Publications by authors named "Iacopo Olivotto"

326 Publications

Myocardial infarction with non-obstructive coronary arteries in hypertrophic cardiomyopathy vs Fabry disease.

Int J Cardiol 2022 Aug 2. Epub 2022 Aug 2.

Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy.

Background: Little is known about prevalence and predictors of myocardial infarction with non-obstructive coronary arteries (MINOCA) in Fabry disease (FD) and hypertrophic cardiomyopathy (HCM). We assessed and compared the prevalence and predictors of MINOCA in a large cohort of HCM and FD patients.

Methods: In this multicenter, retrospective study we enrolled 2870 adult patients with HCM and 267 with FD. The only exclusion criterion was documented obstructive coronary artery disease. MINOCA was defined according to guidelines. For each patient we collected clinical, ECG and echocardiographic data recorded at initial evaluation.

Results: Overall, 36 patients had MINOCA during a follow-up period of 4.5 ± 11.2 years, MINOCA occurred in 16 patients with HCM (0.5%) and 20 patients with FD (7.5%; p < 0.001). The difference between the 2 groups was highly significant, also after adjustment for the main clinical, ECG and echocardiographic variables (OR 6.12;95%CI:2.80-13.3;p < 0.001). In the FD population MINOCA occurred in 17 out of 96 patients with left ventricle hypertrophy (LVH, 17.7%) and in 3 out of 171 patients without LVH (1.7%; OR 12.0;95%CI 3.43-42.3;p < 0.001). At multivariable analysis, voltage criteria for LVH at ECG (OR 7.3;95%CI 1.93-27.7;p = 0.003) and maximal LV wall thickness at echocardiography (OR 1.15; 95%CI 1.05-1.27;p = 0.002) maintained an independent association with MINOCA. No major significant differences were found in clinical, ECG and echocardiographic findings between HCM patients with or without MINOCA.

Conclusions: MINOCA was rare in HCM patients, and 6-fold more frequent in FD patients. MINOCA may be considered a red flag for FD and aid in the differential diagnosis from HCM.
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http://dx.doi.org/10.1016/j.ijcard.2022.07.046DOI Listing
August 2022

Paradoxical prolongation of QT interval during exercise in patients with hypertrophic cardiomyopathy: cellular mechanisms and implications for diastolic function.

Eur Heart J Open 2022 May 10;2(3):oeac034. Epub 2022 May 10.

Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Firenze, Italy.

Aims: Ventricular cardiomyocytes from hypertrophic cardiomyopathy (HCM) patient hearts show prolonged action potential duration (APD), impaired intracellular Ca homeostasis and abnormal electrical response to beta -adrenergic stimulation. We sought to determine whether this behaviour is associated with abnormal changes of repolarization during exercise and worsening of diastolic function, ultimately explaining the intolerance to exercise experienced by some patients without obstruction.

Methods And Results: Non-obstructive HCM patients (178) and control subjects (81) underwent standard exercise testing, including exercise echocardiography. Ventricular myocytes were isolated from myocardial samples of 23 HCM and eight non-failing non-hypertrophic surgical patients. The APD shortening in response to high frequencies was maintained in HCM myocytes, while β-adrenergic stimulation unexpectedly prolonged APDs, ultimately leading to a lesser shortening of APDs in response to exercise. In HCM vs. control subjects, we observed a lesser shortening of QT interval at peak exercise (QTc: +27 ± 52 ms in HCM, -4 ± 50 ms in controls,  < 0.0001). In patients showing a marked QTc prolongation (>30 ms), the excessive shortening of the electrical diastolic period was linked with a limited increase of heart-rate and deterioration of diastolic function at peak effort.

Conclusions: Abnormal balance of Ca- and K-currents in HCM cardiomyocytes determines insufficient APD and Ca-transient shortening with exercise. In HCM patients, exercise-induced QTc prolongation was associated with impaired diastolic reserve, contributing to the reduced exercise tolerance. Our results support the idea that severe electrical cardiomyocyte abnormalities underlie exercise intolerance in a subgroup of HCM patients without obstruction.
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http://dx.doi.org/10.1093/ehjopen/oeac034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242073PMC
May 2022

[Clinical pathway on pediatric cardiomyopathies: a genetic testing strategy proposed by the Italian Society of Pediatric Cardiology].

G Ital Cardiol (Rome) 2022 Jul;23(7):505-515

S.O.C. Cardiologia Pediatrica, Azienda Ospedaliero-Universitaria Meyer, Firenze.

Pediatric cardiomyopathies are rare diseases, heterogeneous in clinical presentation, etiology and prognosis. Etiological diagnosis, where genetic analysis plays a key role, is of fundamental importance for defining diagnostic and therapeutic pathways. Furthermore, the identification of the genetic substrate represents a prerequisite for cascade screening in the proband's family members and to allow conscious reproductive choices. To date, genetic testing is performed with the analysis of gene panels (targeted panels) or with the study of the entire exome (whole exome sequencing) using next generation sequencing (NGS) technology. The great genetic heterogeneity and the temporal variability of the clinical manifestations lead to unique problems for pediatric cardiomyopathies, distinct from those of the adult, such as the possible indications for access to the test, the type of test to be used (exome or panel of genes), the importance of analyzing parents, especially in cases with neonatal onset; moreover, the correct execution of bioinformatics analysis and the interpretation of NGS data play a crucial role in the impact of the results on clinical management.
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http://dx.doi.org/10.1714/3831.38168DOI Listing
July 2022

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator.

