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BACKGROUND: Extensive evidence from single-center studies indicates that a subset of patients with chronic advanced heart failure (HF) undergoing left ventricular assist device (LVAD) support show significantly improved heart function and reverse structural remodeling (ie, termed "responders"). Furthermore, we recently published a multicenter prospective study, RESTAGE-HF (Remission from Stage D Heart Failure), demonstrating that LVAD support combined with standard HF medications induced remarkable cardiac structural and functional improvement, leading to high rates of LVAD weaning and excellent long-term outcomes. This intriguing phenomenon provides great translational and clinical promise, although the underlying molecular mechanisms driving this recovery are largely unknown. METHODS: To identify changes in signaling pathways operative in the normal and failing human heart and to molecularly characterize patients who respond favorably to LVAD unloading, we performed global RNA sequencing and phosphopeptide profiling of left ventricular tissue from 93 patients with HF undergoing LVAD implantation (25 responders and 68 nonresponders) and 12 nonfailing donor hearts. Patients were prospectively monitored through echocardiography to characterize their myocardial structure and function and identify responders and nonresponders. RESULTS: These analyses identified 1341 transcripts and 288 phosphopeptides that are differentially regulated in cardiac tissue from nonfailing control samples and patients with HF. In addition, these unbiased molecular profiles identified a unique signature of 29 transcripts and 93 phosphopeptides in patients with HF that distinguished responders after LVAD unloading. Further analyses of these macromolecules highlighted differential regulation in 2 key pathways: cell cycle regulation and extracellular matrix/focal adhesions. CONCLUSIONS: This is the first study to characterize changes in the nonfailing and failing human heart by integrating multiple -omics platforms to identify molecular indices defining patients capable of myocardial recovery. These findings may guide patient selection for advanced HF therapies and identify new HF therapeutic targets.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Humanos , Transcriptoma , Estudos Prospectivos , Fosfopeptídeos/metabolismo , Proteômica , Doadores de Tecidos , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismoRESUMO
BACKGROUND: Assessment of volume status through the estimation of central venous pressure (CVP) is integral in the care of heart failure (HF). Bedside assessment is limited by obesity, variation in physical examination skills, and expertise in ultrasonography. OBJECTIVE: To validate the accuracy of quantitative and qualitative point-of-care ultrasonography assessment of jugular venous pressure (JVP) in predicting elevated CVP. DESIGN: Prospective observational study using convenience sampling. SETTING: 2 U.S. academic hospitals. PATIENTS: Adult patients undergoing right heart catheterization between 5 February 2019 and 1 March 2021. MEASUREMENTS: Estimation of the JVP height by handheld ultrasound device (uJVP), JVP by traditional physical examination, and qualitative presence of a distended uJVP in the upright position (upright-uJVP) was done before invasive measurements. Receiver-operating characteristic analysis of the uJVP was compared with invasive hemodynamics. RESULTS: In 100 participants undergoing right heart catheterization for HF indications (mean age, 59.6 years; 44% with preserved ejection fraction), the uJVP in a reclined position accurately predicted elevated right atrial pressure (RAP) (>10 mm Hg), with an area under the curve of 0.84. A positive uJVP in the upright position was 94.6% specific for predicting elevated RAP. LIMITATION: Limited examiners, only 2 centers, and convenience sampling. CONCLUSION: Point-of-care ultrasonography assessment of the uJVP is feasible, reproducible, and accurately predictive of elevated CVPs in patients undergoing right heart catheterization. Further investigation of clinical application of ultrasound-measured JVP seems warranted. PRIMARY FUNDING SOURCE: None.
