RESUMEN
BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.
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Cardiomiopatía Dilatada , Medicina de Precisión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Población Negra , Cardiomiopatía Dilatada/epidemiología , Cardiomiopatía Dilatada/etnología , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/terapia , Desfibriladores Implantables , Evaluación de Medicamentos , Adulto , Anciano , Blanco , Negro o Afroamericano , Estados Unidos/epidemiologíaRESUMEN
Importance: Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. Objective: To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. Design: Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. Exposure: Presence of DCM. Main Outcomes and Measures: Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). Results: A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, -0.09 [95% CI, -0.14 to -0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, -0.06 [95% CI, -0.11 to -0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, -0.07 [95% CI, -0.22 to 0.09]) due to a larger number of non-TTN non-predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P < .001). Conclusion and Relevance: Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.
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Indio Americano o Nativo de Alaska , Población Negra , Cardiomiopatía Dilatada , Hispánicos o Latinos , Población Blanca , Humanos , Indio Americano o Nativo de Alaska/genética , Población Negra/genética , Cardiomiopatía Dilatada/etnología , Cardiomiopatía Dilatada/genética , Estudios Transversales , Genómica , Hispánicos o Latinos/genética , Población Blanca/genéticaRESUMEN
BACKGROUND: Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD). OBJECTIVES: This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients. METHODS: Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results. RESULTS: A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM. CONCLUSIONS: Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs.
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Cardiomiopatía Dilatada , Femenino , Humanos , Masculino , Población Negra , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/genética , Ecocardiografía , Etnicidad , Hispánicos o Latinos , Hipertrofia Ventricular Izquierda , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive. METHODS: The DCM Precision Medicine Study developed Family Heart Talk, a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive the day after proband enrollment and not enrolled on the same day as the proband. RESULTS: Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08-∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P=0.90). CONCLUSIONS: Family Heart Talk, a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.
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Cardiomiopatía Dilatada , Humanos , Cardiomiopatía Dilatada/diagnóstico , Etnicidad , Familia , Salud de la Familia , Medición de RiesgoRESUMEN
Importance: Cardiovascular disease contributes outsized mortality in patients from underrepresented racial and ethnic groups. Understanding levels of trust in medical researchers and knowledge of genome sequencing may help identify barriers to research participation and develop strategies to educate patients about the role of genetics in cardiovascular disease. Objective: To assess racial and ethnic differences in trust in medical researchers and genome-sequencing knowledge among patients with idiopathic dilated cardiomyopathy and determine the association between trust in medical researchers and genome-sequencing knowledge. Design, Setting, and Participants: This cross-sectional study conducted by a consortium of 25 US heart failure programs included patients with idiopathic dilated cardiomyopathy defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes. Enrollment occurred from June 7, 2016, to March 15, 2020. Main Outcomes and Measures: Percent distributions, means, and associations of genome-sequencing knowledge scores and research trust scores for Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White participants (hereafter referred to as White). Results: Among 1121 participants, mean (SD) age was 51.6 (13.6) years with 41.4% Black, 8.5% Hispanic, and 43.4% female. After accounting for site effects, the level of genome-sequencing knowledge was lower in Hispanic and Black participants compared with White participants (mean score difference, -2.6; 95% CI, -3.9 to -1.2 and mean score difference, -2.9; 95% CI, -3.6 to -2.2, respectively). The level of trust in researchers was lowest in Black participants (mean score, 27.7), followed by Hispanic participants (mean score, 29.4) and White participants (mean score, 33.9). Racial and ethnic differences remained after adjusting for education, age at enrollment, duration of dilated cardiomyopathy, and health status. A higher level of trust was associated with a higher level of genome-sequencing knowledge within different racial and ethnic groups. Conclusions and Relevance: In this cross-sectional study, large racial and ethnic differences in levels of genome-sequencing knowledge and trust in medical researchers were observed among patients with dilated cardiomyopathy. Findings from this study can inform future studies that aim to enhance the uptake of genomic knowledge and level of trust in medical researchers.
