RESUMEN
Anderson-Fabry disease (AFD), a genetic disorder caused by mutations in the α-galactosidase-A (GLA) gene, disrupts lysosomal function, leading to vascular complications. The accumulation of globotriaosylceramide (Gb3) in arterial walls triggers upregulation of adhesion molecules, decreases endothelial nitric oxide synthesis, and induces reactive oxygen species production. This cascade results in fibrotic thickening, endothelial dysfunction, hypercontractility, vasospasm, and a pro-thrombotic phenotype. AFD patients display increased intima-media thickness (IMT) and reduced flow-mediated dilation (FMD), indicating heightened cardiovascular risk. Nailfold capillaroscopy (NFC) shows promise in diagnosing and monitoring microcirculatory disorders in AFD, though it remains underexplored. Morphological evidence of AFD as a storage disorder can be demonstrated through electron microscopy and immunodetection of Gb3. Secondary pathophysiological disturbances at cellular, tissue, and organ levels contribute to the clinical manifestations, with prominent lysosomal inclusions observed in vascular, cardiac, renal, and neuronal cells. Chronic accumulation of Gb3 represents a state of ongoing toxicity, leading to increased cell turnover, particularly in vascular endothelial cells. AFD-related vascular pathology includes increased renin-angiotensin system activation, endothelial dysfunction, and smooth muscle cell proliferation, resulting in IMT increase. Furthermore, microvascular alterations, such as atypical capillaries observed through NFC, suggest early microvascular involvement. This review aims to unravel the complex interplay between inflammation, oxidative stress, and endothelial dysfunction in AFD, highlighting the potential connections between metabolic disturbances, oxidative stress, inflammation, and fibrosis in vascular and cardiac complications. By exploring novel cardiovascular risk factors and potential diagnostic tools, we can advance our understanding of these mechanisms, which extend beyond sphingolipid accumulation to include other significant contributors to disease pathogenesis. This comprehensive approach can pave the way for innovative therapeutic strategies and improved patient outcomes.
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Endotelio Vascular , Enfermedad de Fabry , Inflamación , Estrés Oxidativo , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/metabolismo , Enfermedad de Fabry/fisiopatología , Enfermedad de Fabry/patología , Humanos , Inflamación/patología , Inflamación/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/patología , Animales , alfa-Galactosidasa/metabolismo , Factores de Riesgo de Enfermedad CardiacaRESUMEN
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.
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Enfermedades Cardiovasculares/diagnóstico , Manejo de la Enfermedad , Diagnóstico Precoz , Imidazoles/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piridazinas/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios de Seguimiento , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Inhibidores de Proteínas Quinasas/efectos adversos , Factores de RiesgoRESUMEN
Anthracyclines are the cornerstone for many oncologic treatments, but their cardiotoxicity has been recognized for several decades. Female subjects, especially before puberty and adolescence, or after menopause, seem to be more at increased risk, with the prognostic impact of this sex issue being less consistent compared to other cardiovascular risk factors. Several studies imply that sex differences could depend on the lack of the protective effect of sex hormones against the anthracycline-initiated damage in cardiac cells, or on differential mitochondria-related oxidative gene expression. This is also reflected by the results obtained with different diagnostic methods, such as cardiovascular biomarkers and imaging techniques (echocardiography, magnetic resonance, and nuclear medicine) in the diagnosis and monitoring of cardiotoxicity, confirming that sex differences exist. The same is true about protective strategies from anthracycline cardiotoxicity. Indeed, first studied to withstand oxidative damage in response to ischemia/reperfusion (I/R) injury, cardioprotection has different outcomes in men and women. A number of studies assessed the differences in I/R response between male and female hearts, with oxidative stress and apoptosis being shared mechanisms between the I/R and anthracyclines heart damage. Sex hormones can modulate these mechanisms, thus confirming their importance in the pathophysiology in cardioprotection not only from the ischemia/reperfusion damage, but also from anthracyclines, fueling further cardio-oncologic research on the topic.
