RESUMEN
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.
Asunto(s)
Cardiomiopatía Dilatada , Humanos , Cardiomiopatía Dilatada/diagnóstico , Etnicidad , Familia , Salud de la Familia , Medición de RiesgoRESUMEN
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.
Asunto(s)
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
PURPOSE: The cardiac phenotype of hereditary transthyretin amyloidosis (hTTR) usually presents as a restrictive or hypertrophic cardiomyopathy, and, although rarely observed as dilated cardiomyopathy (DCM), TTR is routinely included in DCM genetic testing panels. However, the prevalence and phenotypes of TTR variants in patients with DCM have not been reported. METHODS: Exome sequences of 729 probands with idiopathic DCM were analyzed for TTR and 35 DCM genes. RESULTS: Rare TTR variants were identified in 2 (0.5%; 95% CI = 0.1%-1.8%) of 404 non-Hispanic White DCM probands; neither of them had features of hTTR. In 1 proband, a TTR His110Asn variant and a variant of uncertain significance in DSP were identified, and in the other proband, a TTR Val50Met variant known to cause hTTR and a likely pathogenic variant in FLNC were identified. The TTR Val142Ile variant was identified in 8 (3.0%) non-Hispanic Black probands, comparable with African/African American Genome Aggregation Database controls (OR = 1.01; 95% CI = 0.46-1.99). CONCLUSION: Among the 729 DCM probands, 2 had rare TTR variants identified without the features of hTTR, and both had other plausible genetic causes of DCM. Moreover, the frequency of TTR Val142Ile was comparable to a control sample. These findings suggest that hTTR variants may have a limited role in patients with DCM without TTR-specific findings.
Asunto(s)
Neuropatías Amiloides Familiares , Cardiomiopatía Dilatada , Neuropatías Amiloides Familiares/genética , Cardiomiopatía Dilatada/genética , Exoma , Pruebas Genéticas , Humanos , Medicina de PrecisiónRESUMEN
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.
Asunto(s)
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
BACKGROUND: Few data support use of 6 over 3 months of antiviral prophylaxis for cytomegalovirus (CMV) disease prevention in donor seropositive/recipient seronegative (D+R-) heart transplant recipients (HTR). METHODS: We retrospectively assessed CMV disease and outcomes in 310 adult HTR between July 5, 2005, and December 30, 2016, at our center. Valganciclovir (VGCV) prophylaxis was given for 3-6 months in the D+R- group. Multivariable models evaluated risk factors for CMV disease in patients who received 3 vs 6 months (±1 month) of prophylaxis, with investigation of inverse probability weighting to correct for confounding variables. RESULTS: The incidence of CMV disease among all patients and the D+R- group was 8.7% (27/310) and 26.5% (22/83), respectively, and included syndrome in 22.2% (6/27) and end-organ involvement in 77.8% (21/27). In a multivariable model, 6 vs 3 months of antiviral prophylaxis was not associated with reduced risk for CMV disease (OR 2.28 [95% CI 0.66, 7.91], P = .19). CMV disease in D+R- HTR was associated with higher rates of hospitalization (87.5% [14/16] vs 6.3% [1/16], P < .001) and for a longer duration than in matched D+R- controls without disease. CONCLUSIONS: Cytomegalovirus disease remains a major cause of morbidity in D+R- HTR. In contrast to documented benefit in D+R- lung and kidney recipients, VGCV duration of 6 months was not associated with a lower incidence of CMV disease in D+R- HTR compared to 3-month duration and should be reconsidered in this patient population.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Trasplante de Corazón , Receptores de Trasplantes , Valganciclovir/uso terapéutico , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Donantes de TejidosRESUMEN
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.
