11 research outputs found
Clinical findings and prognosis of Danon’s Disease. An analysis from the Spanish multicenter Danon Registry.
Introducción y objetivos:
La enfermedad de Danon (ED) es una enfermedad poco frecuente producida por mutaciones en el gen LAMP2. Se considera una enfermedad multisistémica caracterizada por: miocardiopatía hipertrófica con preexcitación y gran hipertrofia, discapacidad intelectual, miopatía, presentación infantil y peor pronóstico en varones. Existen pocas series que permitan conocer las características clínicas y el pronóstico de la ED en detalle.
Métodos
Estudio retrospectivo basado en el análisis de los registros clínicos de los pacientes con ED seguidos en 10 hospitales españoles.
Resultados
Se incluyeron 28 pacientes (3220años, 79% mujeres). Los varones demostraron una elevada prevalencia de manifestaciones extracardiacas: miopatía (80%), trastornos del aprendizaje (83%) y alteraciones visuales (60%), siendo hallazgos infrecuentes en las mujeres (5%, 0% y 24%, respectivamente). Aunque la miocardiopatía hipertrófica era la cardiopatía más habitual (67%), el grosor máximo ventricular fue 157 mm y 12 pacientes (10 mujeres) se presentaron con miocardiopatía dilatada. Sólo 11 pacientes (46%) (4 hombres y 7 mujeres) mostraron preexcitación y en 16 (67%) la enfermedad debutó por encima de los 20 años. Tras una mediana de seguimiento de 4 años (P25-752-9), 4 varones (67%) y 9 mujeres (41%) fallecieron o requirieron un trasplante. Tanto la afectación cardiaca como los eventos adversos ocurrieron más tardíamente en mujeres (37±9 vs 23±16 y 38±21 vs 20±11 años, respectivamente).
Conclusiones.
Las características clínicas de la ED difieren substancialmente de lo tradicionalmente considerado. La edad de presentación de la ED es más tardía, no se expresa como una patología multisistémica en mujeres y la preexcitación es poco frecuente. Aunque las mujeres presentan mal pronóstico, los eventos adversos ocurren a una edad más avanzada.Background
Danon's disease (DD) is a rare disease caused by mutations in the LAMP2 gene. It is considered a multisystemic disease characterized by: hypertrophic cardiomyopathy with preexcitation and ventricular hypertrophy, intellectual disability, myopathy, childhood presentation and worse prognosis in men. Available data regarding clinical characteristics and the prognosis of the DD are scarce.
Methods
Retrospective study based on the analysis of the clinical records of patients with ED from 10 Spanish hospitals.
Results
Twenty-eight patients were included (32±20 years, 79% women). Males showed a high prevalence of extracardiac manifestations: myopathy (80%), learning disorders (837%) and visual alterations (60%), which were uncommon findings in women (5%, 0% and 24%, respectively). Although hypertrophic cardiomyopathy was the most common form of heart disease (67%), maximum wall thickness was 15±7 mm and 12 patients (10 women) presented as dilated cardiomyopathy. Only 11 patients (467%) (4 men and 7 women) showed preexcitation and in 16 (67%) the disease started above 20 years-old. After a median follow-up of 4 years (P25-75: 2-9), 4 men (67%) and 9 women (41%) died or required a heart transplant. Both cardiac involvement and adverse events occurred later in women (37 ± 9 vs 23 ± 16 and 38± 21 vs 20 ± 11 years, respectively).
Conclusions
Clinical characteristics of DD differ substantially from what has been traditionally considered. ED usually presents at an increased age, is not a multisystemic disease in women and preexcitation is rare. Even though, women show also a poor prognosis, adverse events occur at a later age.pre-print518 K
Impact of SARS-Cov-2 infection in patients with hypertrophic cardiomyopathy : results of an international multicentre registry
To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12-4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75-9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16-26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20-49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98-2.91, P = 0.0600). Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality
Natural History of MYH7-Related Dilated Cardiomyopathy
BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation
Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world
Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.
Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.
Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.
Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis.
Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection
Seguridad del MitraClip en pacientes con cable endocárdico de resincronización cardiaca en el ventrículo izquierdo a través del septo interventricular
Natural History of MYH7-related Dilated Cardiomyopathy
Background
Variants in MYH7 are responsible for disease in 1-5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described.
Objectives
We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression.
Methods
We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% females, 35.6±19.2 years) recruited from 29 international centers.
Results
At initial evaluation, 106 patients (72.1%) had DCM (LVEF 34.5±11.7%). Median follow-up was 4.5 years (interquartile range: 1.7-8.0) and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years. Thirty-six percent of patients with DCM met imaging criteria for LV non-compaction. During follow-up, 28% showed left ventricular reverse remodeling (LVRR). Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths due to end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia (MVA) rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF?35%, respectively). ESHF and MVA were significantly lower compared with LMNA-related DCM and similar than in DCM caused by TTN truncating variants.