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Antraciclinas/toxicidad , Cardiotoxicidad/etiología , Insuficiencia Cardíaca/inducido químicamente , Corazón/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Antraciclinas/efectos adversos , Biomarcadores/metabolismo , Cardiotónicos/farmacología , Cardiotoxicidad/diagnóstico por imagen , Cardiotoxicidad/epidemiología , Cardiotoxicidad/metabolismo , Ecocardiografía/métodos , Femenino , Hormonas Esteroides Gonadales/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Mitocondrias/metabolismo , Medicina Nuclear/métodos , Estrés Oxidativo/efectos de los fármacos , Pronóstico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Factores de Riesgo , Caracteres SexualesRESUMEN
BACKGROUND: The effectiveness trial "Stress echo (SE) 2020" evaluates novel applications of SE in and beyond coronary artery disease. The core protocol also includes 4-site simplified scan of B-lines by lung ultrasound, useful to assess pulmonary congestion. PURPOSE: To provide web-based upstream quality control and harmonization of B-lines reading criteria. METHODS: 60 readers (all previously accredited for regional wall motion, 53 B-lines naive) from 52 centers of 16 countries of SE 2020 network read a set of 20 lung ultrasound video-clips selected by the Pisa lab serving as reference standard, after taking an obligatory web-based learning 2-h module ( http://se2020.altervista.org ). Each test clip was scored for B-lines from 0 (black lung, A-lines, no B-lines) to 10 (white lung, coalescing B-lines). The diagnostic gold standard was the concordant assessment of two experienced readers of the Pisa lab. The answer of the reader was considered correct if concordant with reference standard reading ±1 (for instance, reference standard reading of 5 B-lines; correct answer 4, 5, or 6). The a priori determined pass threshold was 18/20 (≥ 90%) with R value (intra-class correlation coefficient) between reference standard and recruiting center) > 0.90. Inter-observer agreement was assessed with intra-class correlation coefficient statistics. RESULTS: All 60 readers were successfully accredited: 26 (43%) on first, 24 (40%) on second, and 10 (17%) on third attempt. The average diagnostic accuracy of the 60 accredited readers was 95%, with R value of 0.95 compared to reference standard reading. The 53 B-lines naive scored similarly to the 7 B-lines expert on first attempt (90 versus 95%, p = NS). Compared to the step-1 of quality control for regional wall motion abnormalities, the mean reading time per attempt was shorter (17 ± 3 vs 29 ± 12 min, p < .01), the first attempt success rate was higher (43 vs 28%, p < 0.01), and the drop-out of readers smaller (0 vs 28%, p < .01). CONCLUSIONS: Web-based learning is highly effective for teaching and harmonizing B-lines reading. Echocardiographers without previous experience with B-lines learn quickly.
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Ecocardiografía de Estrés/normas , Pulmón/diagnóstico por imagen , Edema Pulmonar/diagnóstico , Control de Calidad , Femenino , Humanos , Internet , Masculino , Persona de Mediana EdadRESUMEN
Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme α-galactosidase A (α-Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the α-Gal A. To date, more than 900 mutations in this gene have been described. In our laboratories, the study of genetic and enzymatic alterations related to FD was performed in about 17,000 subjects with a symptomatology referable to this disorder. The accumulation of globotriaosylsphingosine (LysoGb3) was determined in blood of positives. Exonic mutations in the GLA gene were detected in 471 patients (207 Probands and 264 relatives): 71.6% of mutations were associated with the classic phenotype, 19.8% were associated with the late-onset phenotype, and 8.6% of genetic variants were of unknown significance (GVUS). The accumulation of LysoGb3 was found in all male patients with a mutation responsible for classic or late-onset FD. LysoGb3 levels were consistent with the type of mutations and the symptomatology of patients. α-Gal A activity in these patients is absent or dramatically reduced. In recent years, confusion about the pathogenicity of some mutations led to an association between non-causative mutations and FD. Our study shows that the identification of FD patients is possible by associating clinical history, GLA gene analysis, α-Gal A assay, and blood accumulation of LysoGB3. In our experience, LysoGB3 can be considered a reliable marker, which is very useful to confirm the diagnosis of Fabry disease.
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Enfermedad de Fabry/genética , Glucolípidos/genética , Mutación , Esfingolípidos/genética , alfa-Galactosidasa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Sustitución de Aminoácidos , Biomarcadores , Niño , Preescolar , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Fenotipo , Adulto JovenRESUMEN
Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal models of chemotherapy-induced cardiomyopathy. This Position Paper of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to: (1) define the distinctive etiopatogenetic features of cardiac toxicity induced by cancer therapy in humans, which include new aspects of mitochondrial function and oxidative stress, neuregulin-1 modulation through the ErbB receptor family, angiogenesis inhibition, and cardiac stem cell depletion and/or dysfunction; (2) review the new, more promising therapeutic strategies for cardioprotection, aimed to increase the survival of patients with severe antineoplastic-induced cardiotoxicity; (3) recommend the distinctive pathological features of cardiotoxicity induced by cancer therapy in humans that should be present in animal models used to identify or to test new cardioprotective therapies.
