Publications by authors named "Iacopo Olivotto"

256 Publications

Is heart failure with preserved ejection fraction a 'dementia' of the heart?

Heart Fail Rev 2021 Apr 27. Epub 2021 Apr 27.

Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.

Heart failure with preserved ejection fraction (HFpEF) remains an elusive entity, due to its heterogeneous clinical profile and an arbitrarily defined nosology. Several pathophysiological mechanisms recognized as central for the development of HFpEF appear to be in common with the process of physiological aging of the heart. Both conditions are characterized by progressive impairment in cardiac function, accompanied by left ventricular hypertrophy, diastolic dysfunction, sarcomeric, and metabolic abnormalities. The neurological paradigm of dementia-intended as a progressive, multifactorial organ damage with decline of functional reserve, eventually leading to irreversible dysfunction-is well suited to represent HFpEF. In such perspective, certain phenotypes of HFpEF may be viewed as a maladaptive response to environmental modifiers, causing premature and pathological aging of the heart. We here propose that the 'HFpEF syndrome' may reflect the interplay of adverse structural remodelling and erosion of functional reserve, mirroring the processes leading to dementia in the brain. The resulting conceptual framework may help advance our understanding of HFpEF and unravel potential therapeutical targets.
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http://dx.doi.org/10.1007/s10741-021-10114-9DOI Listing
April 2021

Changes in the perceived epidemiology of amyloidosis: 20 year-experience from a Tertiary Referral Centre in Tuscany.

Int J Cardiol 2021 Apr 15. Epub 2021 Apr 15.

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

Background: Amyloidosis is considered a rare heterogeneous condition comprising different entities. Epidemiological data are limited and often controversial. We aimed to examine epidemiological changes in amyloidosis diagnosed over a 20-year period at a tertiary referral centre for amyloidosis.

Methods: We retrospectively reviewed medical files from all patients diagnosed with amyloidosis between January 2000 and December 2019, at Careggi University Hospital, Florence, Italy. Diagnosis of amyloidosis was performed as per current clinical practice and scientific evidence at the time of patient evaluation.

Results: We reported data on 654 consecutive patients: 274 (42%) wild type transthyretin amyloidosis (wtATTR), 68 (10%) genetic variant amyloidosis (vATTR), 281 (43%) light-chain amyloidosis (AL) and 31 (5%) serum amyloid A amyloidosis (AA). With limited fluctuations, the absolute number of new AL diagnosis increased during the 20-year period. wtATTR was unrecognized before 2009 but represented by far the most common aetiology at the end of the observation period. AA represented a residual diagnosis throughout the entire examined period.

Conclusions: Following a rapid and marked increase in the number of new diagnoses over the last decade, ATTR represents by far the most common type of amyloidosis in our regional centre. These data contrasts with recent reports from national referral institutions and may help shed light on the epidemiology of the disease at the community level.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.023DOI Listing
April 2021

Endocarditis with spondylodiscitis: clinical characteristics and prognosis.

BMC Cardiovasc Disord 2021 Apr 15;21(1):186. Epub 2021 Apr 15.

Division of General Cardiology, University of Florence, Florence, Italy.

Background: The association of infective endocarditis (IE) with spondylodiscitis (SD) was first reported in 1965, but few data are available about this issue. This study aimed to evaluate the prevalence of SD in patients with IE, and to determine the clinical features and the prognostic impact of this association.

Methods: We retrospectively analysed 363 consecutive patients admitted to our Department with non-device-related IE. Radiologically confirmed SD was revealed in 29 patients (8%). Long-term follow-up (average: 3 years) was obtained by structured telephone interviews; in 95 cases (13 of whom had been affected by SD), follow-up echocardiographic evaluation was also available.

Results: At univariable analysis, the combination of IE with SD was associated with male gender (p = 0.017), diabetes (p = 0.028), drug abuse (p = 0.009), Streptococcus Viridans (p = 0.009) and Enterococcus (p = 0.015) infections. At multivariable analysis, all these factors independently correlated with presence of SD in patients with IE. Mortality was similar in patients with and without SD. IE relapses at 3 years were associated with the presence of SD (p = 0.003), Staphylococcus aureus infection (p < 0.001), and drug abuse (p < 0.001) but, at multivariable analysis, only drug abuse was an independent predictor of IE relapses (p < 0.001; HR 6.8, 95% CI 1.6-29). At echocardiographic follow-up, SD was not associated with worsening left ventricular systolic function or valvular dysfunction.