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Insuficiência Cardíaca , Hiperemia , Adulto , Pressão Venosa Central , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Veias Jugulares/diagnóstico por imagem , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito , UltrassonografiaRESUMO
Since the advent of coronary angiography, the standard for reporting of coronary lesion severity has been to utilize percent diameter stenosis (%DS). Given the imperfections of %DS as well as the widespread availability of intraprocedural intracoronary imaging and physiology assessment, it is time to consider a simpler yet more clinically relevant lesion assessment system. We compiled ten actual cases and presented these cases to 10 operators, providing 100 independent lesion assessments. For each case, operators were asked to describe lesions using %DS and a simplified lesion assessment system. We assessed the relationship between %DS and qualitative lesion assessment as well as the relationship of both measurements to the chosen plan. Greater variability exists with %DS than with qualitative lesion assessment. Despite this, there is good correlation between %DS and the qualitative lesion assessment (ρ = 0.8221). There remains overlap of lesion assessment using the qualitative lesion assessment tool suggesting that even with this simpler tool, there remains interobserver variability (ICC = 0.5164, 95% confidence interval [CI] 0.2924-0.7955). When assessing how both lesion assessment, there appears to be a stronger correlation between the qualitative lesion assessment and the chosen plan versus the %DS and the chosen plan (ρ = 0.9069 vs ρ = 0.8001, P < .01). Given the superior performance of the proposed qualitative system and the ability to estimate lesion severity using both anatomic and clinical factors, we feel that professional societies and clinicians should begin to embrace this simplified means of lesion assessment.
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Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Humanos , Variações Dependentes do Observador , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: To identify predictors of 30-day all-cause mortality for patients with cardiogenic shock secondary to acute coronary syndrome (ACS-CS) who require short-term mechanical circulatory support (ST-MCS). BACKGROUND: ACS-CS mortality is high. ST-MCS is an attractive treatment option for hemodynamic support and stabilization of deteriorating patients. Mortality prediction modeling for ACS-CS patients requiring ST-MCS has not been well-defined. METHODS: The Utah Cardiac Recovery (UCAR) Shock database was used to identify patients admitted with ACS-CS requiring ST-MCS devices between May 2008 and August 2018. Pre-ST-MCS clinical, laboratory, echocardiographic, and angiographic data were collected. The primary endpoint was 30-day all-cause mortality. A weighted score comprising of pre-ST-MCS variables independently associated with 30-day all-cause mortality was derived and internally validated. RESULTS: A total of 159 patients (mean age, 61 years; 78% male) were included. Thirty-day all-cause mortality was 49%. Multivariable analysis resulted in four independent predictors of 30-day all-cause mortality: age, lactate, SCAI CS classification, and acute kidney injury. The model had good calibration and discrimination (area under the receiver operating characteristics curve 0.80). A predictive score (ranging 0-4) comprised of age ≥ 60 years, pre-ST-MCS lactate ≥2.5 mmol/L, AKI at time of ST-MCS implementation, and SCAI CS stage E effectively risk stratified our patient population. CONCLUSION: The ACS-MCS score is a simple and practical predictive score to risk-stratify CS secondary to ACS patients based on their mortality risk. Effective mortality risk assessment for ACS-CS patients could have implications on patient selection for available therapeutic strategy options.
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Coração Auxiliar , Choque Cardiogênico , Feminino , Hemodinâmica , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Studies have indicated differences between Asians and Whites in their propensity for stroke, coronary artery disease, heart failure, bleeding and thrombosis. We investigated whether Asian-Americans on durable left ventricular assist devices (LVADs) exhibit differential morbidity and mortality when compared to Whites. METHODS: We analysed prospectively collected data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database to compare the outcomes after LVAD implantation of Asians versus Whites. RESULTS: In total, 7,018 patients were included, 130 were identified as Asian-Americans. Asian-Americans were younger, had lower body mass index, higher serum bilirubin and lower albumin levels. In a multivariable regression model, there was no difference in survival between the two groups. Asian-Americans had lower incidence of device malfunction and after adjusting for multiple factors this remained lower. The adjusted risk of a major safety composite outcome, including major bleeding, major infection, stroke and device malfunction, revealed no difference between the two groups. CONCLUSIONS: Although prior studies have reported worse cardiac surgery outcomes in Asians, in this INTERMACS analysis Asian-Americans appear to have similar survival and risk of adverse events as their White counterparts. The incidence of device malfunction was lower in the Asian-Americans, both in a univariate model and after adjusting for multiple clinical factors. Future, larger studies of Asian-Americans with end-stage heart failure and LVAD support are warranted to confirm these results.