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Antineoplásicos/efectos adversos , Cardiotónicos/farmacología , Cardiotoxicidad , Neoplasias/tratamiento farmacológico , Animales , Cardiotoxicidad/etiología , Cardiotoxicidad/metabolismo , Cardiotoxicidad/prevención & control , Modelos Animales de Enfermedad , Humanos , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/fisiología , Neurregulina-1/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
The hemodynamic load due to physical activity leads to structural and functional cardiac adaptations known as "Athlete's heart". We aimed to compare myocardial performance in different groups of trained athletes by means of 3D echocardiography and 3D speckle tracking echocardiography (3D-STE). 66 athletes [26 strength-trained athletes (STA) and 40 endurance athletes (ETA)] were prospectively enrolled. A control group of 40 sedentary subjects (sedentary group) was also included. All subjects underwent both standard and 3D evaluation of left ventricular (LV) function including 3D-STE. Left ventricular mass indexed for body surface area, LV end-diastolic (LV Dd) thickness of interventricular septum and posterior wall thickness mean values were significantly increased in athletes (p < 0.001, p < 0.01 and p < 0.001, respectively). LV diastolic diameter index had a significantly higher mean value in ETA in respect to sedentary group (p = 0.001). Despite a preserved mean value of LV ejection fraction (LV EF) in all the groups, subjects in STA group showed a significant reduction of strain in the longitudinal, radial and circumferential directions (p < 0.05 for all). Area strain mean value was also reduced in STA group (p < 0.01). In the overall population, an inverse relationship between longitudinal strain and LV Dd index (r = -0.260, p = 0.008), the E/A ratio (r = -0.249, p = 0.010) and the E' velocity (r = -0.259, p = 0.009) has been identified. Sport-specific patterns of ventricular morphological and functional remodeling are present in athletes performing different kinds of training. 3D-STE is a useful and feasible echocardiographic technique for the assessment of sport-specific pattern of deformational adaptations.
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Atletas , Cardiomegalia Inducida por el Ejercicio , Ecocardiografía Tridimensional , Ventrículos Cardíacos/diagnóstico por imagen , Contracción Miocárdica , Resistencia Física , Función Ventricular Izquierda , Remodelación Ventricular , Adaptación Fisiológica , Adulto , Ciclismo , Fenómenos Biomecánicos , Estudios de Casos y Controles , Estudios Transversales , Ecocardiografía Doppler de Pulso , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Natación , Factores de Tiempo , Adulto JovenRESUMEN
INTRODUCTION: Current guidelines recommend three-dimensional echocardiography (3DE) as the reference technique to assess left ventricular (LV) volumes and ejection fraction (EF). We performed a meta-analysis to identify normative reference values by real time 3DE in healthy subjects. METHODS: We searched MEDLINE and the Cochrane Library databases using the key search terms three-dimensional echocardiography, volumes, and healthy. Data were pooled using random-effects meta-analysis, and source of variation was investigated using meta-regression. After selection, 13 articles were included (2806 subjects). Four studies were conducted in children and young adolescents; one study provided data in an independent pediatric subgroup. RESULTS: In adults, pooled mean value for LV EDV was 98.4 mL (95%CI, 87-110 mL), while LV ESV mean value was 37.0 mL (95%CI, 32-42 mL). LV EF mean value was 62.9% (95%CI 61.7-64.2%). Male subjects showed a significant increase in both LV EDV index (mean difference 5.3 mL/m(2) ; P < 0.001) and LV ESV index (mean difference 3.3 mL/m(2) ; P < 0.001). LV EF was significantly higher in female subjects (P = 0.003). In pediatric studies, LV EDV pooled mean value was 53.1 mL (95%CI, 38.1-68 mL), while for LV ESV, it was 19.8 mL (95%CI, 14.8-24.8 mL); LV EF mean value was 63.3% (95%CI, 61.6-65%). Significant heterogeneity and inconsistency were noted among studies. Age, systolic blood pressure, and heart rate were identified as a source of between-studies variation for LV volumes. Body surface area was a predictor of nonindexed LV volumes. CONCLUSIONS: Data from available studies of normative values for 3DE were summarized. Our findings may increase the generalizability of LV normative data by 3DE.