Eur Heart J 2022 Jun 29. Epub 2022 Jun 29.

National Reference Center for Inherited Arrhythmias of Lyon, Louis Pradel Cardiovascular Hospital, Hospices Civils de Lyon, Lyon, France.

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus.

Methods And Results: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%.

Conclusion: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC.
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http://dx.doi.org/10.1093/eurheartj/ehac289DOI Listing
June 2022

Sudden death in young athletes: Is it preventable?

Eur J Intern Med 2022 Jun 16. Epub 2022 Jun 16.

Sport Medicine Unit, Careggi University Hospital, University of Florence, Largo Brambilla 3, Florence 50134, Italy.

Sudden death in young athletes is a rare but always dramatic condition. Unlike all other rare diseases, the estimate of its real incidence is made complex not only because of the uncertain number of correctly identified cases (numerator) but also because of the uncertain estimation of the real number of the reference population, the athletes (denominator). New elements of complexity are also emerging with regard to prevention. The current two pillars of prevention are pre-participation screening (proactive strategy) and promoting use / access to the automated external defibrillator (reactive strategy). The standardization of procedures implemented over the past two decades for pre-participation screening can now allow us to assess the impact of this approach. The result is complex to evaluate. While screening may allow the identification of conditions potentially associated with SDA, and therefore the adoption of specific treatments, in about 0.4% of screened subjects, a single study investigated the yield in terms of mortality showing a positive predictive value of 4.7% with 25% sensitivity. Conversely, the reactive strategy appears considerably effective, due to the widespread use of the automated external defibrillators in sports facilities, calling for a homogeneous implementation worldwide. On a broader perspective, the vast attention devoted to SDA prevention in the world of sports represents a major driver for transfer of a reactive prevention strategy to the general population.
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http://dx.doi.org/10.1016/j.ejim.2022.06.009DOI Listing
June 2022

Pharmacological Management of Hypertrophic Cardiomyopathy: From Bench to Bedside.

Drugs 2022 Jun 13;82(8):889-912. Epub 2022 Jun 13.

Department NeuroFarBa, University of Florence, Florence, Italy.

Hypertrophic cardiomyopathy (HCM), the most common inherited heart disease, is still orphan of a specific drug treatment. The erroneous consideration of HCM as a rare disease has hampered the design and conduct of large, randomized trials in the last 50 years, and most of the indications in the current guidelines are derived from small non-randomized studies, case series, or simply from the consensus of experts. Guideline-directed therapy of HCM includes non-selective drugs such as disopyramide, non-dihydropyridine calcium channel blockers, or β-adrenergic receptor blockers, mainly used in patients with symptomatic obstruction of the outflow tract. Following promising preclinical studies, several drugs acting on potential HCM-specific targets were tested in patients. Despite the huge efforts, none of these studies was able to change clinical practice for HCM patients, because tested drugs were proven to be scarcely effective or hardly tolerated in patients. However, novel compounds have been developed in recent years specifically for HCM, addressing myocardial hypercontractility and altered energetics in a direct manner, through allosteric inhibition of myosin. In this paper, we will critically review the use of different classes of drugs in HCM patients, starting from "old" established agents up to novel selective drugs that have been recently trialed in patients.
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http://dx.doi.org/10.1007/s40265-022-01728-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209358PMC
June 2022

Development of the Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ): A New Patient-Reported Outcome (PRO) Instrument.

Pharmacoecon Open 2022 Jul 2;6(4):563-574. Epub 2022 Jun 2.

Cardiomyopathy Unit, Careggi University Hospital, University of Florence, Florence, Italy.

Background: Currently, there is no patient-reported outcome (PRO) instrument specifically designed to evaluate hypertrophic cardiomyopathy (HCM).

Objective: We present the development and psychometric validation of a novel PRO measure, the HCM Symptom Questionnaire version 1.0 (HCMSQv1.0).

Methods: Cognitive debriefing interviews and a card-sorting task were conducted in 33 patients with HCM to support development of the HCMSQv1.0, showing the scale to be interpretable and relevant to patients' experiences. Baseline blinded data from two trials (EXPLORER-HCM and MAVERICK-HCM) were pooled (N = 299) to develop the scoring algorithm of HCMSQv1.0. Measurement properties were examined, followed by a meaningful-change analysis to interpret scores. Rasch modeling, mixed-model repeated measures, exploratory factor analysis, confirmatory factor analysis, and missing-data simulation analysis informed the number of domains and the items in each domain.

Results: The scoring algorithm for HCMSQv1.0 consists of four domains: shortness of breath, tiredness, cardiovascular symptoms, and syncope; plus a total score, with higher scores indicating more severe symptoms. Item characteristics, internal consistency, test-retest reliability, construct validity, and responsiveness were acceptable. A clinically meaningful responder definition of 1-2 points on the HCMSQv1.0 score for shortness of breath and total score, and approximately 1 point on the tiredness and cardiovascular symptom scores, was calculated based on distribution- and anchor-based methods.

