM: Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt-CA diagnosis, and their potential association with survival. METHODS AND RESULTS: This was a retrospective study of patients diagnosed with ATTRwt-CA at 17 Italian referral centres for CA. Patients were categorized into different 'pathways' according to the medical reason that triggered the diagnosis of ATTRwt-CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all-cause mortality as endpoint. Overall, 1281 ATTRwt-CA patients were included in the study. The diagnostic pathway leading to ATTRwt-CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III-IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III-IV and some comorbidities but not the HF pathway were independently associated with worse survival. CONCLUSIONS: Half of contemporary ATTRwt-CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself.

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.

Current patterns of beta-blocker prescription in cardiac amyloidosis: an Italian nationwide survey.

AIMS: The use of beta-blocker therapy in cardiac amyloidosis (CA) is debated. We aimed at describing patterns of beta-blocker prescription through a nationwide survey. METHODS AND RESULTS: From 11 referral centres, we retrospectively collected data of CA patients with a first evaluation after 2016 (n = 642). Clinical characteristics at first and last evaluation were collected, with a focus on medical therapy. For patients in whom beta-blocker therapy was started, stopped, or continued between first and last evaluation, the main reason for beta-blocker management was requested. Median age of study population was 77 years; 81% were men. Arterial hypertension was found in 58% of patients, atrial fibrillation (AF) in 57%, and coronary artery disease in 16%. Left ventricular ejection fraction was preserved in 62% of cases, and 74% of patients had advanced diastolic dysfunction. Out of the 250 CA patients on beta-blockers at last evaluation, 215 (33%) were already taking this therapy at first evaluation, while 35 (5%) were started it, in both cases primarily because of high-rate AF. One-hundred-nineteen patients (19%) who were on beta-blocker at first evaluation had this therapy withdrawn, mainly because of intolerance in the presence of heart failure with advanced diastolic dysfunction. The remaining 273 patients (43%) had never received beta-blocker therapy. Beta-blockers usage was similar between CA aetiologies. Patients taking vs. not taking beta-blockers differed only for a greater prevalence of arterial hypertension, coronary artery disease, AF, and non-restrictive filling pattern (P < 0.01 for all) in the former group. CONCLUSIONS: Beta-blockers prescription is not infrequent in CA. Such therapy may be tolerated in the presence of co-morbidities for which beta-blockers are routinely used and in the absence of advanced diastolic dysfunction.

[A practical approach to the diagnosis of cardiomyopathy: a roadmap from the phenotype]. / Un approccio pratico alla diagnosi di cardiomiopatia: una roadmap a partire dal fenotipo.

Cardiomyopathies are a heterogeneous group of cardiac diseases for which diagnosis and treatment are not always simple. The diagnosis of cardiomyopathy, in particular the etiology, comes from an integration between symptoms and results collected by several instrumental exams. The brain storming for the diagnosis includes also the identification of the "red flags", i.e. the pathognomonic features for each etiology that can drive the choice of appropriate diagnostic tests and therapy. In this review, we provide a step by step approach in order to help cardiologists, not specifically dedicated to cardiomyopathies, to draw the diagnosis, therapy and follow-up. This approach will be accompanied by the consultation of other specialists to discuss together the results of the exams performed and to deepen extracardiac signs and symptoms.

Cardiac myxoma presenting with sensory neuropathy.

A 51-year-old man was admitted for burning dysesthesias over the soles. Neurologic examination showed a pansensory loss over both feet associated with weakness of toes dorsiflexion. Motor conduction study of the sural nerve showed a significant reduction of nerve conduction velocity (21.4 m/s) suggesting a demyelinating neuropathy. In the following days he was referred to the cardiologist because of the sudden onset of a rapid atrial tachycardia, which was terminated by adenosine. Echocardiography showed a left atrial mass arising from the atrial septum consistent with the diagnosis of cardiac myxoma. The patient underwent cardiac surgery to remove the tumor, which was confirmed a myxoma by pathology. In the days following cardiac mass removal, neurological symptoms progressively disappeared in the absence of anti-inflammatory and steroid therapy and control motor conduction study showed complete normalization of nerve conduction velocity (54.5 m/s). Peripheral demyelinating neuropathy represented the first clinical presentation of cardiac myxoma in our patient and should be included among the possible paraneoplastic manifestations of this cardiac tumor.

High prevalence of myocarditis mimicking arrhythmogenic right ventricular cardiomyopathy differential diagnosis by electroanatomic mapping-guided endomyocardial biopsy.

OBJECTIVES: We evaluated the diagnostic contribution and the therapeutic and prognostic implications of 3-dimensional electroanatomic mapping (EAM)-guided endomyocardial biopsy (EMB) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: ARVC is a frequent cause of life-threatening ventricular arrhythmias and sudden death in young people. The value of current diagnostic criteria and the role of imaging techniques and EMB are still debated. METHODS: We studied 30 consecutive patients (17 male, mean age 43 +/- 17 years) with a noninvasive diagnosis of ARVC according to current criteria. All patients underwent 3-dimensional EAM-guided EMB. RESULTS: Twenty-nine (97%) of 30 patients presented an abnormal voltage map. Histology and immunohistochemistry confirmed the diagnosis of ARVC in 15 patients, and showed active myocarditis according to Dallas criteria in the remaining 15 patients. Patients with ARVC were not distinguishable on the basis of clinical features, presence, and severity of structural and functional right ventricular abnormalities and 3-dimensional EAM findings. On the basis of clinical and histological features, a cardioverter-defibrillator was implanted in 13 patients with biopsy-proven ARVC and in 1 patient only with myocarditis. At a mean follow-up of 21 +/- 8 months, 7 (47%) patients with ARVC experienced a recurrence of symptomatic sustained ventricular arrhythmias with appropriate defibrillator intervention in all cases. All patients with myocarditis remained asymptomatic and free from arrhythmic events. CONCLUSIONS: Right ventricular myocarditis frequently mimics ARVC. Three-dimensional EAM-guided EMB is a safe and effective tool in differential diagnosis and in the selection of the most appropriate therapeutic strategy.

[Recent advances in atherothrombotic diseases]. / Recenti progressi in tema di aterotrombosi.

New concepts in the field of atherothrombosis include the human potential to repair and regenerate areas of vascular damage through endogenous growth factors, and the identification of uncommon arterial thrombophilias that promote atherothrombosis. The endogenous factors erythropoietin and insulin-like growth factor-1 are emerging as robust opponents of the vascular and hemostatic alterations that occur in atherothrombosis. Both factors activate the intracellular Akt pathway and the biosynthesis of constitutive nitric oxide, with anti-apoptotic, insulin-sensitizing, vasodilator, anti-inflammatory, antioxidant and antiplatelet effects, all of which oppose arterial degeneration and occlusion. Additionally, erythropoietin and insulin-like growth factor-1 induce the mobilization of stem cells that can differentiate and repair areas of vascular damage thereby halting the progression towards established disease. In selected patients with an arterial thrombotic event, we believe it is justified to search for an uncommon acquired or inherited thrombophilic condition in the presence of at least one of the following: young age, recurrent events, lack of traditional metabolic or acquired vascular risk factors, and no significant artery stenoses at angiography. In these groups of patients, and in those with a marked family history of thrombosis, the prevalence of several functional polymorphisms of genes involved in the hemostatic system is significantly higher compared with controls. Acquired thrombophilias that should be searched for include the antiphospholipid syndrome, systemic lupus erythematosus, and myeloproliferative disorders.