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Envejecimiento/fisiología , Ecocardiografía Tridimensional/estadística & datos numéricos , Ecocardiografía Tridimensional/normas , Ventrículos Cardíacos/diagnóstico por imagen , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Tamaño Corporal/fisiología , Sistemas de Computación , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/normas , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Factores Sexuales , Adulto JovenRESUMEN
AIMS: Fabry disease (FD) is a rare X-linked genetic disorder caused by the deficiency or absent activity of lysosomal α-galactosidase A. Cardiovascular remodelling is a hallmark of FD. The present study aimed to comprehensively evaluate the cardiac, vascular and microvascular status in a population of patients with genetic mutations for FD without left ventricular hypertrophy (LVH). METHODS AND RESULTS: This study includes subjects carrying genetic mutations for FD (Fabry disease mutation-carrier, FDMC) without LVH (n = 19). A group of control subjects (n = 19) matched for age, sex, body mass index and cardiovascular risk factors were also included. All subjects underwent echocardiography, carotid ultrasound scan, endothelial flow-mediated dilatation (FMD) and nailfold capillaroscopy (NFC) assessment. When compared to the subjects in the control group, FDMC patients showed significantly lower mean values of systolic myocardial velocity (7.33 ± 1.28 vs. 10.08 ± 1.63 cm/s, p < 0.0001), longitudinal systolic strain (-18.07 ± 1.72 vs. -21.15 ± 2.22%, p < 0.0001), significantly higher E/E' mean values (7.15 ± 1.54 vs. 5.98 ± 1.27, p = 0.016) and intima-media thickness mean values (0.80 ± 0.20 vs. 0.61 ± 0.19 mm, p = 0.005), significantly lower FMD (8.3 ± 4.6 vs. 12.2 ± 5.0%, p = 0.02), more atypical capillaries and irregular NFC architecture in FDMC than control subjects (52.6 vs. 0%, p < 0.0001; 78.9 vs. 36.8%, p = 0.02 respectively). CONCLUSIONS: FD progressively involves cardiac, macrovascular and microvascular systems in an early stage. These features are present even in asymptomatic mutation carriers without LVH.
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Enfermedades Cardiovasculares/fisiopatología , Enfermedad de Fabry/genética , Enfermedad de Fabry/fisiopatología , Remodelación Ventricular , Adulto , Índice de Masa Corporal , Enfermedades Cardiovasculares/complicaciones , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Análisis Mutacional de ADN , Ecocardiografía , Enfermedad de Fabry/complicaciones , Femenino , Heterocigoto , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico , Masculino , Microcirculación , Angioscopía Microscópica , Persona de Mediana Edad , Mutación , Riesgo , UltrasonografíaRESUMEN
BACKGROUND: The 2022 ESC Guidelines on Cardio-Oncology recommend baseline cardiovascular risk stratification before starting anticancer drugs, using the new risk assessment tools proposed by the Heart Failure Association (HFA) and the International Cardio-Oncology Society (ICOS).Our study aimed to assess the clinical application of HFA/ICOS risk score in breast cancer patients undergoing chemotherapy and its usefulness in predicting the development of chemotherapy-related cardiac dysfunction (CTRCD). METHODS: A prospective multicentric study enrolled 109 breast cancer patients treated with anthracyclines with or without trastuzumab. A cardiological evaluation, including ECG and echocardiogram at baseline (T0), 3 (T1), 6 (T2), and 12âmonths (T3) after starting treatment was performed. HFA/ICOS score was assessed in all patients. The population was divided into low, medium, high, and very-high risk.During follow-up, CTRCD and other cardiovascular events have been evaluated. RESULTS: 61 patients were low risk, 37 medium, 9 high, 2 very-high risk criteria. We found a significantly higher incidence of overall cardiotoxicity (CTRCD and other cardiovascular events) in the very-high risk group (100%) compared with the medium (29%) and low risk groups (13%). CTRCD incidence was also significantly higher in the high risk group (55%). CTRCD resulted as being associated with baseline arterial hypertension and baseline HFA/ICOS risk score of high ( p â=â0.006) or very-high ( p â<â0.0001). CONCLUSION: Our study confirms the HFA/ICOS score's ability to predict cardiovascular toxicity in breast cancer women and the need for close monitoring especially in high and very-high risk patients.