Conclusions: The association of IE with SD is not rare. Hence, patients with IE should be screened for metastatic infection of the vertebral column, especially if they have risk factors for it. However, SD does not appear to worsen the prognosis of patients with IE, either in-hospital or long-term.
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http://dx.doi.org/10.1186/s12872-021-01991-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051097PMC
April 2021

Prognostic Value of Reduced Heart Rate Reserve during Exercise in Hypertrophic Cardiomyopathy.

J Clin Med 2021 Mar 24;10(7). Epub 2021 Mar 24.

Institute of Management, Scuola Superiore Sant'Anna, 56127 Pisa, Italy.

Background: Sympathetic dysfunction can be evaluated by heart rate reserve (HRR) with exercise test.

Objectives: To determine the value of HRR in predicting outcome of patients with hypertrophic cardiomyopathy (HCM).

Methods: We enrolled 917 HCM patients (age = 49 ± 15 years, 516 men) assessed with exercise stress echocardiography (ESE) in 11 centres. ESE modality was semi-supine bicycle in 51 patients (6%), upright bicycle in 476 (52%), and treadmill in 390 (42%). During ESE, we assessed left ventricular outflow tract obstruction (LVOTO), stress-induced new regional wall motion abnormalities (RWMA), and HRR (peak/rest heart rate, HR). By selection, all patients completed the follow-up. Mortality was the predetermined outcome measure Results: During ESE, RWMA occurred in 22 patients (2.4%) and LVOTO (≥50 mmHg) in 281 (30.4%). HRR was 1.90 ± 0.40 (lowest quartile ≤ 1.61, highest quartile > 2.13). Higher resting heart rate (odds ratio 1.027, 95% CI: 1.018-1.036, < 0.001), older age (odds ratio 1.021, 95% CI: 1.009-1.033, < 0.001), lower exercise tolerance (mets, odds ratio 0.761, 95% CI: 0.708-0.817, 0.001) and resting LVOTO (odds ratio 1.504, 95% CI: 1.043-2.170, 0.029) predicted a reduced HRR. During a median follow-up of 89 months (interquartile range: 36-145 months), 90 all-cause deaths occurred. At multivariable analysis, lowest quartile HRR (Hazard ratio 2.354, 95% CI 1.116-4.968 = 0.025) and RWMA (Hazard ratio 3.279, 95% CI 1.441-7.461 0.004) independently predicted death, in addition to age (Hazard ratio 1.064, 95% CI 1.043-1.085 0.001) and maximal wall thickness (Hazard ratio 1.081, 95% CI 1.037-1.128, < 0.001).

Conclusions: A blunted HRR during ESE predicts survival independently of RWMA in HCM patients.
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http://dx.doi.org/10.3390/jcm10071347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037369PMC
March 2021

Emerging Medical Treatment for Hypertrophic Cardiomyopathy.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Cardiomyopathy Unit, Careggi University Hospital, 50134 Florence, Italy.

Hypertrophic cardiomyopathy (HCM) is a common myocardial disease characterized by otherwise unexplained left ventricular hypertrophy. The main cause of disabling symptoms in patients with HCM is left ventricular outflow tract (LVOT) obstruction. This phenomenon is multifactorial, determined both by anatomical and functional abnormalities: myocardial hypercontractility is believed to represent one of its major determinants. The anatomical anomalies are targeted by surgical interventions, whereas attenuating hypercontractility is the objective of old and new drugs including the novel class of allosteric myosin inhibitors. This review summarizes the current treatment modalities and discusses the emerging therapeutical opportunities focusing on the recently developed cardiac myosin ATPase inhibitors Mavacamten and CK-274. Novel surgical and interventional approaches are also discussed.
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http://dx.doi.org/10.3390/jcm10050951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957690PMC
March 2021

Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation.

Genet Med 2021 Mar 29. Epub 2021 Mar 29.

Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Purpose: Variants in MYBPC3 causing loss of function are the most common cause of hypertrophic cardiomyopathy (HCM). However, a substantial number of patients carry missense variants of uncertain significance (VUS) in MYBPC3. We hypothesize that a structural-based algorithm, STRUM, which estimates the effect of missense variants on protein folding, will identify a subgroup of HCM patients with a MYBPC3 VUS associated with increased clinical risk.

Methods: Among 7,963 patients in the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe), 120 unique missense VUS in MYBPC3 were identified. Variants were evaluated for their effect on subdomain folding and a stratified time-to-event analysis for an overall composite endpoint (first occurrence of ventricular arrhythmia, heart failure, all-cause mortality, atrial fibrillation, and stroke) was performed for patients with HCM and a MYBPC3 missense VUS.

Results: We demonstrated that patients carrying a MYBPC3 VUS predicted to cause subdomain misfolding (STRUM+, ΔΔG ≤ -1.2 kcal/mol) exhibited a higher rate of adverse events compared with those with a STRUM- VUS (hazard ratio = 2.29, P = 0.0282). In silico saturation mutagenesis of MYBPC3 identified 4,943/23,427 (21%) missense variants that were predicted to cause subdomain misfolding.

Conclusion: STRUM identifies patients with HCM and a MYBPC3 VUS who may be at higher clinical risk and provides supportive evidence for pathogenicity.
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http://dx.doi.org/10.1038/s41436-021-01134-9DOI Listing
March 2021

The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy.

Eur J Prev Cardiol 2021 Mar 27. Epub 2021 Mar 27.

Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Aims: The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events.

Methods And Results: Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0-7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93-2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484-0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7.

Conclusion: In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.
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http://dx.doi.org/10.1093/eurjpc/zwab046DOI Listing
March 2021

Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy.

Eur Heart J 2021 Mar 26. Epub 2021 Mar 26.

Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.

Aims: Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM.

Methods And Results: We performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [<1 year (infancy), 1-18 years (childhood), >18 years (adulthood)] and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 184 (2.4%) patients were diagnosed in infancy; 1128 (14.7%) in childhood; and 6365 (82.9%) in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following baseline visit, but HF and AF becoming more common by the end of the 2nd decade. Sarcomeric variants were more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a greater than two-fold increased risk of HF [HRadj 2.39 (1.36-4.20), P = 0.003] and 67% increased risk of the overall composite outcome [HRadj 1.67 (1.16-2.41), P = 0.006]. When compared with adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias [HRadj 1.36 (1.03-1.80)] and twice as likely to require transplant or ventricular assist device [HRadj 1.99 (1.23-3.23)].

Conclusion: Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into the natural history of disease and can help inform clinical risk stratification.
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http://dx.doi.org/10.1093/eurheartj/ehab148DOI Listing
March 2021

Combined Effect of Mediterranean Diet and Aerobic Exercise on Weight Loss and Clinical Status in Obese Symptomatic Patients with Hypertrophic Cardiomyopathy.

Heart Fail Clin 2021 Apr 10;17(2):303-313. Epub 2021 Feb 10.

Cardiomyopathy Unit and Genetic Unit, Careggi University Hospital, Largo Brambrilla, 50134 Florence, Italy.

We evaluated the impact of weight loss (WL) using a Mediterranean diet and mild-to-moderate-intensity aerobic exercise program, on clinical status of obese, symptomatic patients with hypertrophic cardiomyopathy (HCM). Compared with nonresponders, responders showed a significant reduction of left atrial diameter, left atrial volume index (LAVI), E/E'average, pulmonary artery systolic pressure (PASP), and a significant increase in Vo (%) and peak workload. Body mass index changes correlated with reduction in left atrial diameter, LAVI, E/E'average, PASP, and increase of Vo (mL/Kg/min), Vo (%), peak workload. Mediterranean diet and aerobic exercise is associated with clinical-hemodynamic improvement in obese symptomatic HCM patients.
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http://dx.doi.org/10.1016/j.hfc.2021.01.003DOI Listing
April 2021

Epidemiology of cardiomyopathies: essential context knowledge for a tailored clinical work-up.