Conclusion: Our findings support the HCMSQv1.0 as a fit-for-purpose PRO instrument for assessing treatment benefit in patients with HCM. Studies in larger patient populations are ongoing to confirm responder definition and scoring approaches encompassing key HCM symptoms.
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http://dx.doi.org/10.1007/s41669-022-00335-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283619PMC
July 2022

Orphan Drug Use in Patients With Rare Diseases: A Population-Based Cohort Study.

Front Pharmacol 2022 16;13:869842. Epub 2022 May 16.

Unit of Epidemiology of Rare Diseases and Congenital Anomalies, Institute of Clinical Physiology, National Research Council, Pisa, Italy.

Orphan drugs are used for the diagnosis, prevention and treatment of rare diseases that, in the European Union, are defined as disorders affecting no more than 5 persons in 10,000. So far, a total of around 800 orphan medicinal products have been approved by the European Medicines Agency, however the utilization profile of orphan drugs has yet to be explored. This study aimed at assessing the utilization profile of orphan drugs authorized for marketing by the Italian Medicines Agency using population-based data. A total of 21 orphan drugs used in outpatient settings, approved in the European Union before or during the 2008-2018 period and involving 15 rare diseases, were included in the study. The monitored population included patients with one of the conditions surveilled by the population-based Tuscany Registry of Rare Diseases and diagnosed between 2000-2018. A multi-database approach was applied, by linking data from the registry with information collected in drug prescriptions databases. The prevalence and intensity of use were estimated for the selected orphan drugs and other non-orphan medications, used to treat the same rare disease and for which a change in the prevalence of use was hypothesized after authorization of the orphan drug. For some diseases (acquired aplastic anemia, tuberous sclerosis complex, most metabolic diseases) a low prevalence of orphan drugs use was observed (range between 1.1-12.5%). Conversely, orphan drugs were frequently used in hemophilia B, Wilson disease and idiopathic pulmonary fibrosis (maximum of 78.3, 47.6 and 41.8%, respectively). For hemophilia B and Leber's hereditary optic neuropathy, there are currently no other medications used in clinical practice in addition to orphan drugs. Six orphan drugs were used for the treatment of pulmonary arterial hypertension, appearing the elective therapy for this disease, albeit with different utilization profiles (range of prevalence 1.7-55.6%). To the best of our knowledge, this is the first study investigating the utilization profile of orphan drugs prescribed in a defined geographical area, and providing relevant information to monitor over time potential changes in the prevalence of these medications as well as in the health care decision making.
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http://dx.doi.org/10.3389/fphar.2022.869842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148958PMC
May 2022

Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy.

J Am Coll Cardiol 2022 05;79(20):1986-1997

University Hospital of Wales, Cardiff, United Kingdom.

Background: Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized.

Objectives: The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years.

Methods: Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years.

Results: At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age.

Conclusions: Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.
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http://dx.doi.org/10.1016/j.jacc.2022.03.347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125690PMC
May 2022

Sarcomere protein modulation: The new frontier in cardiovascular medicine and beyond.

Eur J Intern Med 2022 Aug 6;102:1-7. Epub 2022 May 6.

Azienda Ospedaliera Universitaria Careggi and University of Florence, Florence, Italy. Electronic address:

Over the past decade, the constant progress in science and technologies has provided innovative drug molecules that address specific disease mechanisms thus opening the era of drugs targeting the underlying pathophysiology of the disease. In this scenario, a new paradigm of modulation has emerged, following the development of small molecules capable of interfering with sarcomere contractile proteins. Potential applications include heart muscle disease and various forms of heart failure, although promising targets also include conditions affecting the skeletal muscle, such as degenerative neuromuscular diseases. In cardiac patients, a cardiac myosin stimulator, omecamtiv mecarbil, has shown efficacy in heart failure with reduced systolic function, lowering heart failure related events or cardiovascular death, while two inhibitors, mavacamten and aficamten, in randomized trials targeting hypertrophic cardiomyopathy, have been shown to reduce hypercontractility and left ventricular outflow obstruction improving functional capacity. Based on years of intensive basic and translational research, these agents are the prototypes of active pipelines promising to deliver an array of molecules in the near future. We here review the available evidence and future perspectives of myosin modulation in cardiovascular medicine.
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http://dx.doi.org/10.1016/j.ejim.2022.04.020DOI Listing
August 2022

Genotype-Driven Pathogenesis of Atrial Fibrillation in Hypertrophic Cardiomyopathy: The Case of Different Mutations.

Front Physiol 2022 19;13:864547. Epub 2022 Apr 19.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Atrial dilation and atrial fibrillation (AF) are common in Hypertrophic CardioMyopathy (HCM) patients and associated with a worsening of prognosis. The pathogenesis of atrial myopathy in HCM remains poorly investigated and no specific association with genotype has been identified. By re-analysis of our cohort of thin-filament HCM patients (Coppini et al. 2014) AF was identified in 10% of patients with sporadic mutations in the cardiac Troponin T gene (), while AF occurrence was much higher (25-75%) in patients carrying specific "hot-spot" mutations. To determine the molecular basis of arrhythmia occurrence, two HCM mouse models expressing human variants (a "hot-spot" one, R92Q, and a "sporadic" one, E163R) were selected according to the different pathophysiological pathways previously demonstrated in ventricular tissue. Echocardiography studies showed a significant left atrial dilation in both models, but more pronounced in the R92Q. In E163R atrial trabeculae, in line with what previously observed in ventricular preparations, the energy cost of tension generation was markedly increased. However, no changes of twitch amplitude and kinetics were observed, and there was no atrial arrhythmic propensity. R92Q atrial trabeculae, instead, displayed normal ATP consumption but markedly increased myofilament calcium sensitivity, as previously observed in ventricular preparations. This was associated with reduced inotropic reserve and slower kinetics of twitch contractions and, importantly, with an increased occurrence of spontaneous beats and triggered contractions that represent an intrinsic arrhythmogenic mechanism promoting AF. The association of specific mutations with AF occurrence depends on the mutation-driven pathomechanism (i.e., increased atrial myofilament calcium sensitivity rather than increased myofilament tension cost) and may influence the individual response to treatment.
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http://dx.doi.org/10.3389/fphys.2022.864547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062294PMC
April 2022