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Antineoplásicos , Neoplasias de la Mama , Cardiopatías , Insuficiencia Cardíaca , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Estudios Prospectivos , Antineoplásicos/efectos adversos , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Cardiotoxicidad , Proteína Coestimuladora de Linfocitos T InduciblesRESUMEN
Background: The pathophysiological impact of systemic vascular resistance (SVR) and pressure-strain loop-derived global myocardial work index (GWI) in hypertrophic cardiomyopathy (HCM) and transthyretin cardiac amyloidosis (ATTR) has been randomly investigated. Methods: Both SVR and GWI were assessed in outpatients consecutively referred at two Italian cardiology departments for heart failure with preserved left ventricular ejection fraction (LVEF), affected by either nonobstructive HCM or wild-type ATTR. Based on relevant cross-tabulations, the patients were gathered into 4 functional classes according to cut-off values of 1440 dyne/s/cm-5 for SVR, and 1576 mm Hg% for GWI, as suggested by previous studies. Results: A total of 60 patients, 30 in each group, aged 61 ± 16 years, with 78% males, were studied. HCM patients were younger than those with ATTR and in a better clinical condition (23% HCM vs. 77% ATTR were NYHA class II-III, p < 0.001). Overall, 51 patients (85%) showed a high SVR, 21/30 HCM (70%), and 30 ATTR (100%) (p < 0.005). Both SVR and GWI (expressions of ventricular-arterial coupling) were impaired in 43% of HCM patients (showing greater LV concentric hypertrophy) and 93% of ATTR patients (in advanced NYHA functional class) (p < 0.001). Conclusions: A substantial percentage of present study population showed impaired SVR and/or GWI, despite preserved LVEF. The proposed classification may shed further light on the pathophysiological and clinical characteristics of such hypertrophic phenotypes.
RESUMEN
In recent years, important advances have been made in the field of Cardio-Oncology. The 2022 ESC Guidelines on Cardio-Oncology proposed a baseline cardiovascular risk stratification for cancer patients and preventive strategies in patients at high and very-high risk of cardiotoxicity. Cardiovascular toxic effects of anti-cancer drugs are being extensively studied; surveillance programs have been proposed, based on the baseline cardiovascular risk. On the other hand, there is little data on Cardio-Oncological management of patients at high and very-high cardiovascular risk with previous cardiovascular diseases. For example, little is known about management of cancer patients with heart failure with reduced ejection fraction (HFrEF), patients with a recent myocardial infarction or other cardiovascular diseases; when to resume anti-cancer drugs after a cardiovascular toxic event. Collaboration between Cardiologists and Oncologists and multidisciplinary team evaluations are certainly essential to decide the best therapeutic strategy for cancer patients, to treat cancer while saving the heart. Therefore, in the present review, we attempt to provide a useful guide to clinicians in treating patients with high and very-high risk of cardiotoxicity by enucleating main questions and answering them based on the evidence available as well as expert opinion and our clinical experience.
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Antineoplásicos , Insuficiencia Cardíaca , Neoplasias , Disfunción Ventricular Izquierda , Humanos , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/tratamiento farmacológico , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Volumen Sistólico , Neoplasias/tratamiento farmacológico , Neoplasias/inducido químicamente , Antineoplásicos/efectos adversos , Disfunción Ventricular Izquierda/inducido químicamenteRESUMEN
AIM: To evaluate the association between raphe in bicuspid aortic valve (BAV) patients and valve dysfunction, aortopathy and aortic valve surgery in the REBECCA registry [REgistro della valvola aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging (SIECVI)]. METHODS: Prevalence of aortic valve dysfunction and aortopathy was investigated in BAV patients with and without raphe. Aortic valve dysfunction (regurgitation or stenosis) was categorized as mild, moderate and severe. Aortopathy was defined as annulus ≥14 mm/m2; root ≥20 mm/m2; sinotubular junction ≥16 mm/m2; ascending aorta ≥17 mm/m2, and classified in Type A, isolated ascending aorta dilatation; Type B, aortic root and ascending aorta dilatation; and Type C, isolated aortic root dilatation. RESULTS: Overall, 695 patients with BAV were enrolled; 520 (74.8%) with raphe and 175 (25.2%) without raphe. BAV patients with raphe presented more frequently with moderate or severe aortic stenosis than BAV patients without raphe (183 [35.2%] vs 34 [19.4%], p < 0.001). A higher prevalence of aortopathy, particularly Type B, was observed in patients with vs without raphe. At multivariable analysis, raphe was a predictor of aortic valve surgery at three-year follow-up (odds ratio 2.19, 95% confidence interval 1.08-4.44, p < 0.001). CONCLUSIONS: Patients with BAV and raphe have a higher prevalence of significant aortic stenosis, aortopathy, especially Type B, and a higher risk of undergoing aortic valve surgery at three-year follow-up.