Eur J Prev Cardiol 2020 Nov 7. Epub 2020 Nov 7.

Department of Clinical Cardiology, Policlinico di Monza, Via Carlo Amati, 111, 20900 Monza, Italy.

Cardiomyopathies (CMPs) are primary disorders of myocardial structure and function in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease. Knowledge of the incidence and prevalence of CMPs may help clinicians to compare their observations in clinical practice with expected cases per person-year and to avoid under-reporting in clinical context. Currently, available estimates of prevalence and incidence of CMPs are based on clinical data, collected with a wide variability in population-source, and before the genetic testing evolved as a standard diagnostic tool. This review focuses on the epidemiology of CMPs in subjects aged between 18 and 55 years. A structured up-to-date diagnostic flow-chart for CMPs diagnosis and assessment is proposed to avoid misdiagnosis of CMPs in the young population and in subjects with unexplained cardiac disorders.
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http://dx.doi.org/10.1093/eurjpc/zwaa035DOI Listing
November 2020

Prescribing, dosing and titrating exercise in patients with hypertrophic cardiomyopathy for prevention of comorbidities: Ready for prime time.

Eur J Prev Cardiol 2020 Jun 17. Epub 2020 Jun 17.

Department of Medical Biotechnologies, Division of Cardiology, University of Siena, Italy.

The benefits of physical activity are well established, leading to both cardiovascular and non-cardiovascular benefits, improving quality of life and reducing mortality. Despite such striking body of evidence, patients with hypertrophic cardiomyopathy are often discouraged by health professionals to practice physical activity and personalised exercise prescription is an exception rather than the rule. As a result, hypertrophic cardiomyopathy patients are on average less active and spend significantly less time at work or recreational physical activity than the general population. Exercise restriction derives from the evidence that vigorous exercise may occasionally trigger life-threatening arrhythmias and sudden cardiac death. However, while participation in competitive sports should be prudentially denied, hypertrophic cardiomyopathy patients can benefit from the positive effects of regular physical activity, aimed to reduce the risk of comorbidities and improve the quality of life. Based on this rationale, exercise should be prescribed and titrated just like a drug in hypertrophic cardiomyopathy patients, considering individual characteristics, symptoms, past medical history, objective individual response to exercise, previous training experience and stage of disease. Type, frequency, duration, and intensity should be defined on a personal basis. Yet exercise prescription in hypertrophic cardiomyopathy and its long-term effects represent major gaps in our current knowledge and require extensive research. We here review existing evidence regarding benefits and hazards of physical activity, with specific focus on viable modalities for tailored and safe exercise prescription in these patients, highlighting future developments and relevant research targets.
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http://dx.doi.org/10.1177/2047487320928654DOI Listing
June 2020

Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week.

J Am Coll Cardiol 2021 Feb;77(7):922-936

Hôpitaux Universitaires de Genève, Genève, Switzerland.

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving.
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http://dx.doi.org/10.1016/j.jacc.2020.12.024DOI Listing
February 2021

The coronary microcirculation in sepsis: not of micro-importance.

Glob Cardiol Sci Pract 2020 Dec 31;2020(3):e202030. Epub 2020 Dec 31.

Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.

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http://dx.doi.org/10.21542/gcsp.2020.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868102PMC
December 2020

Standard ECG for differential diagnosis between Anderson-Fabry disease and hypertrophic cardiomyopathy.

Heart 2021 Feb 9. Epub 2021 Feb 9.

Cardiology Unit, IRCCS, Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola Hospital, University of Bologna, Bologna, Emilia-Romagna, Italy

Objectives: To evaluate the role of the ECG in the differential diagnosis between Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM).

Methods: In this multicentre retrospective study, 111 AFD patients with left ventricular hypertrophy were compared with 111 patients with HCM, matched for sex, age and maximal wall thickness by propensity score. Independent ECG predictors of AFD were identified by multivariate analysis, and a multiparametric ECG score-based algorithm for differential diagnosis was developed.