Cardiac Myosin Inhibitors as a Novel Treatment Option for Obstructive Hypertrophic Cardiomyopathy: Addressing the Core of the Matter.

J Am Heart Assoc 2022 05 3;11(9):e024656. Epub 2022 May 3.

Cardiomyopathy Unit Department of Experimental and Clinical Medicine University of Florence Italy.

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http://dx.doi.org/10.1161/JAHA.121.024656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238628PMC
May 2022

Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy.

Circ Arrhythm Electrophysiol 2022 05 2;15(5):e010075. Epub 2022 May 2.

Leeds General Infirmary, United Kingdom (E.B.).

Background: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort.

Methods: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids).

Results: MLVWT score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT score, peaking at score +23. The presence of coexisting risk factors had a summative effect on risk.

Conclusions: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.
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http://dx.doi.org/10.1161/CIRCEP.121.010075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612749PMC
May 2022

Sex-Related Differences in Genetic Cardiomyopathies.

J Am Heart Assoc 2022 05 26;11(9):e024947. Epub 2022 Apr 26.

Cardiomyopathy Unit Careggi University Hospital Florence Italy.

Cardiomyopathies are a heterogeneous collection of diseases that have in common primary functional and structural abnormalities of the heart muscle, often genetically determined. The most effective categorization of cardiomyopathies is based on the presenting phenotype, with hypertrophic, dilated, arrhythmogenic, and restrictive cardiomyopathy as the prototypes. Sex modulates the prevalence, morpho-functional manifestations and clinical course of cardiomyopathies. Aspects as diverse as ion channel expression and left ventricular remodeling differ in male and female patients with myocardial disease, although the reasons for this are poorly understood. Moreover, clinical differences may also result from complex societal/environmental discrepancies between sexes that may disadvantage women. This review provides a state-of-the-art appraisal of the influence of sex on cardiomyopathies, highlighting the many gaps in knowledge and open research questions.
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http://dx.doi.org/10.1161/JAHA.121.024947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238595PMC
May 2022

Metabolomics Fingerprint Predicts Risk of Death in Dilated Cardiomyopathy and Heart Failure.

Front Cardiovasc Med 2022 7;9:851905. Epub 2022 Apr 7.

Department of Chemistry "Ugo Schiff", Magnetic Resonance Center (CERM), University of Florence, Sesto Fiorentino, Italy.

Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Metabolomics may help refine risk assessment and potentially guide HF management, but dedicated studies are few. This study aims at stratifying the long-term risk of death in a cohort of patients affected by HF due to dilated cardiomyopathy (DCM) using serum metabolomics nuclear magnetic resonance (NMR) spectroscopy.

Methods: A cohort of 106 patients with HF due to DCM, diagnosed and monitored between 1982 and 2011, were consecutively enrolled between 2010 and 2012, and a serum sample was collected from each participant. Each patient underwent half-yearly clinical assessments, and survival status at the last follow-up visit in 2019 was recorded. The NMR serum metabolomic profiles were retrospectively analyzed to evaluate the patient's risk of death. Overall, 26 patients died during the 8-years of the study.

Results: The metabolomic fingerprint at enrollment was powerful in discriminating patients who died (HR 5.71, = 0.00002), even when adjusted for potential covariates. The outcome prediction of metabolomics surpassed that of N-terminal pro b-type natriuretic peptide (NT-proBNP) (HR 2.97, = 0.005). Metabolomic fingerprinting was able to sub-stratify the risk of death in patients with both preserved/mid-range and reduced ejection fraction [hazard ratio (HR) 3.46, = 0.03; HR 6.01, = 0.004, respectively]. Metabolomics and left ventricular ejection fraction (LVEF), combined in a score, proved to be synergistic in predicting survival (HR 8.09, = 0.0000004).

Conclusions: Metabolomic analysis NMR enables fast and reproducible characterization of the serum metabolic fingerprint associated with poor prognosis in the HF setting. Our data suggest the importance of integrating several risk parameters to early identify HF patients at high-risk of poor outcomes.
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http://dx.doi.org/10.3389/fcvm.2022.851905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021397PMC
April 2022

Clinical presentations leading to arrhythmogenic left ventricular cardiomyopathy.

Open Heart 2022 04;9(1)

Cardiology Unit, St. Orsola Hospital, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

Objectives: To describe a cohort of patients with arrhythmogenic left ventricular cardiomyopathy (ALVC), focusing on the spectrum of the clinical presentations.