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Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Enfermedades de las Válvulas Cardíacas , Sistema de Registros , Humanos , Masculino , Femenino , Enfermedad de la Válvula Aórtica Bicúspide/cirugía , Enfermedad de la Válvula Aórtica Bicúspide/diagnóstico por imagen , Enfermedad de la Válvula Aórtica Bicúspide/complicaciones , Persona de Mediana Edad , Válvula Aórtica/anomalías , Válvula Aórtica/cirugía , Válvula Aórtica/diagnóstico por imagen , Anciano , Enfermedades de las Válvulas Cardíacas/cirugía , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de la Aorta/cirugía , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/epidemiología , Adulto , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estudios de Seguimiento , Italia/epidemiologíaRESUMEN
Aims: Hypertrophic cardiomyopathies (HCM) are caused in 30-60% of cases by mutations in cardiac sarcomere genes but can also be an expression of cardiac involvement in multi-systemic metabolic diseases, such as Anderson-Fabry disease (AFD). HCM entails a risk of sudden cardiac death (SCD) of 0.9%/year and is the most common cause of SCD in young adults. Recent studies suggested mechanical dispersion (MD) by speckle tracking echocardiography (STE) as an additional arrhythmic risk marker. The aim of the study was to evaluate left ventricle global longitudinal strain (LV-GLS) and MD, in patients with HCM or AFD cardiomyopathy, and the association with ventricular arrhythmias (V-AR). Methods and results: We evaluated 40 patients with HCM, 57 with AFD (12 with LV hypertrophy and 45 without), and 40 healthy subjects, between January 2014 and June 2022. We performed a comprehensive echocardiographic study and analysed systolic and diastolic functions, LV-GLS, and MD. We also analysed V-AR, including ventricular fibrillation and sustained/non-sustained ventricular tachycardia, by Holter electrocardiogram (Holter-EKG), in a subset of hypertrophic patients. Data were analysed by unpaired Student t-test or chi-square/Fisher's exact test as appropriate and binary logistic regression (SPSS Statistics ver.26). LV-GLS was significantly lower in the V-AR group compared with patients without V-AR (median -10.2% vs. -14%, P = 0.038); MD was significantly higher in the V-AR group (85.5â ms vs. 61.1â ms, P = 0.004). V-AR were found significantly associated with MD (OR, 1.030; 95% CI, 1.003-1.058; P = 0.03). Conclusions: MD is a useful additional index in the evaluation of patients with HCM and may be a promising prognostic predictor of increased arrhythmic risk.
RESUMEN
Anderson-Fabry Disease (AFD) is a rare, systemic lysosomal storage disease triggered by mutations in the GLA gene, leading to α-galactosidase A (α-Gal A) deficiency. The disease's X-linked inheritance leads to more severe, early-onset presentations in males, while females exhibit variable, often insidious, manifestations, notably impacting cardiac health. This study aims to examine gender-based AFD cardiac manifestations in correlation with the variant type: classical (CL), late-onset (LO), or variants of uncertain significance (VUS). We analyzed data from 72 AFD patients (53 females, 19 males) referred to the "G. Rodolico" University Hospital, employing enzyme activity measurements, genetic analysis, periodic lyso-Gb3 monitoring, comprehensive medical histories, and advanced cardiac imaging techniques. Statistical analysis was performed using SPSS version 26. Our AFD cohort, with an average age of 45 ± 16.1 years, comprised 12 individuals with hypertrophy (AFD-LVH) and 60 without (AFD-N). Women, representing about 75% of the subjects, were generally older than men (47.2 ± 16.2 vs. 38.8 ± 14.6, p = 0.046). In the female group, 17% had CL variants, 43.3% LO, and 39.6% had VUS, compared to 21.1%, 36.8%, and 31.6% in the male group, respectively. Females exhibited significantly higher α-Gal A values (median 7.9 vs. 1.8 nmol/mL/h, p < 0.001) and lower lyso-Gb3 levels (1.5 [IQR 1.1-1.7] vs. 1.9 [1.5-17.3] nmol/L, p = 0.02). Regarding the NYHA class distribution, 70% of women were in class I and 28% in class II, compared to 84% and 16% of men, respectively. Among women, 7.5% exhibited ventricular arrhythmias (10.5% in men), and 9.4% had atrial fibrillation (10.5% in men). Cardiac MRIs revealed fibrosis in 57% of examined women, compared to 87% of men. Even among patients without LVH, significant differences persisted in α-Gal A and lyso-Gb3 levels (p = 0.003 and 0.04), as well as LVMi (61.5 vs. 77.5 g/sqm, p = 0.008) and GLS values (-20% vs. -17%, p = 0.01). The analysis underscored older age, decreased lyso-Gb3 deposition, reduced hypertrophy, and lesser GLS compromise in females, suggesting later disease onset. Severe cardiac patterns were associated with classic variants, while more nuanced manifestations were noted in those with VUS. Early GLS impairment in males, irrespective of hypertrophy, emphasized the role of subclinical damage in AFD.