Asunto(s)
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: Patients with heart failure who receive an implantable cardioverter-defibrillator (ICD) for primary prevention (i.e., prevention of a first life-threatening arrhythmic event) may later receive therapeutic shocks from the ICD. Information about long-term prognosis after ICD therapy in such patients is limited. METHODS: Of 829 patients with heart failure who were randomly assigned to ICD therapy, we implanted the ICD in 811. ICD shocks that followed the onset of ventricular tachycardia or ventricular fibrillation were considered to be appropriate. All other ICD shocks were considered to be inappropriate. RESULTS: Over a median follow-up period of 45.5 months, 269 patients (33.2%) received at least one ICD shock, with 128 patients receiving only appropriate shocks, 87 receiving only inappropriate shocks, and 54 receiving both types of shock. In a Cox proportional-hazards model adjusted for baseline prognostic factors, an appropriate ICD shock, as compared with no appropriate shock, was associated with a significant increase in the subsequent risk of death from all causes (hazard ratio, 5.68; 95% confidence interval [CI], 3.97 to 8.12; P<0.001). An inappropriate ICD shock, as compared with no inappropriate shock, was also associated with a significant increase in the risk of death (hazard ratio, 1.98; 95% CI, 1.29 to 3.05; P=0.002). For patients who survived longer than 24 hours after an appropriate ICD shock, the risk of death remained elevated (hazard ratio, 2.99; 95% CI, 2.04 to 4.37; P<0.001). The most common cause of death among patients who received any ICD shock was progressive heart failure. CONCLUSIONS: Among patients with heart failure in whom an ICD is implanted for primary prevention, those who receive shocks for any arrhythmia have a substantially higher risk of death than similar patients who do not receive such shocks.
Asunto(s)
Desfibriladores Implantables/efectos adversos , Insuficiencia Cardíaca/terapia , Anciano , Electrocardiografía , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Riesgo , Taquicardia Ventricular/prevención & control , Fibrilación Ventricular/prevención & controlRESUMEN
BACKGROUND: Although implantable cardioverter-defibrillator (ICD) therapy reduces mortality in moderately symptomatic heart failure patients with an ejection fraction
Asunto(s)
Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/terapia , Prevención Primaria/métodos , Adulto , Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Femenino , Insuficiencia Cardíaca/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos Estadísticos , RiesgoRESUMEN
BACKGROUND: The SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) randomized 2,521 patients with moderate heart failure (HF) to amiodarone, placebo drug, or implantable cardioverter-defibrillator (ICD) therapy. Original trial follow-up ended October 31, 2003. Over a median 45.5-month follow-up, amiodarone, compared with placebo, did not affect survival, whereas randomization to an ICD significantly decreased all-cause mortality by 23%. OBJECTIVES: This study sought to describe the extended treatment group survival of the SCD-HeFT cohort. METHODS: Mortality outcomes for the 1,855 patients alive at the end of the SCD-HeFT trial were collected between 2010 and 2011. These data were combined with the 666 deaths from the original study to compare long-term outcomes overall and for key pre-specified subgroups. RESULTS: Median (25th to 75th percentiles) follow-up was 11.0 (10.0 to 12.2) years. On the basis of intention-to-treat analysis, the ICD group had overall survival benefit versus placebo drug (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.76 to 0.98; p = 0.028). When treatment benefit was examined as a function of time from randomization, attenuation of the ICD benefit was observed after 6 years (p value for the interaction = 0.0015). Subgroup analysis revealed long-term ICD benefit varied according to HF etiology and New York Heart Association (NYHA) functional class: ischemic HF HR: 0.81; 95% CI: 0.69 to 0.95; p = 0.009; nonischemic HF HR: 0.97; 95% CI: 0.79 to 1.20; p = 0.802; NYHA functional class II HR: 0.76; 95% CI: 0.65 to 0.90; p = 0.001; NYHA functional class III HR: 1.06; 95% CI: 0.86 to 1.31; p = 0.575. CONCLUSIONS: Follow-up of SCD-HeFT patients to 11 years demonstrated heterogenous treatment-related patterns of long-term survival with ICD benefit most evident at 11 years for ischemic HF patients and for those with NYHA functional class II symptoms at trial enrollment. (SCD-HeFT 10 Year Follow-up [SCD-HeFT10 Yr]; NCT01058837).