Methods: Patients were retrospectively evaluated between January 2012 and June 2020. Diagnosis was based on (1) ≥3 contiguous segments with subepicardial/midwall late gadolinium enhancement in the left ventricle (LV) at cardiac magnetic resonance a likely pathogenic/pathogenic arrhythmogenic cardiomyopathy (AC) associated genetic mutation familial history of AC red flags for ALVC (ie, negative T waves in V4-6/aVL, low voltages in limb leads, right bundle branch block like ventricular tachycardia) or (2) pathology examination of explanted hearts or autoptic cases suffering sudden cardiac death (SCD). Significant right ventricular involvement was an exclusion criterion.

Results: Fifty-two patients (63% males, age 45 years (31-53)) composed the study cohort. Twenty-one (41%) had normal echocardiogram, 13 (25%) a hypokinetic non-dilated cardiomyopathy (HNDC) and 17 (33%) a dilated cardiomyopathy (DCM). Of 47 tested patients, 29 (62%) were carriers of a pathogenic/likely pathogenic DNA variant. Clinical contexts leading to diagnosis were SCD in 3 (6%), ventricular arrhythmias in 15 (29%), chest pain in 8 (15%), heart failure in 6 (12%) and familial screening in 20 (38%). Thirty patients (57%) had previously received a diagnosis other than ALVC with a diagnostic delay of 6 years (IQR 1-7).

Conclusions: ALVC is hidden in different clinical scenarios with a phenotypic spectrum ranging from normal LV to HNDC and DCM. Ventricular arrhythmias, chest pain, heart failure and SCD are the main clinical presentations, being familial screening essential for the affected relatives' identification.
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http://dx.doi.org/10.1136/openhrt-2021-001914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9021777PMC
April 2022

Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the AC-TIVE study, an Italian nationwide survey.

Eur J Heart Fail 2022 Apr 13. Epub 2022 Apr 13.

University Cardiology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.

Aim: To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions.

Methods And Results: This is an Italian prospective multicentre study, involving a clinical and instrumental work-up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non-dilated left ventricles with preserved ejection fraction). The study was registered at ClinicalTrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%-35%). Transthyretin-related AC (ATTR-AC) was diagnosed in 51 and light chain-related AC (AL-AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%.

Conclusion: In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy.
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http://dx.doi.org/10.1002/ejhf.2504DOI Listing
April 2022

Diagnosis and Management of Rare Cardiomyopathies in Adult and Paediatric Patients. A Position Paper of the Italian Society of Cardiology (SIC) and Italian Society of Paediatric Cardiology (SICP).

Int J Cardiol 2022 06 30;357:55-71. Epub 2022 Mar 30.

Department of Clinical and Molecular Medicine, Sapienza University of Rome, Division of Cardiology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy.

Cardiomyopathies (CMPs) are myocardial diseases in which the heart muscle is structurally and functionally abnormal in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality. Thought for a long time to be rare diseases, it is now clear that most of the CMPs can be easily observed in clinical practice. However, there is a group of specific heart muscle diseases that are rare in nature whose clinical/echocardiographic phenotypes resemble those of the four classical morphological subgroups of hypertrophic, dilated, restrictive, arrhythmogenic CMPs. These rare CMPs, often but not solely diagnosed in infants and paediatric patients, should be more properly labelled as specific CMPs. Emerging consensus exists that these conditions require tailored investigation and management. Indeed, an appropriate understanding of these conditions is mandatory for early treatment and counselling. At present, however, the multisystemic and heterogeneous presentation of these entities is a challenge for clinicians, and time delay in diagnosis is a significant concern. The aim of this paper is to define practical recommendations for diagnosis and management of the rare CMPs in paediatric or adult age. A modified Delphi method was adopted to grade the recommendations proposed by each member of the writing committee.
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http://dx.doi.org/10.1016/j.ijcard.2022.03.050DOI Listing
June 2022

[From loss to prevention: lessons to be learned from juvenile sudden death].

G Ital Cardiol (Rome) 2022 Mar;23(3):211-213

Unit Cardiomiopatie, Azienda Ospedaliera Universitaria Careggi, Firenze.

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http://dx.doi.org/10.1714/3751.37340DOI Listing
March 2022

Syncope in hypertrophic cardiomyopathy (part I): An updated systematic review and meta-analysis.

Int J Cardiol 2022 06 15;357:88-94. Epub 2022 Mar 15.

Department of Cardiology, IRCCS Istituto Auxologico Italiano, Department of Cardiovascular, Neural and Metabolic Sciences, Ospedale San Luca, Milan, Italy. Electronic address:

Aims: To describe the proportion of patients with syncope among those affected by hypertrophic cardiomyopathy (HCM) and the relevance of syncope as risk factor for sudden cardiac death and life-threatening arrhythmic events.

Method And Results: Systematic review of original articles that assessed syncope in HCM patients. Literature search of PubMed including all English publications from 1973 to 2021.We found 57 articles for a total of 21.791 patients; of these, 14 studies reported on arrhythmic events in the follow-up. Syncope was reported in 15.8% (3.452 of 21.791) patients. It was considered unexplained in 91% of cases. Life-threatening arrhythmic events occurred in 3.6% of non-syncopal patients and in 7.7% of syncopal patients during a mean follow-up of 5.6 years. A relative risk of 1.99 (95%CI 1.39 to 2.86) was estimated for syncope patients by the random effect model using Haldane continuity correction for 0 events.