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Asiático , Insuficiência Cardíaca/terapia , Ventrículos do Coração/fisiopatologia , Coração Auxiliar , Sistema de Registros , Adulto , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemAssuntos
Serviços Médicos de Emergência/métodos , Coração Auxiliar , Equipe de Respostas Rápidas de Hospitais , Estudo de Prova de Conceito , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Choque Cardiogênico/mortalidadeRESUMO
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common, complex syndrome associated with elevated morbidity and mortality. Patients with HFpEF have a high prevalence of comorbidities, including hypertension, diabetes mellitus, and obesity, which are closely related to the underlying mechanisms of the disease. Lifestyle modification with weight loss and physical activity can improve risk factors and functional outcomes in HFpEF. We sought to observe daily physical activity and determine whether utilizing an activity tracker can enhance functional status in HFpEF patients. METHODS: We performed a prospective analysis of 57 patients with HFpEF from 2021 to 2023 at a single academic medical center who utilized a Fitbit to record one year of daily step activity. The patients were evaluated in the ambulatory setting for an initial visit and subsequently at intervals of 3, 6, and 12 months to gather vitals, labs, physical exam, and functional measurements, including the Six-Minute Walk Test (6MWT) and Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12). Associations between variables were assessed using Pearson's r correlation using Stata 18.0. RESULTS: Of the 49 patients who completed the study, the mean age was 68.1 ± 10.2 years, with 67% of patients identifying as female. The average BMI was 36.4 ± 8.6 kg/m2. Across each time interval, the median numbers of steps per day were 4,113 (2,517-6,520) (1-3 months), 4,583 (2,532-6,326) (4-6 months), and 3,957 (2,942-5,982) (7-12 months). There was no statistically significant variation in daily step count (p=0.06). We observed a statistically significant increase of 66 (6-200) feet in the 6MWT (p= 0.002) from baseline (1,175 (910-1,400)) to 12 months (1,321 (1,000-1,550)). The daily step count was highly correlated with the 6MWT across all time points (1-3 months: r= .70, p< .001; 4-6 months: r= .61, p< .001; 7-12 months: r= .69, p< .001). The total KCCQ-12 scores increased by 6.8 (-4.2-19.8) points (p=0.005) from baseline (60.1 (41.7-73.4)) to 12 months (69.8 (50-84.4)). Among the sub-categories of the questionnaire, we observed a positive correlation between physical limitation scores and daily step count (1-3 months: r= .47, p=.001; 4-6 months: r= .63, p< .001; 7-12 months: r= .56, p= .001). Of interest, one patient who was taking over 15,000 daily steps scored their physical limitation 10-20 points lower than those taking less than half the steps and had one of the lowest quality of life scores in the cohort, reflecting the subjective nature of heart failure (HF) symptoms. CONCLUSION: Fitbit technology offers a convenient means to monitor real-time physical activity in patients with HFpEF. Utilizing a Fitbit to record daily step activity enhances health-related quality of life in this population. In contrast to the improved average total KCCQ-12 score, we did not observe a clinically significant increase in the 6MWT over the course of the year. Our findings establish the utility of daily step count as a valuable surrogate for six-minute walk distance.