Results: Short PR interval, prolonged QRS duration, right bundle branch block (RBBB), R in augmented vector left (aVL) ≥1.1 mV and inferior ST depression independently predicted AFD diagnosis. A point-by-point ECG score was then derived with the following diagnostic performances: c-statistic 0.80 (95% CI 0.74 to 0.86) for discrimination, the Hosmel-Lemeshow χ 6.14 (p=0.189) for calibration, sensitivity 69%, specificity 84%, positive predictive value 82% and negative predictive value 72%. After bootstrap resampling, the mean optimism was 0.025, and the internal validated c-statistic for the score was 0.78.

Conclusions: Standard ECG can help to differentiate AFD from HCM while investigating unexplained left ventricular hypertrophy. Short PR interval, prolonged QRS duration, RBBB, R in aVL ≥1.1 mV and inferior ST depression independently predicted AFD. Their systematic evaluation and the integration in a multiparametric ECG score can support AFD diagnosis.
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http://dx.doi.org/10.1136/heartjnl-2020-318271DOI Listing
February 2021

Mavacamten for hypertrophic obstructive cardiomyopathy - Authors' reply.

Lancet 2021 Jan;397(10272):369-370

Cardiomyopathy Unit, Azienda Ospedaliera Universitaria Careggi, Florence 50134, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(20)32391-6DOI Listing
January 2021

Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies.

Genet Med 2021 May 26;23(5):856-864. Epub 2021 Jan 26.

Amsterdam UMC, University of Amsterdam, Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam, Netherlands.

Purpose: To characterize the genetic architecture of left ventricular noncompaction (LVNC) and investigate the extent to which it may represent a distinct pathology or a secondary phenotype associated with other cardiac diseases.

Methods: We performed rare variant association analysis with 840 LVNC cases and 125,748 gnomAD population controls, and compared results to similar analyses on dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM).

Results: We observed substantial genetic overlap indicating that LVNC often represents a phenotypic variation of DCM or HCM. In contrast, truncating variants in MYH7, ACTN2, and PRDM16 were uniquely associated with LVNC and may reflect a distinct LVNC etiology. In particular, MYH7 truncating variants (MYH7tv), generally considered nonpathogenic for cardiomyopathies, were 20-fold enriched in LVNC cases over controls. MYH7tv heterozygotes identified in the UK Biobank and healthy volunteer cohorts also displayed significantly greater noncompaction compared with matched controls. RYR2 exon deletions and HCN4 transmembrane variants were also enriched in LVNC, supporting prior reports of association with arrhythmogenic LVNC phenotypes.

Conclusion: LVNC is characterized by substantial genetic overlap with DCM/HCM but is also associated with distinct noncompaction and arrhythmia etiologies. These results will enable enhanced application of LVNC genetic testing and help to distinguish pathological from physiological noncompaction.
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http://dx.doi.org/10.1038/s41436-020-01049-xDOI Listing
May 2021

The Investigative Role of Statins in Ameliorating Lower Urinary Tract Symptoms (LUTS): A Systematic Review.

J Clin Med 2021 Jan 22;10(3). Epub 2021 Jan 22.

Department of Minimally Invasive and Robotic Urologic Surgery and Kidney Transplantation, University of Florence, 50100 Florence, Italy.

Previous data have shown that patients with metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE) could be refractory to the medical treatment. In this context, the evidence suggests a role for statin use in LUTS/BPE patients. The present systematic review aimed to evaluate the impact of statins on the treatment of men with LUTS/BPE. This review has been registered on PROSPERO (CRD42019120729). A systematic review of English-language literature was performed up to January 2020 in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA statement) criteria. Retrieved studies had to include adults with LUTS connected to BPE treated with statins drugs for metabolic syndrome. After removing duplicates, a total of 381 studies were identified by the literature search and independently screened. Of these articles, 10 fit the inclusion criteria and were further assessed for eligibility. Data from our systematic review suggest that a long-term therapy with statins, at least 6 months, is required to achieve significant impacts on prostate tissue and LUTS. Moreover, besides statins' direct activity, the risk reduction of LUTS might be connected to the improvement of hypercholesterolemia and MetS. The role of statins for the treatment of LUTS/BPE may be beneficial; however, evidence from robust studies is not enough, and more clinical trial are required.
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http://dx.doi.org/10.3390/jcm10030416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865704PMC
January 2021

Arrhythmogenic potential of myocardial disarray in hypertrophic cardiomyopathy: genetic basis, functional consequences and relation to sudden cardiac death.

