Light-chain cardiac amyloidosis: a case report of extraordinary sustained pathological response to cyclophosphamide, bortezomib, and dexamethasone combined therapy

Background: Heart involvement represents the most ominous prognostic factor in light-chain amyloidosis (AL), often foreclosing curative therapies such as high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). Heart transplantation (HTx) may be considered before ASCT in rigorously selected cases of advanced AL cardiac amyloidosis (CA). In ASCT-ineligible patients, chemotherapy with cyclophosphamide, bortezomib, and dexamethasone combined (CyBorD) regimen, even at low-dose, is feasible and effective in obtaining hematological and organ response. Case Summary: A previously healthy 50-year-old woman presented with severely symptomatic new-onset heart with preserved ejection fraction, significant cardiac hypertrophy, and an 'apical sparing' pattern. Bone marrow and abdominal fat biopsy revealed AL amyloidosis due to a smouldering micromolecular lambda-type myeloma with severe cardiac involvement, and the patient was judged a good candidate to HTx followed by ASCT. Despite fragile conditions, she tolerated a full course of low-dose combination therapy with bortezomib and was withdrawn from HTx list because of unexpected persistent complete hematologic response and major cardiac improvement. Disease remission was achieved in the long term (>3 years). Discussion: We report a case of exceptional persistent hematologic and cardiac response after CyBorD therapy in a patient with advanced AL-CA who left the transplantation lists (both HTx and ASCT). In ASCT-ineligible patients, chemotherapy with CyBorD regimen, even at low-dose, can lead to durable remission of the disease with excellent cardiac response

Redefining the epidemiology of cardiac amyloidosis. A systematic review and meta-analysis of screening studies

Aims An algorithm for non-invasive diagnosis of amyloid transthyretin cardiac amyloidosis (ATTR-CA) and novel disease-modifying therapies have prompted an active search for CA. We examined the prevalence of CA in different settings based on literature data. Methods and results We performed a systematic search for screening studies on CA, focusing on the prevalence, sex and age distribution in different clinical settings. The prevalence of CA in different settings was as follows: bone scintigraphy for non-cardiac reasons (n = 5 studies), 1% (95% confidence interval [CI] 0%-1%); heart failure with preserved ejection fraction (n = 6), 12% (95% CI 6%-20%); heart failure with reduced or mildly reduced ejection fraction (n = 2), 10% (95% CI 6%-15%); conduction disorders warranting pacemaker implantation (n = 1), 2% (95% CI 0%-4%); surgery for carpal tunnel syndrome (n = 3), 7% (95% CI 5%-10%); hypertrophic cardiomyopathy phenotype (n = 2), 7% (95% CI 5%-9%); severe aortic stenosis (n = 7), 8% (95% CI 5%-13%); autopsy series of 'unselected' elderly individuals (n = 4), 21% (95% CI 7%-39%). The average age of CA patients in the different settings ranged from 74 to 90 years, and the percentage of men from 50% to 100%. Many patients had ATTR-CA, but the average percentage of patients with amyloid light-chain (AL) CA was up to 18%. Conclusions Searching for CA in specific settings allows to identify a relatively high number of cases who may be eligible for treatment if the diagnosis is unequivocal. ATTR-CA accounts for many cases of CA across the different settings, but AL-CA is not infrequent. Median age at diagnosis falls in the eighth or ninth decades, and many patients diagnosed with CA are women

Cardiology of the future: xenotransplantation with porcine heart

The reduced availability of human donor hearts compared with the needs of patients with advanced heart failure refractory to medical therapy has promoted the search for therapeutic alternatives to cardiac allografts. Porcine heart xenotransplantation represents one of the most promising frontiers in this field today. From the first researches in the 1960s to today, the numerous advances achieved in the field of surgical techniques, genetic engineering and immunosuppression have made it possible at the beginning of 2022 to carry out the first swine-to-human heart transplant, attaining a survival of 2 months after surgery. The main intellectual and experimental stages that have marked the history of xenotransplantation, the latest acquisitions in terms of genetic editing, as well as the improvement of immunosuppressive therapy are discussed analytically in this article in order to illustrate the underlying complexity of this therapeutic model

Improving health-related quality of life and reducing suicide in primary care: Can social problem–solving abilities help?