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Cardiomiopatías , Enfermedad de Fabry , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Caracteres Sexuales , Enfermedad de Fabry/diagnóstico por imagen , Enfermedad de Fabry/genética , alfa-Galactosidasa/genética , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/genética , Cardiomiopatías/complicaciones , Hipertrofia/complicacionesRESUMEN
BACKGROUND: Clinically, there is considerable heterogeneity in the presentation of transthyretin amyloidosis (ATTR), which ranges from primarily cardiac and primarily neurologic to mixed disease, among other manifestations. Because of this complex presentation, the diagnosis and management of patients with ATTR are often challenging and should be performed in interdisciplinary centers specialized in amyloidosis. Here, we aimed to increase awareness of ATTR detection and pathophysiology through a multidimensional multiorgan approach. CASE REPORT: We reported on a 60-year-old man with wild-type ATTR who underwent a number of both basic and advanced cardiological and neurological investigations at baseline and after a treatment period with the TTR tetramer stabilizer, tafamidis. Several findings are provided here, some of which might be considered instrumental correlates of the patient's clinical improvement after therapy. CONCLUSIONS: Adequate awareness and prompt recognition of ATTR support early diagnosis and faster access to therapies, thereby slowing the progression and improving the prognosis. The need for a multidisciplinary alliance between specialists and the opportunity to perform, at least in selected cases, a set of specific examinations for a detailed assessment of ATTR patients can also provide valuable insights into the physiopathology and response to therapy of a disease as complex and intriguing as ATTR.
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Background: Left atrial (LA) function is crucial for assessing left ventricular filling in various cardiovascular conditions. Cardiac Amyloidosis (CA) is characterized by atrial myopathy and LA function impairment, with diastolic dysfunction up to restrictive filling pattern, leading to progressive heart failure and arrhythmias. This study evaluates LA function and deformation using speckle tracking echocardiography (STE) in patients with CA compared to a cohort of patients with sarcomeric Hypertrophic Cardiomyopathy (HCM) and a control group. Methods: We conducted a retrospective, observational study (from January 2019 to December 2022) including a total of 100 patients: 33 with ATTR-CA, 34 with HCMs, and 33 controls. Clinical evaluation, electrocardiograms, and transthoracic echocardiography were performed. Echocardiogram images were analyzed in post-processing using EchoPac software for LA strain quantification, including LA-reservoir, LA-conduit, and LA-contraction strain. Results: The CA group exhibited significantly impaired LA function compared to HCMs and control groups, with LA-reservoir median values of -9%, LA-conduit -6.7%, and LA-contraction -3%; this impairment was consistent even in the CA subgroup with preserved ejection fraction. LA strain parameters correlated with LV mass index, LA volume index, E/e', and LV-global longitudinal strain and were found to be associated with atrial fibrillation and exertional dyspnea. Conclusions: LA function assessed by STE is significantly impaired in CA patients compared to HCMs patients and healthy controls. These findings highlight the potential supportive role of STE in the early detection and management of the disease.
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Global left ventricular (LV) myocardial work (MW) indexes can be recognized at ultrasound imaging from the LV pressure/global longitudinal strain (GLS) loop analysis. A total of 4 indexes, global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), have been demonstrated to overcome the methodological limitations of GLS and provide useful information on myocardial dysfunction in some clinical settings. Although impaired MW indexes have been demonstrated in patients with transthyretin cardiac amyloidosis (ATTR) or with nonobstructive hypertrophic cardiomyopathy (HCM), there are no comparative studies at present. This study aimed to describe the characteristics of MW in both these clinical settings compared with patients with well-controlled hypertension (HTN). A total of 83 patients, 32 with ATTR (aged 70 ± 11 years, 32% mutated, 68% wild-type, 72% men), 29 with HCM (aged 57 ± 17 years), and 22 HTN controls (aged 56 ± 5.6 years, 59% men) were prospectively enrolled at 2 clinical centers. All participants had New York Heart Association class I or II. Overall, the LV mass index was greater in both study groups than in HTN, whereas the LV ejection fraction (EF) was significantly lower in ATTR compared with other groups. Based on this finding, patients with ATTR were further divided into 2 subgroups: ATTR1 (LVEF ≤0.50), n = 14 (44%) and ATTR2 (LVEF >0.50), n = 18 (56%). Overall, the GWI and GCW were lower in all ATTR patients (mostly in ATTR1) than in the other groups (p <0.001), whereas only small differences in GWE and none in GWW were found among the groups. Of interest, the pairwise comparison and receiver operating characteristic analysis in preserved LVEF patients showed that GWI was a better discriminator of ATTR2 from HCM patients than GLS, with the cut-off value ≤1,419 mm Hg% (89% sensitivity; 55% specificity; p = 0.013). In conclusion, MW analysis was confirmed to be a modern way to investigate myocardial function in patients with hypertrophic phenocopies. GWI and GCW were more impaired in patients with ATTR compared with HCM and HTN controls. Furthermore, this study likely revealed an additional discriminative value of GWI over GLS alone in preserved LVEF settings.