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Cardiomiopatía Dilatada , Etnicidad , Humanos , Femenino , Persona de Mediana Edad , Masculino , Etnicidad/genética , Cardiomiopatía Dilatada/genética , Confianza , Estudios Transversales , Consentimiento InformadoRESUMEN
BACKGROUND: Continuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients. METHODS: We retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing). RESULTS: Between 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1-2114] vs 68 [1-690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43-0.86); Pâ¯=â¯0.005), ventricular arrhythmias (HR 0.34 [0.15-0.74]; Pâ¯=â¯0.007) and ICD therapies (HR 0.24 [0.07-0.79]; Pâ¯=â¯0.02). CONCLUSION: In patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias.
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Insuficiencia Cardíaca , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Arritmias Cardíacas , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Importance: Idiopathic dilated cardiomyopathy (DCM) aggregates in families, and early detection in at-risk family members can provide opportunity to initiate treatment prior to late-phase disease. Most studies have included only White patients, yet Black patients with DCM have higher risk of heart failure-related hospitalization and death. Objective: To estimate the prevalence of familial DCM among DCM probands and the age-specific cumulative risk of DCM in first-degree relatives across race and ethnicity groups. Design, Setting, and Participants: A family-based, cross-sectional study conducted by a multisite consortium of 25 US heart failure programs. Participants included patients with DCM (probands), defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes, and their first-degree relatives. Enrollment commenced June 7, 2016; proband and family member enrollment concluded March 15, 2020, and April 1, 2021, respectively. Exposures: The presence of DCM in a proband. Main Outcomes and Measures: Familial DCM defined by DCM in at least 1 first-degree relative; expanded familial DCM defined by the presence of DCM or either left ventricular enlargement or left ventricular systolic dysfunction without known cause in at least 1 first-degree relative. Results: The study enrolled 1220 probands (median age, 52.8 years [IQR, 42.4-61.8]; 43.8% female; 43.1% Black and 8.3% Hispanic) and screened 1693 first-degree relatives for DCM. A median of 28% (IQR, 0%-60%) of living first-degree relatives were screened per family. The crude prevalence of familial DCM among probands was 11.6% overall. The model-based estimate of the prevalence of familial DCM among probands at a typical US advanced heart failure program if all living first-degree relatives were screened was 29.7% (95% CI, 23.5% to 36.0%) overall. The estimated prevalence of familial DCM was higher in Black probands than in White probands (difference, 11.3% [95% CI, 1.9% to 20.8%]) but did not differ significantly between Hispanic probands and non-Hispanic probands (difference, -1.4% [95% CI, -15.9% to 13.1%]). The estimated prevalence of expanded familial DCM was 56.9% (95% CI, 50.8% to 63.0%) overall. Based on age-specific disease status at enrollment, estimated cumulative risks in first-degree relatives at a typical US advanced heart failure program reached 19% (95% CI, 13% to 24%) by age 80 years for DCM and 33% (95% CI, 27% to 40%) for expanded DCM inclusive of partial phenotypes. The DCM hazard was higher in first-degree relatives of non-Hispanic Black probands than non-Hispanic White probands (hazard ratio, 1.89 [95% CI, 1.26 to 2.83]). Conclusions and Relevance: In a US cross-sectional study, there was substantial estimated prevalence of familial DCM among probands and modeled cumulative risk of DCM among their first-degree relatives. Trial Registration: ClinicalTrials.gov Identifier: NCT03037632.