Conclusions: In the current practice, the cause of syncope remained unexplained in most patients affected by HCM. The management of patients seems mainly driven by risk stratification rather than identification of the aetiology of syncope. There is a need of precise instructions how to apply the recommendations of current guidelines to this disease, which tests are indicated and how to interpret their findings. The protocol was registered in Prospero (ID: 275963).
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http://dx.doi.org/10.1016/j.ijcard.2022.03.028DOI Listing
June 2022

Gender Related Differences in the Clinical Presentation of Hypertrophic Cardiomyopathy-An Analysis from the SILICOFCM Database.

Medicina (Kaunas) 2022 Feb 18;58(2). Epub 2022 Feb 18.

Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.

: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease that affects approximately 1 in 500 people. Due to an incomplete disease penetrance associated with numerous factors, HCM is not manifested in all carriers of genetic mutation. Although about two-thirds of patients are male, it seems that female gender is associated with more severe disease phenotype and worse prognosis. The objective of this study was to evaluate the gender related differences in HCM presentation. : This study was conducted as a part of the international multidisciplinary SILICOFCM project. Clinical information, laboratory analyses, electrocardiography, echocardiography, and genetic testing data were collected for 362 HCM patients from four clinical centers (Florence, Newcastle, Novi Sad, and Regensburg). There were 33% female patients, and 67% male patients. : Female patients were older than males (64.5 vs. 53.5 years, < 0.0005). The male predominance was present across all age groups until the age of 70, when gender distribution became comparable. Females had higher number of symptomatic individuals then males (69% vs. 52%, = 0.003), most frequently complaining of dyspnea (50% vs. 30%), followed by chest pain (30% vs. 17%), fatigue (26% vs. 13%), palpitations (22% vs. 13%), and syncope (13% vs. 8%). The most common rhythm disorder was atrial fibrillation which was present in a similar number of females and males (19% vs. 13%, = 0.218). Levels of N-terminal pro-brain natriuretic peptide were comparable between the genders (571 vs. 794 ng/L, = 0.244). Echocardiography showed similar thickness of interventricular septum (18 vs. 16 mm, = 0.121) and posterolateral wall (13 vs. 12 mm, = 0.656), however, females had a lower number of systolic anterior motion (8% vs. 16%, = 0.020) and other mitral valve abnormalities. : Female patients are underrepresented but seem to have a more pronounced clinical presentation of HCM. Therefore, establishing gender specific diagnostic criteria for HCM should be considered.
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http://dx.doi.org/10.3390/medicina58020314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879033PMC
February 2022

Association of Premature Ventricular Contraction Burden on Serial Holter Monitoring With Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

JAMA Cardiol 2022 04;7(4):378-385

Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: A high burden of premature ventricular contractions (PVCs) at disease diagnosis has been associated with an overall higher risk of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Data regarding dynamic modification of PVC burden at follow-up with Holter monitoring and its impact on arrhythmic risk in ARVC are scarce.

Objective: To describe changes in the PVC burden and to assess whether serial Holter monitoring is dynamically associated with sustained ventricular arrhythmias during follow-up in patients with ARVC.

Design, Settings, And Participants: In this cohort study, patients with a definite ARVC diagnosis, available Holter monitoring results at disease diagnosis, and at least 2 additional results of Holter monitoring during follow-up were enrolled from 6 ARVC registries in North America and Europe. Data were collected from June 1 to September 15, 2021.

Main Outcomes And Measures: The association between prespecified variables retrieved at each Holter monitoring follow-up (ie, overall PVC burden; presence of sudden PVC spikes, defined as absolute increase in PVC burden ≥5000 per 24 hours or a relative ≥75% increase, with an absolute increase of ≥1000 PVCs; presence of nonsustained ventricular tachycardia [NSVT]; and use of β-blockers and class III antiarrhythmic drugs) and sustained ventricular arrhythmias occurring within 12 months after that Holter examination was assessed using a mixed logistical model.

Results: In 169 enrolled patients with ARVC (mean [SD] age, 36.3 [15.0] years; 95 men [56.2%]), a total of 723 Holter examinations (median, 4 [IQR, 4-5] per patient) were performed during a median follow-up of 54 (IQR, 42-63) months and detected 75 PVC spikes and 67 sustained ventricular arrhythmias. The PVC burden decreased significantly from the first to the second Holter examination (mean, 2906 [95% CI, 1581-4231] PVCs per 24 hours; P < .001). A model including 24-hour PVC burden (odds ratio [OR] 1.50 [95% CI, 1.10-2.03]; P = .01), PVC spikes (OR, 6.20 [95 CI, 2.74-13.99]; P < .001), and NSVT (OR, 2.29 [95% CI, 1.10-4.51]; P = .03) at each follow-up Holter examination was associated with sustained ventricular arrhythmia occurrence in the following 12 months.

Conclusions And Relevance: These findings suggest that in patients with ARVC, changes in parameters derived from each Holter examination performed during follow-up are associated with the risk of sustained ventricular arrhythmias within 12 months of disease diagnosis.
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http://dx.doi.org/10.1001/jamacardio.2021.6016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8867390PMC
April 2022

Correction to: Evaluation of stress myocardial blood flow patterns in patients with apical hypertrophic cardiomyopathy.