Europace 2021 Jan 14. Epub 2021 Jan 14.

Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.

Myocardial disarray is defined as disorganized cardiomyocyte spatial distribution, with loss of physiological fibre alignment and orientation. Since the first pathological descriptions of hypertrophic cardiomyopathy (HCM), disarray appeared as a typical feature of this condition and sparked vivid debate regarding its specificity to the disease and clinical significance as a diagnostic marker and a risk factor for sudden death. Although much of the controversy surrounding its diagnostic value in HCM persists, it is increasingly recognized that myocardial disarray may be found in physiological contexts and in cardiac conditions different from HCM, raising the possibility that central focus should be placed on its quantity and distribution, rather than a mere presence. While further studies are needed to establish what amount of disarray should be considered as a hallmark of the disease, novel experimental approaches and emerging imaging techniques for the first time allow ex vivo and in vivo characterization of the myocardium to a molecular level. Such advances hold the promise of filling major gaps in our understanding of the functional consequences of myocardial disarray in HCM and specifically on arrhythmogenic propensity and as a risk factor for sudden death. Ultimately, these studies will clarify whether disarray represents a major determinant of the HCM clinical profile, and a potential therapeutic target, as opposed to an intriguing but largely innocent bystander.
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http://dx.doi.org/10.1093/europace/euaa348DOI Listing
January 2021

Predictors of mortality and adverse events in patients with infective endocarditis: a retrospective real world study in a surgical centre.

BMC Cardiovasc Disord 2021 Jan 12;21(1):28. Epub 2021 Jan 12.

Division of General Cardiology, Cardiothoracovascular Department, Azienda Ospedaliero-Universitaria Careggi and University of Florence, Florence, Italy.

Purpose: Mortality in infective endocarditis (IE) is still high, and the long term prognosis remains uncertain. This study aimed to identify predictors of long-term mortality for any cause, adverse event rate, relapse rate, valvular and ventricular dysfunction at follow-up, in a real-world surgical centre.

Methods: We retrospectively analyzed 363 consecutive episodes of IE (123 women, 34%) admitted to our department with a definite diagnosis of non-device-related IE. Median follow-up duration was 2.9 years. Primary endpoints were predictors of mortality, recurrent endocarditis, and major non-fatal adverse events (hospitalization for any cardiovascular cause, pace-maker implantation, new onset of atrial fibrillation, sternal dehiscence), and ventricular and valvular dysfunction at follow-up.

Results: Multivariate analysis independent predictors of mortality showed age (HR per unit 1.031, p < 0.003), drug abuse (HR 3.5, p < 0.002), EUROSCORE II (HR per unit 1.017, p < 0.0006) and double valve infection (HR 2.3, p < 0.001) to be independent predictors of mortality, while streptococcal infection remained associated with a better prognosis (HR 0.5, p < 0.04). Major non-fatal adverse events were associated with age (HR 1.4, p < 0.022). New episodes of infection were correlated with S aureus infection (HR 4.8, p < 0.001), right-sided endocarditis (HR 7.4, p < 0.001), spondylodiscitis (HR 6.8, p < 0.004) and intravenous drug abuse (HR 10.3, p < 0.001). After multivariate analysis, only drug abuse was an independent predictor of new episodes of endocarditis (HR 8.5, p < 0.001). Echocardiographic follow-up, available in 95 cases, showed a worsening of left ventricular systolic function (p < 0.007); severe valvular dysfunction at follow-up was reported only in 4 patients, all of them had mitral IE (p < 0.03).

Conclusions: The present study highlights some clinical, readily available factors that can be useful to stratify the prognosis of patients with IE.
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http://dx.doi.org/10.1186/s12872-021-01853-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802147PMC
January 2021

Transcatheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy: Long-term results and clinical outcomes.

J Cardiovasc Electrophysiol 2021 Mar 24;32(3):657-666. Epub 2021 Jan 24.

Division of Cardiology, Department of Medical Sciences, "Città della Salute della Scienza" Hospital, University of Turin, Turin, Italy.