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Cardiomiopatía Dilatada/epidemiología , Salud de la Familia/estadística & datos numéricos , Grupos Raciales/estadística & datos numéricos , Adulto , Factores de Edad , Población Negra/estadística & datos numéricos , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/etnología , Intervalos de Confianza , Estudios Transversales , Diagnóstico Precoz , Salud de la Familia/etnología , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/etnología , Masculino , Persona de Mediana Edad , Prevalencia , Grupos Raciales/etnología , Riesgo , Estados Unidos/epidemiología , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/etnología , Población Blanca/estadística & datos numéricosRESUMEN
OBJECTIVES: The influence of preoperative left ventricular size in outcomes following centrifugal-flow left ventricular assist device (LVAD) implantation has not been well characterized. METHODS: A cohort of 313 patients who received a centrifugal-flow LVAD at a single institution was analysed. Using a maximally selected log-rank statistic, we investigated whether a left ventricular end-diastolic dimension (LVEDD) cut-off point was associated with worse outcomes. The cohort was then divided in 2 groups based on the LVEDD cut-off point. RESULTS: An LVEDD cut-off point of 59 mm was found to predict worse survival. Smaller LVEDD patients (≤59 mm, N = 52) were older and more likely to have a history of coronary artery disease compared those with a larger LVEDD (>59 mm, N = 261). Smaller LVEDD patients had lower survival compared to larger LVEDD patients (71% vs 85% at 1 year and 58% vs 80% at 2 years, P = 0.003). The need for temporary right ventricular mechanical support was significantly higher in the smaller LVEDD cohort (11.5% vs 1.9%, P = 0.002). Pump flows at time of discharge were lower in the smaller LVEDD group (3.8 vs 4.2 l/min, P = 0.005), who also had a higher incidence of late right ventricular failure (23% vs 12%, P = 0.02), higher rates of gastrointestinal bleeding (0.416 vs 0.256 events per patient-year, P = 0.025) and higher readmissions secondary to low flow alarms (0.429 vs 0.240 events per patient-year, P = 0.007). Multivariable analysis demonstrated that smaller LVEDD, older age, high BUN and high bilirubin levels were independent predictors of worse survival. CONCLUSIONS: In patients receiving a centrifugal-flow LVAD, smaller preoperative LVEDD (≤59 mm) was associated with lower survival and higher incidence of adverse outcomes.
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Insuficiencia Cardíaca , Corazón Auxiliar , Procedimientos Quirúrgicos Torácicos , Estudios de Cohortes , Ventrículos Cardíacos , Corazón Auxiliar/efectos adversos , Humanos , Estudios RetrospectivosRESUMEN
BACKGROUND: Due to anatomic and physiologic concerns, prior generations of the left ventricular assist devices (LVAD) have frequently been denied to patients with small body size. However, outcomes in patients with small body surface area (BSA) following HeartMate 3 (HM3) LVAD implantation remain relatively unknown. METHODS: A cohort of 220 patients implanted at a single center was divided into two groups: BSA ≤1.8 m2 (small BSA, n = 37) and BSA >1.8 m2 (large BSA, n = 183). We investigated baseline characteristics and clinical outcomes including survival and incidence of adverse events. RESULTS: Small BSA patients were older (60 vs. 57 years), more likely female (60% vs. 20%), had a lower body mass index (24 vs. 32 kg/m2 ), lower incidence of diabetes (32% vs. 51%), history of stroke (5% vs. 19%), and left ventricular thrombus (0% vs. 11%). They had smaller left ventricular end diastolic diameter (64.8 vs. 69.3 mm). Pump speed and pump flows at discharge were lower in the small BSA group. Survival at 1 year and 2 years was 86% versus 87% and 86% versus 79% for small versus large BSA groups (p = 0.408), respectively. The rates of adverse events were similar between groups and there were no cases of confirmed pump thrombosis. The incidence of readmissions for low flow alarms was higher in the small BSA group (0.55 vs. 0.24 EPPY). CONCLUSIONS: These findings demonstrate comparable outcomes in patients with small body size and suggest that this parameter should not be an exclusion criterion on patients who are otherwise candidates for HM3 LVAD implantation.
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Superficie Corporal , Corazón Auxiliar , Índice de Masa Corporal , Estudios de Cohortes , Diabetes Mellitus/epidemiología , Diástole , Femenino , Humanos , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiología , Trombosis/epidemiologíaRESUMEN
BACKGROUND: Many patients with American College of Cardiology/American Heart Association Stage D (advanced) heart failure are discharged home on chronic intravenous inotropic support (CIIS) as bridge to surgical therapy or as palliative therapy. This study analyzed the clinical trajectory of patients with advanced heart failure who were on home CIIS. METHODS: We conducted a single-institution, retrospective cohort study of patients on CIIS between 2010 and 2016 (nâ¯=â¯373), stratified by indication for initiation of inotropic support. Study outcomes were time from initiation of CIIS to cessation of therapy, time to death for patients who did not receive surgical therapy and rates of involvement with palliative care. RESULTS: Overall, patients received CIIS therapy for an average of 5.9 months (standard deviation [SD] 7.3). Patients on CIIS as palliative therapy died in an average of 6.2 months (SD 6.6) from the time of initiation of CIIS, and those on CIIS as bridge therapy who did not ultimately receive surgical therapy died after an average of 8.6 months (SD 9.3). Patients who received CIIS as bridge therapy were significantly less likely to receive palliative-care consultation than those on inotropes as palliative therapy, whether or not they underwent surgery. CONCLUSIONS: In this large cohort of patients with advanced HF, patients who on CIIS as palliative therapy survived for 6.2 months, on average, with wide variation among patients. Patients who were on CIIS as bridge therapy but did not ultimately receive surgical therapy received less palliative care despite the high mortality rate in this subgroup.
