European Heart Journal

Eloisa Arbustini, Elijah R Behr, Lucie Carrier, Cornelia van Duijn, Paul Evans, Valentina Favalli, Pim van der Harst, Kristina Hermann Haugaa, Guillaume Jondeau, Stefan KÃ¤Ã¤b, Juan Pablo Kaski, Maryam Kavousi, Bart Loeys, Antonis Pantazis, Yigal Pinto, Heribert Schunkert, Alessandro Di Toro, Thomas Thum, Mario Urtis, Johannes Waltenberger, Perry Elliott

doi : 10.1093/eurheartj/ehab895

European Heart Journal, Volume 43, Issue 20, 21 May 2022, Pages 1901â€“1916

This document describes the contribution of clinical criteria to the interpretation of genetic variants using heritable Mendelian cardiomyopathies as an example. The aim is to assist cardiologists in defining the clinical contribution to a genetic diagnosis and the interpretation of molecular genetic reports. The identification of a genetic variant of unknown or uncertain significance is a limitation of genetic testing, but current guidelines for the interpretation of genetic variants include essential contributions from clinical family screening that can establish a de novo assignment of the variant or its segregation with the phenotype in the family. A partnership between clinicians and patients helps to solve major uncertainties and provides reliable and clinically actionable information.

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Electrical management of heart failure: from pathophysiology to treatment

Frits W Prinzen, Angelo Auricchio, Wilfried Mullens, Cecilia Linde, Jose F Huizar

doi : 10.1093/eurheartj/ehac088

European Heart Journal, Volume 43, Issue 20, 21 May 2022, Pages 1917â€“1927

Electrical disturbances, such as atrial fibrillation (AF), dyssynchrony, tachycardia, and premature ventricular contractions (PVCs), are present in most patients with heart failure (HF). While these disturbances may be the consequence of HF, increasing evidence suggests that they may also cause or aggravate HF. Animal studies show that longer-lasting left bundle branch block, tachycardia, AF, and PVCs lead to functional derangements at the organ, cellular, and molecular level. Conversely, electrical treatment may reverse or mitigate HF. Clinical studies have shown the superiority of atrial and pulmonary vein ablation for rhythm control and AV nodal ablation for rate control in AF patients when compared with medical treatment. Ablation of PVCs can also improve left ventricular function. Cardiac resynchronization therapy (CRT) is an established adjunct therapy currently undergoing several interesting innovations. The current guideline recommendations reflect the safety and efficacy of these ablation therapies and CRT, but currently, these therapies are heavily underutilized. This review focuses on the electrical treatment of HF with reduced ejection fraction (HFrEF). We believe that the team of specialists treating an HF patient should incorporate an electrophysiologist in order to achieve a more widespread use of electrical therapies in the management of HFrEF and should also include individual conditions of the patient, such as body size and gender in therapy fine-tuning.

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Cardiotoxicity from chimeric antigen receptor-T cell therapy for advanced malignancies

Matthias Totzeck, Lars Michel, Yi Lin, Joerg Herrmann, Tienush Rassaf

doi : 10.1093/eurheartj/ehac106

European Heart Journal, Volume 43, Issue 20, 21 May 2022, Pages 1928â€“1940

Chimeric antigen receptor (CAR)-T cell therapy is the next revolutionary advance in cancer therapy. By using ex vivo engineered T cells to specifically target antigens, a targeted immune reaction is induced. Chimeric antigen receptor-T cell therapy is approved for patients suffering from advanced and refractory B cell and plasma cell malignancies and is undergoing testing for various other haematologic and solid malignancies. In the process of triggering an anticancer immune reaction, a systemic inflammatory response can emerge as cytokine release syndrome (CRS). The severity of CRS is highly variable across patients, ranging from mild flu-like symptoms to fulminant hyperinflammatory states with excessive immune activation, associated multiorgan failure and high mortality risk. Cytokine release syndrome is also an important factor for adverse cardiovascular (CV) events. Sinus tachycardia and hypotension are the most common reflections, similar to what is seen with other systemic inflammatory response syndromes. Corrected QT interval prolongation and tachyarrhythmias, including ventricular arrhythmias and atrial fibrillation, also show a close link with CRS. Events of myocardial ischaemia and venous thromboembolism can be provoked during CAR-T cell therapy. Although not as closely related to CRS, changes in cardiac function can be observed to the point of heart failure and cardiogenic shock. This may also be encountered in patients with severe valvular heart disease in the setting of CRS. This review will discuss the pertinent CV risks of the growing field of CAR-T cell therapy for todayâ€™s cardiologists, including incidence, characteristics, and treatment options, and will conclude with an integrated management algorithm.