Introduction: Radiofrequency transcatheter ablation (RFCA) for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) has been proven feasible. However, the long-term results of RFCA and its impact on clinical course of HCM are unknown. The aim of this study was to analyse clinical outcomes and long-term efficacy of RFCA in a multicentre cohort of patients with HCM and concomitant AF.

Methods: Patients with HCM and AF consecutively undergoing RFCA were included. Ablation failure was defined as recurrence of AF, atrial tachycardia, or flutter lasting more than 3 min and occurring after the blanking period.

Results: Overall, 116 patients with symptomatic AF refractory to antiarrhythmic drugs were included. Over a median follow-up of 6.0 years (interquartile range: 3.0-8.9 years) recurrence rate after a single RFCA was 32.3 per 100 patient/years with 26% of patients free from AF relapses at 6-year follow-up. Among patients experiencing AF recurrence, 51 (66%) underwent at least one redo-procedure. The overall recurrence rate considering redo-procedures was 12.6 per 100 patients/years with 53% of patients free from AF relapses at 6 years. At last follow-up, with an average of 1.6 procedures, 67 (61%) patients were in sinus rhythm (SR). Patients remaining in SR showed better functional status compared with those experiencing arrhythmic recurrences (NYHA Class 1.6 ± 0.1 vs. 2.0 ± 0.1, p = .009).

Conclusions: RFCA of AF in HCM patients is an effective and safe strategy favoring long-term SR maintenance, reduction of atrial arrhythmic events, and improved functional status. However, most patients need repeat procedures and continuation of antiarrhythmic drugs.
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http://dx.doi.org/10.1111/jce.14880DOI Listing
March 2021

A rare case of pediatric cardiomyopathy: Alström syndrome identified by gene panel analysis.

Clin Case Rep 2020 Dec 27;8(12):3369-3373. Epub 2020 Oct 27.

Cardiology Unit Meyer Children's Hospital Florence Italy.

Genetic investigation of early-onset Dilatative cardiomyopathy phenotype, including molecular autopsy, is the key to appropriate recognition and management of rare etiologies and atypical presentations and to offer genetic counseling to the family.
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http://dx.doi.org/10.1002/ccr3.3327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752570PMC
December 2020

Cardiac involvement in eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome): Prospective evaluation at a tertiary referral centre.

Eur J Intern Med 2021 Mar 23;85:68-79. Epub 2020 Dec 23.

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

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population.

Methods: Between October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses.

Results: 52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /μl vs CSI-: 3000 /μl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy.

Conclusions: CSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.
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http://dx.doi.org/10.1016/j.ejim.2020.12.008DOI Listing
March 2021

Coronary microvascular function is impaired in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Eur J Neurol 2020 Dec 12. Epub 2020 Dec 12.

Stroke Unit, Emergency Department, AOU Careggi, Florence, Italy.

Background And Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited disease caused by NOTCH3 gene mutations. Although the main clinical features reflect brain injury, CADASIL is a systemic microangiopathy, and cardiac involvement has been observed but not systematically assessed. We aimed to study the prevalence and severity of coronary microvascular dysfunction (CMD) in CADASIL patients.

Methods: Seventeen patients with genetically confirmed CADASIL, aged <60 years (mean age 40 ± 9 years), with ≤1 cardiovascular risk factor underwent neurological and neuropsychological evaluation, 3T brain magnetic resonance imaging (MRI), 12-lead electrocardiography (ECG), standard echocardiography, and measurement of myocardial blood flow at rest (resting MBF) and of maximal myocardial blood flow following Regadenoson infusion (Reg-MBF) by NH positron emission tomography (PET). Coronary flow reserve (CFR) was defined as Reg-MBF/resting MBF. PET results were compared to those of 15 healthy controls who were age and sex matched.

Results: Twelve patients (71%) presented migraine, none (53%) had psychiatric disturbances, and one (6%) had a previous stroke. None had cognitive impairment or ECG or echocardiography abnormalities. Both Reg-MBF and CFR were blunted in CADASIL patients compared with controls (Reg-MBF 2.46 ± 0.54 vs. 3.09 ± 0.44 ml/g/min, respectively; p < 0.01; CFR 2.74 ± 0.36 vs. 3.28 ± 0.66, respectively, p < 0.01). No correlations were found between Reg-MBF values and neuropsychological performance or cerebral lesion burden on MRI.