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Fármacos Cardiovasculares , Insuficiencia Cardíaca , Cardiotónicos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Cuidados Paliativos , Estudios RetrospectivosRESUMEN
Iatrogenic chordal rupture with severe mitral regurgitation is a rare but serious complication associated with the use of Impella device. We present a case of a 47-year-old man with ischemic cardiomyopathy who required insertion of an Impella 5.0 device. During Impella support, he developed acute pulmonary edema secondary to newly diagnosed posterior mitral valve chordal rupture and subsequent severe mitral regurgitation. He underwent implantation of a durable left ventricular assist device with concomitant edge-to-edge mitral valve repair through the apex.
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Rotura Cardíaca , Insuficiencia de la Válvula Mitral , Cuerdas Tendinosas/cirugía , Rotura Cardíaca/etiología , Rotura Cardíaca/cirugía , Humanos , Enfermedad Iatrogénica , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/etiología , Insuficiencia de la Válvula Mitral/cirugíaRESUMEN
Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO2 slope would prognosticate RV dysfunction after LVAD. All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope < 36 (n = 27). We compared the mortality between the 2 groups, as well as the hemodynamic, echocardiographic and clinical markers of RV dysfunction. 570 patients underwent CPET testing. 145 patients were ultimately referred to the advanced heart failure program and 70 patients later received LVAD implantation. Patients with VE/VCO2 slope of ≥ 36 had higher mortality (30.2% vs. 7.4%, p = 0.02) than patients with VE/VCO2 slope < 36 (n = 27). They also had a higher incidence of clinically important RVF (Acute severe 9.3% vs. 0%, Severe 32.6% vs 25.9%, p = 0.03). Patients with a VE/VCO2 slope ≥ 36 had a higher CVP than those with a lower VE/VCO2 slope (11.2 ± 6.1 vs. 6.0 ± 4.8 mmHg, p = 0.007), and were more likely to have a RA/PCWP ≥ 0.63 (65% vs. 19%, p = 0.008) and a PAPI ≤ 2 (57% vs. 13%, p = 0.008). In contrast, peak VO2 < 12 ml/kg/min was not associated with postoperative RV dysfunction or mortality. Elevated preoperative VE/VCO2 slope is a predictor of postoperative mortality, and is associated with postoperative clinical and hemodynamic markers of impaired RV performance.
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Insuficiencia Cardíaca , Corazón Auxiliar , Disfunción Ventricular Derecha , Prueba de Esfuerzo , Insuficiencia Cardíaca/diagnóstico , Humanos , Consumo de Oxígeno , PronósticoRESUMEN
PURPOSE: HER2-targeted therapies are associated with cardiotoxicity which is usually asymptomatic and reversible. We report the updated cardiac safety assessment of patients with compromised heart function receiving HER2-targeted therapy for breast cancer, enrolled in the SAFE-HEaRt trial, at a median follow-up of 3.5 years. METHODS: Thirty patients with stage I-IV HER2-positive breast cancer receiving trastuzumab with or without pertuzumab, or ado-trastuzumab emtansine (T-DM1), with asymptomatic LVEF (left ventricular ejection fraction) 40-49%, were started on cardioprotective medications, with the primary endpoint being completion of HER2-targeted therapy without cardiac events (CE) or protocol-defined asymptomatic worsening of LVEF. IRB-approved follow-up assessment included 23 patients. RESULTS: Median follow-up as of June 2020 is 42 months. The study met its primary endpoint with 27 patients (90%) completing their HER2-targeted therapies without cardiac issues. Of the 23 evaluable patients at long-term f/u, 14 had early stage breast cancer, and 9 had metastatic disease, 8 of whom remained on HER2-targeted therapies. One patient developed symptomatic heart failure with no change in LVEF. There were no cardiac deaths. The mean LVEF improved to 52.1% from 44.9% at study baseline, including patients who remained on HER2-targeted therapy, and those who received prior anthracyclines. CONCLUSIONS: Long-term follow-up of the SAFE-HEaRt study continues to provide safety data of HER2-targeted therapy use in patients with compromised heart function. The late development of cardiac dysfunction is uncommon and continued multi-disciplinary oncologic and cardiac care of patients is vital for improved patient outcomes.