J Nucl Cardiol 2022 Apr;29(2):893

Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.

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http://dx.doi.org/10.1007/s12350-022-02926-5DOI Listing
April 2022

Prevalence and predictors of bradyarrhythmias requiring permanent pacing in patients with Anderson-Fabry disease.

J Cardiovasc Electrophysiol 2022 05 15;33(5):1072-1078. Epub 2022 Feb 15.

Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.

Introduction: Bradyarrhythmias are an established red flag for storage cardiac conditions including Anderson-Fabry disease (AFD). The prevalence of bradyarrhythmias requiring a pacemaker (PM) and their timing in AFD is unresolved.

Methods: We evaluated the prevalence and predictors of PM requirement in a large AFD cohort, investigating the occurrence of bradyarrhythmias as initial versus late manifestation. We retrospectively evaluated 82 consecutive AFD patients referred to our multidisciplinary referral center from 1994 to 2020 with a median follow-up of 6.9 years, identifying those requiring pacing. Univariable analysis was performed to identify cardiac features associated with PM implantation.

Results: Five of 82 (6%) AFD patients required PM implantation (5/39, i.e., 13% of those with cardiac involvement), always in the context of advanced cardiomyopathy. In none, bradyarrhythmias were the presenting feature. Indications included sick sinus syndrome in three patients, advanced atrioventricular block in two patients. QRS prolongation during follow-up strongly correlated with the onset of bradyarrhythmias.

Conclusion: Severe bradyarrhythmias are relatively frequent in patients with AFD cardiomyopathy, but do not represent a mode of presentation, occurring late in the disease course and always in the context of advanced cardiac involvement. Monitoring QRS variations over time may help to identify patients requiring pacing.
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http://dx.doi.org/10.1111/jce.15409DOI Listing
May 2022

Evaluation of stress myocardial blood flow patterns in patients with apical hypertrophic cardiomyopathy.

J Nucl Cardiol 2022 Aug 2;29(4):1946-1951. Epub 2022 Feb 2.

Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.

Background: Among the other variants, the apical pattern of hypertrophic cardiomyopathy (AHCM) is probably the most important, with possible aneurysmatic evolution.

Methods And Results: We analyzed 12 patients with AHCM who underwent [N]NH-PET/CT. Regional perfusion, stress global myocardial blood flow (MBF), and transmural perfusion patterns were assessed. To evaluate the LV-MBF distribution, we compared the apex with septum and infero-lateral wall. Furthermore, global stress MBF distribution in AHCM patients was compared with a reference septal HCM cohort. Visual regional perfusion analysis demonstrated an apical hypoperfusion in 10 of 12 patients, without correlation with the stress MBF of the whole LV. Significant differences among stress MBF in apical, in septal, and in the infero-lateral walls were recorded (P < .02). The transmural analysis showed a significant difference among the three segment groups for epicardial (P < .003) as well for endocardial MBF (P < .005). In the post hoc analysis, the apical MBF was significantly lower than in septal and infero-lateral walls in epicardium (P < .005) and significantly lower than the infero-lateral MBF in endocardium (P < .001).

Conclusion: In patients with AHCM, more severe apical microvascular impairment was found as compared to patients with classical septal HCM, supporting the suspicion that ischemia could play a role in the future aneurysmatic evolution of AHCM.
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http://dx.doi.org/10.1007/s12350-022-02911-yDOI Listing
August 2022

Disease Progression of Hypertrophic Cardiomyopathy: Modeling Using Machine Learning.

JMIR Med Inform 2022 Feb 2;10(2):e30483. Epub 2022 Feb 2.

Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia.

Background: Cardiovascular disorders in general are responsible for 30% of deaths worldwide. Among them, hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that is present in about 1 of 500 young adults and can cause sudden cardiac death (SCD).

Objective: Although the current state-of-the-art methods model the risk of SCD for patients, to the best of our knowledge, no methods are available for modeling the patient's clinical status up to 10 years ahead. In this paper, we propose a novel machine learning (ML)-based tool for predicting disease progression for patients diagnosed with HCM in terms of adverse remodeling of the heart during a 10-year period.

Methods: The method consisted of 6 predictive regression models that independently predict future values of 6 clinical characteristics: left atrial size, left atrial volume, left ventricular ejection fraction, New York Heart Association functional classification, left ventricular internal diastolic diameter, and left ventricular internal systolic diameter. We supplemented each prediction with the explanation that is generated using the Shapley additive explanation method.

Results: The final experiments showed that predictive error is lower on 5 of the 6 constructed models in comparison to experts (on average, by 0.34) or a consortium of experts (on average, by 0.22). The experiments revealed that semisupervised learning and the artificial data from virtual patients help improve predictive accuracies. The best-performing random forest model improved R from 0.3 to 0.6.

Conclusions: By engaging medical experts to provide interpretation and validation of the results, we determined the models' favorable performance compared to the performance of experts for 5 of 6 targets.
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http://dx.doi.org/10.2196/30483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851344PMC
February 2022

Sudden cardiac death in cardiomyopathies: acting upon "acceptable" risk in the personalized medicine era.

Heart Fail Rev 2022 Jan 27. Epub 2022 Jan 27.

Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.