Conclusions: CADASIL patients exhibit blunted CFR due to CMD, which can be severe and is independent of the severity of brain lesion load and cognitive performances. CADASIL is a systemic microcirculation disease, and active surveillance of cardiac symptoms should be considered in these patients.
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http://dx.doi.org/10.1111/ene.14678DOI Listing
December 2020

Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy.

BMC Cardiovasc Disord 2020 12 9;20(1):516. Epub 2020 Dec 9.

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

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.

Methods: As a part of the international multidisciplinary SILICOFCM project ( www.silicofcm.eu ) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.

Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e' ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079).

Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.
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http://dx.doi.org/10.1186/s12872-020-01807-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727200PMC
December 2020

Associations Between Female Sex, Sarcomere Variants, and Clinical Outcomes in Hypertrophic Cardiomyopathy.

Circ Genom Precis Med 2021 Feb 7;14(1):e003062. Epub 2020 Dec 7.

Brigham and Women's Hospital (N.K.L., A.L.C., C.E.S., C.Y.H.), Harvard Medical School, MA.

Background: The impact of sex on phenotypic expression in hypertrophic cardiomyopathy (HCM) has not been well characterized in genotyped cohorts.

Methods: Retrospective cohort study from an international registry of patients receiving care at experienced HCM centers. Sex-based differences in baseline characteristics and clinical outcomes were assessed.

Results: Of 5873 patients (3788 genotyped), 2226 (37.9%) were women. At baseline, women were older (49.0±19.9 versus 42.9±18.4 years, <0.001) and more likely to have pathogenic/likely pathogenic sarcomeric variants (HCM patients with a sarcomere mutation; 51% versus 43%, <0.001) despite equivalent utilization of genetic testing. Age at diagnosis varied by sex and genotype despite similar distribution of causal genes. Women were 3.6 to 7.1 years older at diagnosis (<0.02) except for patients with variants where age at diagnosis was comparable for women and men (n=492; 34.8±19.2 versus 33.3±16.8 years, =0.39). Over 7.7 median years of follow-up, New York Heart Association III-IV heart failure was more common in women (hazard ratio, 1.87 [CI, 1.48-2.36], <0.001), after controlling for their higher burden of symptoms and outflow tract obstruction at baseline, reduced ejection fraction, HCM patients with a sarcomere mutation, age, and hypertension. All-cause mortality was increased in women (hazard ratio, 1.50 [CI, 1.13-1.99], <0.01) but neither implantable cardioverter-defibrillator utilization nor ventricular arrhythmia varied by sex.

Conclusions: In HCM, women are older at diagnosis, partly modified by genetic substrate. Regardless of genotype, women were at higher risk of mortality and developing severe heart failure symptoms. This points to a sex-effect on long-term myocardial performance in HCM, which should be investigated further.
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http://dx.doi.org/10.1161/CIRCGEN.120.003062DOI Listing
February 2021

[Clinical pathway for cardiomyopathies: a genetic testing strategy proposed by ANMCO in Tuscany].

G Ital Cardiol (Rome) 2020 Dec;21(12):926-934

Dipartimento di Cardiologia, Ospedale Versilia, Lucca.

Hereditary cardiomyopathies, hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, restrictive cardiomyopathy and left ventricular noncompaction, are clinically and genetically very heterogeneous diseases, and they represent a frequent cause of cardiac arrest and sudden death. To date, over 100 genes are known to be associated with the onset of cardiomyopathies. Genetic testing is performed by next generation sequencing, a technology that has made it possible to analyze hundreds of genes in many patients simultaneously, shortening costs and execution times. However, with the use of this technology, new problems have arisen regarding the indications for access to the test, the interpretation of the data and the clinical implications of the results.This document aims to represent an operational support tool for hospital cardiologists to make the use of genetic testing more accessible and appropriate for their patients with suspected or ascertained hereditary cardiomyopathy.
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http://dx.doi.org/10.1714/3472.34547DOI Listing
December 2020