Asunto(s)
Amiodarona , Desfibriladores Implantables/estadística & datos numéricos , Cardioversión Eléctrica , Insuficiencia Cardíaca , Efectos Adversos a Largo Plazo , Anciano , Amiodarona/administración & dosificación , Amiodarona/efectos adversos , Antiarrítmicos/administración & dosificación , Antiarrítmicos/efectos adversos , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Cardioversión Eléctrica/efectos adversos , Cardioversión Eléctrica/métodos , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Humanos , Efectos Adversos a Largo Plazo/diagnóstico , Efectos Adversos a Largo Plazo/etiología , Efectos Adversos a Largo Plazo/mortalidad , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Análisis de SupervivenciaRESUMEN
BACKGROUND: Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure (CHF). Treatment with amiodarone or an implantable cardioverter-defibrillator (ICD) has been proposed to improve the prognosis in such patients. METHODS: We randomly assigned 2521 patients with New York Heart Association (NYHA) class II or III CHF and a left ventricular ejection fraction (LVEF) of 35 percent or less to conventional therapy for CHF plus placebo (847 patients), conventional therapy plus amiodarone (845 patients), or conventional therapy plus a conservatively programmed, shock-only, single-lead ICD (829 patients). Placebo and amiodarone were administered in a double-blind fashion. The primary end point was death from any cause. RESULTS: The median LVEF in patients was 25 percent; 70 percent were in NYHA class II, and 30 percent were in class III CHF. The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent. The median follow-up was 45.5 months. There were 244 deaths (29 percent) in the placebo group, 240 (28 percent) in the amiodarone group, and 182 (22 percent) in the ICD group. As compared with placebo, amiodarone was associated with a similar risk of death (hazard ratio, 1.06; 97.5 percent confidence interval, 0.86 to 1.30; P=0.53) and ICD therapy was associated with a decreased risk of death of 23 percent (0.77; 97.5 percent confidence interval, 0.62 to 0.96; P=0.007) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population. Results did not vary according to either ischemic or nonischemic causes of CHF, but they did vary according to the NYHA class. CONCLUSIONS: In patients with NYHA class II or III CHF and LVEF of 35 percent or less, amiodarone has no favorable effect on survival, whereas single-lead, shock-only ICD therapy reduces overall mortality by 23 percent.
Asunto(s)
Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Insuficiencia Cardíaca/terapia , Anciano , Causas de Muerte , Estudios Cruzados , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Volumen Sistólico , Análisis de SupervivenciaRESUMEN
OBJECTIVES: The authors previously developed the Seattle Proportional Risk Model (SPRM) in systolic heart failure patients without implantable cardioverter-defibrillators (ICDs)to predict the proportion of deaths that were sudden. They subsequently validated the SPRM in 2 observational ICD data sets. The objectives in the present study were to determine whether this validated model could improve identification of clinically important variations in the expected magnitude of ICD survival benefit by using a pivotal randomized trial of primary prevention ICD therapy. BACKGROUND: Recent data show that <50% of nominally eligible subjects receive guideline- recommended primary prevention ICDs. METHODS: In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), a placebo-controlled ICD trial in 2,521 patients with an ejection fraction ≤35% and symptomatic heart failure, we tested the use of patient-level SPRM-predicted probability of sudden death (relative to that of non-sudden death) as a summary measurement of the potential for ICD benefit. A Cox proportional hazards model was used to estimate variations in the relationship between patient-level SPRM predictions and ICD benefit. RESULTS: Relative to use of mortality predictions with the Seattle Heart Failure Model, the SPRM was much better at partitioning treatment benefit from ICD therapy (effect size was 2- to 3.6-fold larger for the ICD×SPRM interaction). ICD benefit varied significantly across SPRM-predicted risk quartiles: for all-cause mortality, a +10% increase with ICD therapy in the first quartile (highest risk of death, lowest proportion of sudden death) to a decrease of 66% in the fourth quartile (lowest risk of death, highest proportion of sudden death; p = 0.0013); for sudden death mortality, a 19% reduction in SPRM quartile 1 to 95% reduction in SPRM quartile 4 (p < 0.0001). CONCLUSIONS: In symptomatic systolic heart failure patients with a Class I recommendation for primary prevention ICD therapy, the SPRM offers a useful patient-centric tool for guiding shared decision making.