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Amiloidosis , Cardiomiopatía Hipertrófica , Hipertensión , Masculino , Humanos , Femenino , Prealbúmina , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Miocardio , Tensión Longitudinal Global , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
INTRODUCTION: Heart rate variability (HRV) indicates the temporal fluctuation of the intervals between adjacent beats. HRV expresses neuro-cardiac activity and is generated by heart-brain interactions and dynamics related to the function of the autonomous nervous system and other components. To investigate this issue, we started a series of experiments by coupling the flight tasks of student pilots and their HRV.METHODS: Before each experimental session, the participating student was fitted with a five-electrode, three-channel Holter electrocardiogram monitor. We defined three time-phases for each training mission: before flight operations on the ground, during flight operations, and after flight operations on the ground. The HRV analysis was performed by quantifying some indices of the time domain and the frequency domain.RESULTS: The analysis of RR-wave intervals revealed two types of trends: 1) students whose RR intervals decreased during flight operations compared to before flight ground operations; and 2) students whose RR intervals increased during flight operations compared to before flight ground operations. These differences found in the RR intervals produced changes in the indices of both the time and frequency domains of the two students' samples.DISCUSSION: Flight training involves regular and advanced tasks and/or emergency situations. When this happens, the total power of the heart decreases because the RR intervals are forced toward low values. Flight activity involves continuous demanding tasks that can be potentially read by an analysis of the HRV; a high HRV ensures better management of tasks that require a greater commitment of cardiovascular function.Li Volsi G, Monte IP, Aruta A, Gulizzi A, Libra A, Mirulla S, Panebianco G, Patti G, Quattrocchi F, Bellantone V, Castorina W, Arcifa S, Papale F. Heart rate variability indices of student pilots undergo modifications during flight training. Aerosp Med Hum Perform. 2023; 94(11):835-842.
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Corazón , Pilotos , Humanos , Frecuencia Cardíaca/fisiología , Electrocardiografía , EstudiantesRESUMEN
BACKGROUND: Heart rate (HR) indicates the number of beats per minute (bpm) of the heart, while heart rate variability (HRV) indicates the temporal fluctuation of the intervals between adjacent beats (NN). HRV expresses neuro-cardiac activity and is generated by heart-brain interactions and dynamics related to the function of the autonomic nervous system (ANS) and other components (e.g., body and ambient temperature, respiration, hormones, blood pressure). We are carrying out a series of experimental investigations with the aim of studying HRV in student pilots during training.CASE REPORT: For this purpose, we used a Holter electrocardiograph equipped with three channels and five electrodes positioned on the chest of the subject who participated in our investigation. The case report refers to a student pilot who, during a flight mission with the instructor, had to face a forced landing and a flap failure. We report data based on analysis of the time domain and frequency domain related to operations on the ground before the flight, during the flight, and on the ground after the flight.DISCUSSION: Our initial conclusion is that the extent of HRV constitutes an "energy store" for better cardiac performance in eustress activities. During advanced tasks, the "Total Power" of the heart decreases because the RR intervals are forced toward low values, where the heart is less able to be modulated by its many controllers. Furthermore, this experimental protocol can be useful to flight instructors for the training process of student pilots.Li Volsi G, Monte IP, Aruta A, Gulizzi A, Libra A, Mirulla S, Panebianco G, Patti G, Quattrocchi F, Bellantone V, Castorina W, Arcifa S, Papale F. Heart rate variability of a student pilot during flight training. Aerosp Med Hum Perform. 2023; 94(6):475-479.