Patients with cardiomyopathies are confronted with the risk of sudden cardiac death (SCD) throughout their lifetime. Despite the fact that SCD is relatively rare, prognostic stratification is an integral part of physician-patient discussion, with the goal of risk modification and prevention. The current approach is based on a concept of "acceptable risk." However, there are intrinsic problems with an algorithm-based approach to risk management, magnified by the absence of robust evidence underlying clinical decision support tools, which can make high- versus low-risk classifications arbitrary. Strategies aimed at risk reduction range from selecting patients for an implantable cardioverter defibrillator (ICD) to disqualification from competitive sports. These clinical options, especially when implying the use of finite financial resources, are often delivered from the physician's perspective citing decision-making algorithms. When the burden of intervention-related risks or financial costs is deemed higher than an "acceptable risk" of SCD, the patient's perspective may not be appropriately considered. Designating a numeric threshold of "acceptable risk" has ethical implications. One could reasonably ask "acceptable to whom?" In an era when individual choice and autonomy are pillars of the physician-patient relationship, the subjective aspects of perceived risk should be acknowledged and be part of shared decision-making. This is particularly true when the lack of a strong scientific evidence base makes a dichotomous algorithm-driven approach suboptimal for unmitigated translation to clinical practice.
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http://dx.doi.org/10.1007/s10741-021-10198-3DOI Listing
January 2022

The Inglorious Art.

Authors:
Iacopo Olivotto

JAMA Cardiol 2022 02;7(2):127

Cardiomyopathy Unit, Careggi University Hospital, University of Florence, Florence, Italy.

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http://dx.doi.org/10.1001/jamacardio.2021.5701DOI Listing
February 2022

Strength of clinical indication and therapeutic impact of the implantable cardioverter defibrillator in patients with hypertrophic cardiomyopathy.

Int J Cardiol 2022 Apr 12;353:62-67. Epub 2022 Jan 12.

Cardiomyopathy Unit, Cardiothoracic and Vascular Department and Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Background: The implantable cardioverter defibrillator(ICD) has revolutionized the management of patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death (SCD). However, the identification of ideal candidates remains challenging. We aimed to describe the long-term impact of the ICD for primary prevention in patients with HCM based on stringent (high SCD risk) vs lenient indications (need for pacing/personal choice).

Methods: Data from two Italian HCM Cardiomyopathy Units were retrospectively analyzed. Only patients >1 follow-up visits were divided into two groups according to ICD candidacy:stringent (high SCD risk) and lenient (need for pacing, patients' choice, physician advice despite lack of high SCD risk). Major cardiac events (composite of appropriate shock/intervention and SCD) was the primary endpoint. A safety endpoint was defined as a composite of inappropriate shocks and device-related complications.

Results: Of 2009 patients, 252(12.5%) received an ICD, including 27(1.3%) in secondary prevention and 225(11.2%) in primary prevention (age at implantation 49 ± 16 years; men 65.3%). Among those in primary prevention, 167(74.2%) had stringent, while 58(25.8%) had lenient indications. At 5 ± 4 years, only stringent ICD patients experienced major cardiac events (2.84%/year, 5-year cumulative incidence: 8.1%, 95%CI [3.5-14.1%]). ICD-related complications were similar across stringent and lenient subgroups. However, patients implanted >60 years had a significantly higher risk of adverse events.

Conclusion: One third of ICD recipients with HCM in primary prevention received a lenient implantation and had no appropriate intervention. ICD implantation due to systematic upgrade in patients requiring pacing and increased risk perception may offer little advantage and increase complication rates.
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http://dx.doi.org/10.1016/j.ijcard.2022.01.022DOI Listing
April 2022

Sex-related differences in clinical presentation and all-cause mortality in patients with cardiac transthyretin amyloidosis and light chain amyloidosis.

Int J Cardiol 2022 Mar 4;351:71-77. Epub 2022 Jan 4.

Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy; Division of Interventional Structural Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy.

We aimed to ascertain whether sex-related differences are relevant to clinical presentation, cardiac phenotype and all-cause mortality in different types of cardiac amyloidosis, a field still poorly investigated. Medical files from consecutive patients diagnosed with cardiac amyloidosis between 2000 and 2020, at Careggi University Hospital, were retrospectively evaluated. Over this period, 259 patients (12% females) were diagnosed with wild type transthyretin amyloidosis (wtATTR), 52 (25% females) with hereditary transthyretin amyloidosis (hATTR) and 143 (47% females) with light chain amyloidosis (AL). Women with wtATTR, compared to men, were significantly older at the time of diagnosis and showed higher National Amyloidosis Centre score, thicker normalized interventricular septum, higher diastolic dysfunction and worse right ventricular function. Females with hATTR and AL had lower normalized cardiac mass compared to men, otherwise, bio-humoral parameters, NYHA class, and ECG characteristics were similar. Comparing females and male with wtATTR, hATTR and AL, no differences in Kaplan-Meier curves for all-cause mortality were observed with regard to sex, p-value >0.05. In conclusion, we did not observe major differences in clinical expression related to sex in different types of cardiac amyloidosis: specifically, all-cause mortality was not affected. Nevertheless, women with wtATTR had echocardiographic signs of more advanced disease and higher NAC score at diagnosis suggesting a possible later recognition of disease compared to men.
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http://dx.doi.org/10.1016/j.ijcard.2021.12.048DOI Listing
March 2022
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