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Neoplasias de la Mama , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Receptor ErbB-2/genética , Volumen Sistólico , Trastuzumab/efectos adversos , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Women differ from men in their left ventricular (LV) structure, function and remodeling with age and diseases. The LV assist device (LVAD) unloads the LV and reversely remodels the heart. We sought to define the effects of sex on longitudinal reverse remodeling after LVAD implantation. METHODS AND RESULTS: Cardiac structure and function were assessed by serial echocardiograms. Mixed effect regression models were constructed to assess the independent contribution of sex to longitudinal changes in cardiac structure and function. A total of 355 consecutive patients with advanced heart failure received continuous flow LVADs between 2006 and 2016. The average age was 56 ± 13 years, 73% were men, and 67% were black. Early (within 3 months) after LVAD implantation, women had a greater reduction in LV dimensions and a greater increase in LV ejection fraction compared with men. These differences were independent of age, body surface area, device type, or ischemic etiology of heart failure. At long-term follow-up, LV dimensions increased slightly over time in women compared with men, but overall, earlier changes were maintained. CONCLUSION: Women had significantly more favorable longitudinal changes in cardiac structure and function in response to LV unloading compared with men. Understanding the cause of sex difference in reverse remodeling after LVAD may help to devise novel therapeutic strategies for women with advanced heart failure.
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Insuficiencia Cardíaca , Corazón Auxiliar , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/terapia , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Función Ventricular Izquierda , Remodelación VentricularRESUMEN
BACKGROUND: LMNA cardiomyopathy presents with electrocardiogram (ECG) abnormalities, conduction system disease (CSD), and/or arrhythmias before the onset of dilated cardiomyopathy (DCM). Knowing the time interval between the onset of CSD and its progression to DCM would help to guide clinical care. METHODS AND RESULTS: We evaluated family members from 16 pedigrees previously identified to carry LMNA mutations for the ages of onset of ECG abnormalities, CSD, or arrhythmia and of left ventricular enlargement (LVE) and/or systolic dysfunction. Of 103 subjects, 64 carried their family LMNA mutation, and 51 (79%) had ECG abnormalities with a mean age of onset of 41.2 years (range 18-76). Ventricular dysfunction was observed in 26 with a mean age of onset of 47.6 years (range 28-82); at diagnosis 9 had systolic dysfunction but no LVE, 5 had LVE but no systolic dysfunction, and 11 had DCM. Of 16 subjects identified with ECG abnormalities who later developed ventricular dysfunction, the median ages of onset by log-rank analyses were 41 and 48 years, respectively. CONCLUSIONS: ECG abnormalities preceded DCM with a median difference of 7 years. Clinical surveillance should occur at least annually in those at risk for LMNA cardiomyopathy with any ECG findings.
Asunto(s)
Cardiomiopatía Dilatada/genética , Electrocardiografía/tendencias , Sistema de Conducción Cardíaco/fisiología , Lamina Tipo A/genética , Disfunción Ventricular/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/epidemiología , Femenino , Estudios de Seguimiento , Sistema de Conducción Cardíaco/patología , Humanos , Lipodistrofia/diagnóstico , Lipodistrofia/epidemiología , Lipodistrofia/genética , Masculino , Persona de Mediana Edad , Factores de Tiempo , Disfunción Ventricular/diagnóstico , Disfunción Ventricular/epidemiología , Adulto JovenRESUMEN
Mutations in TNNT2, encoding cardiac troponin T, commonly shows early onset, aggressive dilated cardiomyopathy (DCM). This observation may influence the decision of whether to undertake clinical genetic testing for TNNT2 in later onset DCM. Further, the trigger for late onset DCM remains enigmatic. A 70-year-old woman, previously healthy with a left ventricular ejection fraction of 50%-55% at age 69, presented with DCM of unknown cause and a 4-month history progressive heart failure requiring cardiac transplantation. Clinical genetic testing revealed a novel TNNT2 R139H mutation but no relevant variants in 18 other DCM genes. Her explanted heart showed partial fatty replacement in the right ventricle. Sequencing for five arrhythmogenic right ventricular dysplasia genes was negative. Functional studies in porcine cardiac skinned fibers reconstituted with the mutant R139H troponin T protein showed decreased Ca(2+) sensitivity at pH 7, characteristic of DCM. Because fatty infiltration may acidify the myocellular environment, maximal force development examined at pH 6.5 was diminished, suggesting a possible environmental trigger. We conclude that the TNNT2 R139H mutation was likely to be disease causing. Further, later age of onset may not be relevant to exclude genetic testing for TNNT2 mutations.