Asunto(s)
Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables/estadística & datos numéricos , Insuficiencia Cardíaca , Anciano , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugía , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Pronóstico , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
BACKGROUND: The incidence and clinical and virologic aspects of ganciclovir-resistant cytomegalovirus (CMV) disease have not been well-characterized in heart transplant recipients. METHODS: We retrospectively analyzed all patients who underwent their first heart transplantation during the period from 1 January 1995 through 30 June 2005 at a single health care center. Cox proportional hazard regression was used to assess the relationship between clinical variables and CMV disease. Portions of the UL97 gene were sequenced in patients with slow clinical and/or virologic response to ganciclovir therapy. RESULTS: Cytomegalovirus disease developed in 32 (11.7%) of 274 patients at a median of 4.2 months after transplantation (range, 1.8-11.6 months after transplantation) and was independently associated with donor-seropositive/recipient-seronegative (D+/R-) serostatus (adjusted hazard ratio, 6.93; P<.001). The incidence of ganciclovir-resistant CMV disease was 1.5% overall (4 of 274 patients), 5% among D+/R- serostatus recipients (4 of 80 patients), and 12.5% among patients who developed CMV disease (4 of 32 patients). Ganciclovir-resistant CMV disease was significantly associated with D+/R- serostatus (4 [5%] of 80 vs. 0 [0%] of 153 patients; P=.02), greater prior exposure to ganciclovir (median duration of exposure, 150 vs. 69 days; P=.003), and substantial morbidity, including prolonged CMV-associated hospitalization (median duration of hospitalization, 66 vs. 0 days; P<.01). CONCLUSIONS: CMV disease, including ganciclovir-resistant disease, is an important clinical problem in D+/R- heart transplant recipients who receive antiviral prophylaxis. Strategies specifically designed to reduce the incidence and impact of CMV disease in this population are warranted.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/epidemiología , Ganciclovir/uso terapéutico , Trasplante de Corazón , Citomegalovirus/efectos de los fármacos , Infecciones por Citomegalovirus/prevención & control , Farmacorresistencia Viral , Femenino , Trasplante de Corazón/mortalidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Severe vascular disease is a relative contraindication to heart transplantation (HTx). We addressed the effect of vascular disease on HTx outcomes. METHODS: This is a nonconcurrent cohort study of 402 patients who received HTx at our institution between 1985 and 2004. Pre-transplant vascular evaluation included carotid, lower extremity, and renal artery duplex studies, and CT angiogram when indicated. Patients with severe and nontreatable vascular disease were excluded. Patients were divided into Group 1: those with pre-transplant vasculopathy, and Group 2: those without pre-transplant vasculopathy. Group 1 had 24 patients with 25 vascular lesions: 1 aortic dissection, 2 abdominal aortic aneurysm (AAA)'s, 5 carotid artery stenoses, 1 renal artery stenosis, and 16 peripheral vascular lesions. Interventions were performed to 15 lesions prior to HTx and to 2 lesions after HTx. RESULTS: Median follow-up was 5.5 years. Group 1 had higher incidence of ischemic cardiomyopathy (p<0.001), hypertension (p=0.028), chronic obstructive pulmonary disease (COPD) (p=0.004), and smoking history (p<0.001). There were no differences in sex, hyperlipidemia, diabetes, stroke, or renal dysfunction. Multivariate analysis revealed odds of post-transplant death in Group 1 was 1.4 (95% CI: 0.48-4.1, p=0.54) times greater than that in Group 2. Cox proportional hazards model for survival showed a 50% increase in the hazard of death in patients with pre-transplant vasculopathy, but without statistical significance. Group 1 had higher incidence of post-transplant stroke (p=0.001) but no difference in allograft coronary atherosclerosis. CONCLUSIONS: Pre-transplant vascular disease seems to have negative effect on outcomes after HTx. Larger scale study is needed for further evaluation.
Asunto(s)
Trasplante de Corazón/efectos adversos , Enfermedades Vasculares/complicaciones , Anciano , Enfermedad de la Arteria Coronaria/etiología , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Accidente Cerebrovascular/etiología , Resultado del TratamientoRESUMEN
Postcardiotomy open-chest management has been widely used in cardiac surgery. Although this strategy can be applied to heart transplantation, the use of immunosuppressants in transplant recipients raises particular concerns about sternal wound infection and impaired healing. We performed a retrospective review of 403 patients who had undergone 410 heart transplantations at our institution from 1985 through 2004. Among them, 9 patients (2.2%) had open-chest management postoperatively. There were 8 men and 1 woman, with a mean age of 58 +/- 7 years. The graft ischemic time ranged from 130 to 374 minutes (mean, 218 +/- 99 min), and the cardiopulmonary bypass time ranged from 98 to 360 minutes (mean, 210 +/- 69 min). In all cases, the reason for open-chest management was hemodynamic lability that precluded chest closure after transplantation. One patient also experienced postoperative bleeding. All patients underwent delayed sternal closure between postoperative days 1 and 11 (median, 4 days). Delayed sternal closure did not cause any significant hemodynamic changes. One patient died of stroke on postoperative day 22. No patient had sternal wound infection or impaired wound healing during the follow-up period. We conclude that, when required, open-chest management is an effective and safe measure for hemodynamically unstable heart transplant patients.