Problem-solving deficits and poor health–related quality of life are associated with suicide risk; yet, little is known about the interrelations between these variables. In 220 primary care patients, we examined the potential mediating role of physical and mental health–related quality of life on the relation between social problem–solving ability and suicidal behavior. Participants completed the Suicidal Behaviors Questionnaire-Revised, Social Problem Solving Inventory-Revised, and Short-Form 36 Health Survey. Utilizing bootstrapped mediation, our hypotheses were partially supported; mediating effects were found for mental health–related quality of life on the relation between social problem-solving and suicidal behavior. Physical health–related quality of life was not a significant mediator. Greater social problem–solving ability is associated with better mental health–related quality of life and, in turn, to less suicidal behavior. Interventions promoting social problem–solving ability may increase quality of life and reduce suicide risk in primary care patients

Linee guida sullo scompenso cardiaco a confronto: AHA 2022 versus ESC 2021

Nell’ultimo decennio la pubblicazione di plurimi trial clinici randomizzati, dedicati allo studio di nuove molecole terapeutiche nell’ambito dello scompenso cardiaco (SC), ha rivoluzionato il trattamento di questa patologia, mettendo a disposizione del cardiologo un ricco armamentario terapeutico. Sacubitril/ valsartan, empagliflozin e dapagliflozin hanno dimostrato di ridurre significativamente il rischio di mortalità/ospedalizzazioni nei pazienti con SC e frazione di eiezione (FE) ≤40%; vericiguat e omecamtiv mecarbil si sono rivelati armi utili nel paziente con recente peggioramento dello SC nonostante terapia medica ottimizzata riducendo ulteriormente il rischio di ospedalizzazioni per SC; empagliflozin ha comprovato la sua efficacia nel ridurre il rischio di ospedalizzazioni per SC anche nei pazienti con FE >40%. Si è così allargato lo spettro di farmaci utili per lo SC in aggiunta a betabloccanti (BB), inibitori dell’enzima di conversione dell’angiotensina (ACEi), antagonisti recettoriali dell’angiotensina (ARB) e antagonisti del recettore dei mineralcorticoidi (MRA), storico caposaldo della terapia medica dello SC con FE ridotta. Innovativi dispositivi impiantabili e nuove evidenze nell’ambito della cardiologia interventistica hanno ripuntualizzato la terapia non farmacologica dello SC. La sfida attuale risiede nel dare ordine e corretta priorità alle varie risorse disponibili. In tal senso la Società Europea di Cardiologia (ESC) e l’American Heart Association (AHA) hanno provveduto a stilare nuove linee guida per il trattamento dello SC al fine di fornire indicazioni pratiche per la gestione di tale patologia alla luce delle nuove evidenze disponibili. Se complessivamente i “take home messages” sono sovrapponibili tra le due linee guida, su alcuni punti non trascurabili le due Società prendono posizione diversa. Questo articolo è volto a sollevare affinità e discordanze tra le due linee guida

Paradoxical Pulmonary Embolism in a Patient with Bilateral Renal Infarction: The Role of Contrast-enhanced Ultrasound Imaging

We present the case of a 52-year-old male who was admitted to the hospital for a bilateral pulmonary embolism. On the 5th day of hospitalization, an acute kidney injury (AKI) occurred. A transesophageal echocardiogram was performed and it demonstrated a large patent foramen ovale with a consistent right-to-left shunt. Contrast-enhanced ultrasound (CEUS) was performed and it demonstrated multiple bilateral renal ischemic areas. CEUS represents a valid alternative to computed tomography or magnetic resonance to confirm the diagnosis of bilateral kidney infarction, especially in patients who experience an AKI