Asunto(s)
Cardiomiopatía Dilatada/genética , Mutación/genética , Miocardio/patología , Troponina T/genética , Edad de Inicio , Anciano , Sustitución de Aminoácidos/genética , Animales , Cardiomiopatía Dilatada/patología , Exones/genética , Femenino , Heterocigoto , Humanos , Intrones/genética , Masculino , Linaje , Sus scrofaRESUMEN
The genetic basis of most of dilated cardiomyopathy (DCM) cases remains unknown. A recent study indicated that mutations in a highly localized five amino acid hotspot in exon 9 of RBM20, a gene encoding a ribonucleic acid-binding protein, caused aggressive DCM. We undertook this study to confi rm and extend the nature of RBM20 mutations in another DCM cohort. Clinical cardiovascular data, family histories, and blood samples were collected from patients with idiopathic DCM. DNA from 312 DCM probands was sequenced for nucleotide alterations in exons 6 through 9 of RBM20, and additional family members as possible. We found six unique RBM20 rare variants in six unrelated probands (1.9%). Four mutations, two of which were novel (R634W and R636C) and two previously identified (R634Q and R636H), were identified in a five amino acid hotspot in exon 6. Two other novel variants (V535I in exon 6 and R716Q in exon 9) were outside of this hotspot. Age of onset and severity of heart failure were variable, as were arrhythmias and conduction system defects, but many subjects suffered severe heart failure resulting in early death or cardiac transplantation. This article concludes that DCM in patients with RBM20 mutations is associated with advanced disease.
Asunto(s)
Cardiomiopatía Dilatada/genética , Mutación Missense/genética , Proteínas de Unión al ARN/genética , Adolescente , Adulto , Anciano , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Proteínas de Unión al ARN/química , Adulto JovenRESUMEN
OBJECTIVES: To determine the effect of a 2-week (six-session) training intervention to improve the ability of disabled older adults to rise from the floor. DESIGN: Prospective intervention trial. SETTING: Congregate housing in Michigan. PARTICIPANTS: Subjects aged 65 and older who admitted to requiring assistance (such as from a person, equipment, or device) in performing at least one of the following mobility-related activities of daily living: transferring, walking, bathing, and toileting. INTERVENTION: Participants were randomly allocated to individual training (n = 17, mean age 81) in strategies to rise from the floor (using for example, certain key intermediate body positions) or a control chair-based flexibility intervention (n = 18, mean age 80). MEASUREMENTS: At baseline and postintervention, residents were queried regarding their rise difficulty (difficulty scale) and symptoms (symptoms scale) associated with the rise and were tested in their ability to perform timed floor-rise tasks. These tasks varied in starting position (supine vs all fours) and in use of a support to assist in rising (no support, use of an end table, use of a chair). RESULTS: Using baseline performance as the covariate, by analysis of covariance (ANCOVA), the training group showed a significant (P <.05) improvement in mean number of rise tasks completed (baseline mean 6.6, postintervention mean 7.3) versus essentially no improvement in the controls. Similarly, by ANCOVA, the training group (compared with controls) showed a significant (P <.05) improvement on the difficulty and symptoms scales. There was no intervention effect for rise time. CONCLUSIONS: A short-term, strategy-based intervention improved floor-rise ability and perceived difficulty and symptoms associated with the rise. This approach, focusing on key intermediate body positions, may be useful in training floor-rise skills, particularly in older adults at risk for falls.