Conclusions
MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low LVRR, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.Funding: This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects "PI18/0004, PI20/0320, PT17/0015/0043” (Co-funded by European Regional Development Fund/European Social Fund "A way to make Europe"/"Investing in your future"). The CNIC is supported by the ISCIII, MCIN, the Pro-CNIC Foundation, and the Severo Ochoa Centers of Excellence program (CEX2020-001041-S). The Hospital Universitario Puerta de Hierro, the Hospital Sant Joan de Déu and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart: ERN GUARD-Heart (http://guardheart.ernnet.eu). Fernando de Frutos receives grant support from ISCIII (CM20/00101). Annette Baas receives funding from CVON2020B005 DOUBLE-DOSE, Dutch Heart Foundation (Dekker 2015T041). Genetic examinations of Polish patients were funded with DETECTIN-HF grant from ERA-CVD framework, NCBiR. Diane Fatkin receives funding from Victor Chang Cardiac Research Institute and NSW Health. Luis R Lopes is funded by an MRC UK Clinical Academic Research Partnership award (MR/T005181/1). Benjamin Meder receives funding from the Deutsches Zentrum für Herz-Kreislauf-Forschung (German Center for Cardiovascular Research, DZHK) and Informatics for Life (Klaus Tschira Foundation). Milos Kubankek receives grant support from the Ministry of Health, Czech Republic (NV19-08-00122) and IPO (Institute for Clinical and Experimental Medicine – IKEM, IN 00023001)
Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction
Less than 40% of patients with dilated cardiomyopathy (DCM) have a pathogenic/likely pathogenic genetic variant identified. TBX20 has been linked to congenital heart defects; although an association with left ventricular noncompaction (LVNC) and DCM has been proposed, it is still considered a gene with limited evidence for these phenotypes. This study sought to investigate the association between the TBX20 truncating variant (TBX20tv) and DCM/LVNC. TBX20 was sequenced by next-generation sequencing in 7463 unrelated probands with a diagnosis of DCM or LVNC, 22 773 probands of an internal comparison group (hypertrophic cardiomyopathy, channelopathies, or aortic diseases), and 124 098 external controls (individuals from the gnomAD database). Enrichment of TBX20tv in DCM/LVNC was calculated, cosegregation was determined in selected families, and clinical characteristics and outcomes were analyzed in carriers. TBX20tv was enriched in DCM/LVNC (24/7463; 0.32%) compared with internal (1/22 773; 0.004%) and external comparison groups (4/124 098; 0.003%), with odds ratios of 73.23 (95% CI, 9.90-541.45; P <0.0001) and 99.76 (95% CI, 34.60-287.62; P <0.0001), respectively. TBX20tv was cosegregated with DCM/LVNC phenotype in 21 families for a combined logarythm of the odds score of 4.53 (strong linkage). Among 57 individuals with TBX20tv (49.1% men; mean age, 35.9±20.8 years), 41 (71.9%) exhibited DCM/LVNC, of whom 14 (34.1%) had also congenital heart defects. After a median follow-up of 6.9 (95% CI, 25-75:3.6-14.5) years, 9.7% of patients with DCM/LVNC had end-stage heart failure events and 4.8% experienced malignant ventricular arrhythmias. TBX20tv is associated with DCM/LVNC; congenital heart defect is also present in around one-third of cases. TBX20tv -associated DCM/LVNC is characterized by a nonaggressive phenotype, with a low incidence of major cardiovascular events. TBX20 should be considered a definitive gene for DCM and LVNC and routinely included in genetic testing panels for these phenotypes
Impact of SARS‐Cov‐2 infection in patients with hypertrophic cardiomyopathy: results of an international multicentre registry
Abstract Aims To describe the natural history of SARS‐CoV‐2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. Methods and results Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS‐Cov‐2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS‐CoV‐2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty‐nine (22.9%) HCM patients were hospitalized for non‐ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS‐CoV‐2‐related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12–4.51], P = 0.0229}, baseline New York Heart Association class [OR per one‐unit increase 4.01 (95%CI: 1.75–9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16–26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20–49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community‐based SARS‐CoV‐2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98–2.91, P = 0.0600). Conclusions Over one‐fourth of HCM patients infected with SARS‐Cov‐2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality
Reduction of cardiac imaging tests during the COVID-19 pandemic: The case of Italy. Findings from the IAEA Non-invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID)
Background: In early 2020, COVID-19 massively hit Italy, earlier and harder than any other European country. This caused a series of strict containment measures, aimed at blocking the spread of the pandemic. Healthcare delivery was also affected when resources were diverted towards care of COVID-19 patients, including intensive care wards. Aim of the study: The aim is assessing the impact of COVID-19 on cardiac imaging in Italy, compare to the Rest of Europe (RoE) and the World (RoW). Methods: A global survey was conducted in May–June 2020 worldwide, through a questionnaire distributed online. The survey covered three periods: March and April 2020, and March 2019. Data from 52 Italian centres, a subset of the 909 participating centres from 108 countries, were analyzed. Results: In Italy, volumes decreased by 67% in March 2020, compared to March 2019, as opposed to a significantly lower decrease (p < 0.001) in RoE and RoW (41% and 40%, respectively). A further decrease from March 2020 to April 2020 summed up to 76% for the North, 77% for the Centre and 86% for the South. When compared to the RoE and RoW, this further decrease from March 2020 to April 2020 in Italy was significantly less (p = 0.005), most likely reflecting the earlier effects of the containment measures in Italy, taken earlier than anywhere else in the West. Conclusions: The COVID-19 pandemic massively hit Italy and caused a disruption of healthcare services, including cardiac imaging studies. This raises concern about the medium- and long-term consequences for the high number of patients who were denied timely diagnoses and the subsequent lifesaving therapies and procedures
International Impact of COVID-19 on the Diagnosis of Heart Disease
Background: The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. Objectives: The study sought to assess COVID-19's impact on global cardiovascular diagnostic procedural volumes and safety practices. Methods: The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. Results: Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower–middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth. Conclusions: COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19–related changes in care delivery is warranted