Asunto(s)
Trasplante de Corazón/métodos , Esternón/cirugía , Adulto , Femenino , Trasplante de Corazón/fisiología , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Estudios Retrospectivos , Cicatrización de HeridasRESUMEN
BACKGROUND: Heart transplant remains the definitive therapy for advanced heart failure patients but is limited by organ availability. We identified a large number of donor hearts from our organ procurement organization (OPO) being exported to other regions. METHODS: We engaged a multidisciplinary team including transplant surgeons, cardiologists, and our OPO colleagues to identify opportunities to improve our center-specific organ utilization rate. We performed a retrospective analysis of donor offers before and after institution of a novel review process. RESULTS: Each donor offer made to our program was reviewed on a monthly basis from July 2013 to June 2014 and compared with the previous year. This review process resulted in a transplant utilization rate of 28% for period 1 versus 49% for period 2 (P = .007). Limiting the analysis to offers from our local OPO changed our utilization rate from 46% to 75% (P = .02). Transplant volume increased from 22 to 35 between the 2 study periods. Thirty-day and 1-year mortality were unchanged over the 2 periods. A total of 58 hearts were refused by our center and transplanted at other centers. During period 1, the 30-day and 1-year survival rates for recipients of those organs were 98% and 90%, respectively, comparable with our historical survival data. CONCLUSIONS: The simple process of systematically reviewing donor turndown events as a group tended to reduce variability, increase confidence in expanded criteria for donors, and resulted in improved donor organ utilization and transplant volumes.
Asunto(s)
Selección de Donante/métodos , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/métodos , Donantes de Tejidos/provisión & distribución , Adulto , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Trasplante de Corazón/mortalidad , Humanos , Masculino , Grupo de Atención al Paciente , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , WashingtónRESUMEN
The usefulness of low relative lymphocyte count as an independent predictor of death/urgent transplant in patients with heart failure (HF) and the association between low relative lymphocyte count and neurohormone and cytokine activation were investigated. Relative lymphocyte count, clinical variables, neurohormones, and cytokines were measured in 129 outpatients with HF. Follow-up extended to a mean of 3.0 +/- 1.2 years for death/urgent transplant. Low relative lymphocyte count was independently associated with a 3.4-fold increased risk of death/urgent transplant. Relative lymphocyte count was positively associated with hemoglobin and inversely associated with age, jugular venous pressure, creatinine, leukocyte count, and soluble tumor necrosis factor receptor-1. There was only a borderline inverse association with cortisol levels during evening hours.
Asunto(s)
Muerte Súbita Cardíaca , Insuficiencia Cardíaca/sangre , Trasplante de Corazón , Recuento de Linfocitos , Biomarcadores/sangre , Citocinas/sangre , Muerte Súbita Cardíaca/epidemiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/mortalidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Norepinefrina/sangre , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Radioinmunoensayo , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Although small, randomized trials have shown that statin use is associated with decreased risks of mortality and severe rejection, no study has examined statin therapy as used in actual practice in large numbers of heart transplant recipients. We analyzed data from the Heart Transplant Lipid Registry (n = 12 centers). Patients were included if they underwent transplantation between 1995 and 1999, survived >/=30 days after transplantation, and had >/=30 days of Registry follow-up. Multivariable Cox regression models, with propensity scoring performed to adjust for nonrandom allocation of statin therapy, were performed to determine the association of statin therapy with death and fatal rejection. The study included 1,186 patients, with a mean follow-up of 580 +/- 469 days; 937 patients (79%) received statin therapy. Overall, 71 patients (6%) died and 40 (3.4%) had fatal rejection. The statin group had a lower frequency of death (4% vs 13.7%, p <0.0001) and fatal rejection (2.4% vs 7.2%, p = 0.0001). Using multivariable Cox regression, with propensity scoring included to adjust for likelihood of receiving statin therapy, statin use was the only factor associated with lower risk of death (hazard ratio 0.29, 95% confidence interval 0.13 to 0.67) and fatal rejection (hazard ratio 0.27, 95% confidence interval 0.09 to 0.78). This study represents the largest population of heart transplant recipients analyzed for the relation between statin therapy and clinical outcomes in actual practice. Statin therapy was significantly associated with lower risk of death and fatal rejection, benefits that were independent of lipid values.