Clinical impact of myocardial fibrosis in severe aortic stenosis

8The pressure overload due to the progressive narrowing of the valve area determines the development of the left ventricular hypertrophy which characterizes aortic stenosis (AS). The onset of myocardial fibrosis marks the inexorable decline of an initially compensatory response towards heart failure. However, myocardial fibrosis does not yet represent a key element in the prognostic and therapeutic framework of AS. In this context, cardiac magnetic resonance imaging plays a major role by highlighting both the focal irreversible fibrotic replacement, using the late gadolinium enhancement (LGE) technique, and the earlier diffuse reversible interstitial fibrosis, using the T1 mapping techniques. For this reason, the presence of myocardial fibrosis would be useful to identify a subgroup of patients at greater risk of events among the subjects with severe AS. Actually, more and more evidences seem to identify the presence of LGE as a powerful prognostic factor to be used to optimize the timing of prosthetic valve replacement. Randomized clinical trials, such as the EVoLVeD trial currently underway, will be needed to better define the importance of myocardial fibrosis assessment in the management of patients with AS.openopenCastrichini, Matteo; Vitrella, Giancarlo; De Luca, Antonio; Altinier, Alessandro; Korcova, Renata; Pagura, Linda; Radesich, Cinzia; Sinagra, GianfrancoCastrichini, Matteo; Vitrella, Giancarlo; De Luca, Antonio; Altinier, Alessandro; Korcova, Renata; Pagura, Linda; Radesich, Cinzia; Sinagra, Gianfranc

Prognostic significance of unexplained left ventricular hypertrophy in patients undergoing carpal tunnel surgery

12Carpal tunnel (CT) syndrome is a recognized red-flag of cardiac amyloidosis (CA) and increased cardiovascular (CV) morbidity. We designed this study to characterize the CV profile of patients with CT syndrome at the time of first surgery and to identify high-risk presentations.openopenPorcari, Aldostefano; Pagura, Linda; Longo, Francesca; Sfriso, Enrico; Barbati, Giulia; Murena, Luigi; Longo, Emiliano; Ramella, Vittorio; Arnež, Zoran Marij; Rapezzi, Claudio; Merlo, Marco; Sinagra, GianfrancoPorcari, Aldostefano; Pagura, Linda; Longo, Francesca; Sfriso, Enrico; Barbati, Giulia; Murena, Luigi; Longo, Emiliano; Ramella, Vittorio; Arnež, Zoran Marij; Rapezzi, Claudio; Merlo, Marco; Sinagra, Gianfranc

Combining New Classes of Drugs for HFrEF: from Trials to Clinical Practice

Pharmacological approach to heart failure with reduced ejection fraction (HFrEF) is evolving, as recently published large randomized clinical trials have implemented the disposal of HFrEF treatments with four new classes of drugs, namely angiotensin receptor/neprilysin inhibitor , sodium-glucose co-transporters 2 inhibitors , soluble guanylate cyclase modulators and myosin activators, which have proved to further improve patients' quality of life and long-term outcomes. As these novel drugs target additional pathways not already intercepted by the guideline-directed medical therapy, integration of them in the management of HFrEF is desirable. This review paper aims to provide an overview of the current evolving concepts of HFrEF therapy joining the most recent evidences and to furnish practical suggestions for the use of these new classes of drugs in clinical practice

Cardiac Tumors: Diagnosis, Prognosis, and Treatment

Cardiac masses frequently present significant diagnostic and therapeutic clinical challenges and encompass a broad set of lesions that can be either neoplastic or non-neoplastic. We sought to provide an overview of cardiac tumors using a cardiac chamber prevalence approach and providing epidemiology, imaging, histopathology, diagnostic workup, treatment, and prognoses of cardiac tumors