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Heart failure with preserved ejection fraction in patients with normal natriuretic peptide levels is associated with increased morbidity and mortality

Frederik H Verbrugge, Kazunori Omote, Yogesh N V Reddy, Hidemi Sorimachi, Masaru Obokata, Barry A Borlaug

doi : 10.1093/eurheartj/ehab911

European Heart Journal, Volume 43, Issue 20, 21 May 2022, Pages 1941â€“1951

A substantial proportion of patients with heart failure (HF) with preserved ejection fraction (HFpEF) present with normal natriuretic peptide (NP) levels. The pathophysiology and natural history for this phenotype remain unclear.

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BNP: Biomarker Not Perfect in heart failure with preserved ejection fraction

Sanjiv J Shah

doi : 10.1093/eurheartj/ehac121

European Heart Journal, Volume 43, Issue 20, 21 May 2022, Pages 1952â€“1954

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Bariatric surgery and cardiovascular disease: a systematic review and meta-analysis

Sophie L van Veldhuisen, Thomas M Gorter, Gijs van Woerden, Rudolf A de Boer, Michiel Rienstra, Eric J Hazebroek, Dirk J van Veldhuisen

doi : 10.1093/eurheartj/ehac071

European Heart Journal, Volume 43, Issue 20, 21 May 2022, Pages 1955â€“1969

Obesity is a global health problem, associated with significant morbidity and mortality, often due to cardiovascular (CV) diseases. While bariatric surgery is increasingly performed in patients with obesity and reduces CV risk factors, its effect on CV disease is not established. We conducted a systematic review and meta-analysis to evaluate the effect of bariatric surgery on CV outcomes, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline.

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Metabolic/bariatric surgery protects against cardiovascular disease

Geltrude Mingrone, Lidia Castagneto-Gissey, Stefan R Bornstein

doi : 10.1093/eurheartj/ehac069

European Heart Journal, Volume 43, Issue 20, 21 May 2022, Pages 1970â€“1972

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Cereblon contributes to cardiac dysfunction by degrading Cav1.2Î±

Nammi Park, Jubert Marquez, Trong Kha Pham, Tae Hee Ko, Jae Boum Youm, Min Kim, Seung Hak Choi, Jiyoung Moon, Jessa Flores, Kyung Soo Ko, Byoung Doo Rhee, Ippei Shimizu, Tohru Minamino, Jae Du Ha, Jong Yeon Hwang, Seung Joo Yang, Chul-Seung Park, Hyoung Kyu Kim, Jin Han

doi : 10.1093/eurheartj/ehac072

European Heart Journal, Volume 43, Issue 20, 21 May 2022, Pages 1973â€“1989

Cereblon (CRBN) is a substrate receptor of the E3 ubiquitin ligase complex that was reported to target ion channel proteins. L-type voltage-dependent Ca2+ channel (LTCC) density and dysfunction is a critical player in heart failure with reduced ejection fraction (HFrEF). However, the underlying cellular mechanisms by which CRBN regulates LTCC subtype Cav1.2Î± during cardiac dysfunction remain unclear. Here, we explored the role of CRBN in HFrEF by investigating the direct regulatory role of CRBN in Cav1.2Î± activity and examining how it can serve as a target to address myocardial dysfunction.

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