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Rechazo de Injerto/mortalidad , Trasplante de Corazón , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipidemias/tratamiento farmacológico , Distribución de Chi-Cuadrado , Femenino , Trasplante de Corazón/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
A 55-year-old woman with a history of complete heart block, atrial flutter, and progressive right ventricular failure was referred to our tertiary care center to be evaluated for cardiac transplantation. The patient's clinical course included worsening right ventricular dysfunction for 3 years before the current evaluation. Our clinical findings raised concerns about arrhythmogenic right ventricular cardiomyopathy. Noninvasive imaging, including a positron emission tomographic scan, did not reveal obvious myocardial pathologic conditions. Given the end-stage nature of the patient's right ventricular failure and her dependence on inotropic agents, she underwent urgent listing and subsequent heart transplantation. Pathologic examination of the explanted heart revealed isolated right ventricular sarcoidosis with replacement fibrosis. Biopsy samples of the cardiac allograft 6 months after transplantation showed no recurrence of sarcoidosis. This atypical presentation of isolated cardiac sarcoidosis posed a considerable diagnostic challenge. In addition to discussing the patient's case, we review the relevant medical literature and discuss the need for updated differential diagnostic criteria for end-stage right ventricular failure that mimics arrhythmogenic right ventricular cardiomyopathy.
Asunto(s)
Displasia Ventricular Derecha Arritmogénica/diagnóstico , Cardiomiopatías , Trasplante de Corazón/métodos , Ventrículos Cardíacos/patología , Sarcoidosis , Disfunción Ventricular Derecha , Aleteo Atrial/etiología , Bloqueo Atrioventricular/etiología , Cardiomiopatías/complicaciones , Cardiomiopatías/diagnóstico , Cardiomiopatías/fisiopatología , Cardiomiopatías/cirugía , Cardiotónicos/uso terapéutico , Diagnóstico Diferencial , Progresión de la Enfermedad , Ecocardiografía/métodos , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Sarcoidosis/fisiopatología , Sarcoidosis/cirugía , Resultado del Tratamiento , Disfunción Ventricular Derecha/diagnóstico , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/cirugíaRESUMEN
OBJECTIVES: The purpose of this study was to determine if 6-min walk test data assists in treatment decisions for patients with heart failure. BACKGROUND: In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), a pre-specified subgroup analysis showed that patients with New York Heart Association functional class III symptoms did not benefit from implantable cardioverter-defibrillator (ICD) therapy and appeared to be harmed by amiodarone, whereas New York Heart Association functional class II patients obtained significant survival benefit from ICD. We postulated that a more objective measure of functional capacity, such as 6-min walk (6MW) distance, might provide a better tool for selecting these preventive therapies. METHODS: A 6MW test was performed before randomization in 2,397 patients. Median follow-up was 45.5 months. All-cause mortality was the primary endpoint, with cause-specific mortality (heart failure, arrhythmic) examined in secondary analyses. RESULTS: The hazard ratios (HRs) for ICD therapy compared to placebo were estimated within tertiles of baseline 6MW distance: HR: 0.42 (95% confidence interval [CI]: 0.26 to 0.66) for 6MW distance >386 m (top tertile); HR: 0.57 (95% CI: 0.39 to 0.83) for 6MW distance 288 to 386 m (middle tertile); and HR: 1.02 (95% CI: 0.75 to 1.39) for 6MW distance <288 m (bottom tertile). The corresponding HRs for amiodarone compared to placebo were 0.68 (95% CI: 0.46 to 1.02) for the top, 0.86 (95% CI: 0.61 to 1.21) for the middle, and 1.56 (95% CI: 1.17 to 2.09) for the bottom tertile. The 6MW distance was inversely related to heart failure-related mortality but not to arrhythmic mortality. ICD therapy reduced arrhythmic mortality in the top 2 tertiles of 6MW, but had no effect on heart failure mortality. CONCLUSIONS: A baseline 6MW distance <288 m identified a subgroup of SCD-HeFT patients who were harmed by amiodarone therapy and did not benefit from ICD. (Sudden Cardiac Death in Heart Failure Trial [SCD-HeFT]; NCT00000609).