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Background: D2 aortic stenosis (AS) is the highest risk AS subtype with worse operative and mortality outcomes. This study aimed to investigate the quality of life (QoL) and left ventricular ejection fraction (LVEF) in patients with classic (D2 subtype) low-flow/low-gradient AS who underwent transcatheter aortic valve replacement (TAVR). Methods: In total, 634 patients with severe AS underwent TAVR at our institution from 2014 to 2020, of whom 76 met criteria for classic D2 AS with reduced LVEF. Echocardiographic and clinical outcomes including mortality, stroke, pacemaker placement (PPM), and readmission at baseline were compared with those at 30 days and 1 year. QoL data were extracted from the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Results: The average baseline Society of Thoracic Surgeons risk score for patients with D2 AS was 7.66 ± 6.76. Patients with D2 AS reported improved QoL post-TAVR. The average baseline KCCQ-12 score was 39.5 ± 20, with improvement to 68.9 ± 20.6 at 30 days (P < .01) and 74.9 ± 17.5 at 1 year (P < .01). Mortality was 0% at 30 days and 18.4% at 1 year. The average baseline LVEF was 36.1 ± 9.4. Left ventricular function improved to 43.5 ± 12.9 (P <.001) at 30 days and 46.3 ± 11.2 (P = .03) at 1 year. Complications post-TAVR at 30 days included stroke (1.3%) and PPM (11.8%). Patients with D2 AS exhibited higher baseline conduction defects including atrial fibrillation and higher postoperative PPM than those with other subtypes. Conclusions: Patients with D2 AS had significantly improved LVEF and QoL following TAVR at 30 days and 1 year. Postoperative rates of new PPM were higher than other subtypes, while stroke, dialysis, and mortality were lower than expected, supporting the benefit of TAVR in this high-risk group.
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BACKGROUND: Type 2 diabetes is prevalent in cardiovascular disease and contributes to excess morbidity and mortality. We sought to investigate the effect of glycemia on functional cardiac improvement, morbidity, and mortality in durable left ventricular assist device (LVAD) recipients. METHODS AND RESULTS: Consecutive patients with an LVAD were prospectively evaluated (n=531). After excluding patients missing pre-LVAD glycated hemoglobin (HbA1c) measurements or having inadequate post-LVAD follow-up, 375 patients were studied. To assess functional cardiac improvement, we used absolute left ventricular ejection fraction change (ΔLVEF: LVEF post-LVAD-LVEF pre-LVAD). We quantified the association of pre-LVAD HbA1c with ΔLVEF as the primary outcome, and all-cause mortality and LVAD-related adverse event rates (ischemic stroke/transient ischemic attack, intracerebral hemorrhage, gastrointestinal bleeding, LVAD-related infection, device thrombosis) as secondary outcomes. Last, we assessed HbA1c differences pre- and post-LVAD. Patients with type 2 diabetes were older, more likely men suffering ischemic cardiomyopathy, and had longer heart failure duration. Pre-LVAD HbA1c was inversely associated with ΔLVEF in patients with nonischemic cardiomyopathy but not in those with ischemic cardiomyopathy, after adjusting for age, sex, heart failure duration, and left ventricular end-diastolic diameter. Pre-LVAD HbA1c was not associated with all-cause mortality, but higher pre-LVAD HbA1c was shown to increase the risk of intracerebral hemorrhage, LVAD-related infection, and device thrombosis by 3 years on LVAD support (P<0.05 for all). HbA1c decreased from 6.68±1.52% pre-LVAD to 6.11±1.33% post-LVAD (P<0.001). CONCLUSIONS: Type 2 diabetes and pre-LVAD glycemia modify the potential for functional cardiac improvement and the risk for adverse events on LVAD support. The degree and duration of pre-LVAD glycemic control optimization to favorably affect these outcomes warrants further investigation.
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Glicemia , Diabetes Mellitus Tipo 2 , Hemoglobinas Glicadas , Insuficiência Cardíaca , Coração Auxiliar , Função Ventricular Esquerda , Humanos , Masculino , Coração Auxiliar/efeitos adversos , Feminino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas/metabolismo , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/fisiopatologia , Idoso , Glicemia/metabolismo , Estudos Prospectivos , Volume Sistólico , Resultado do Tratamento , Recuperação de Função Fisiológica , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Cardiogenic shock (CS) mortality remains near 40%. In addition to inadequate cardiac output, patients with severe CS may exhibit vasodilation. We aimed to examine the prevalence and consequences of vasodilation in CS. METHODS: We analyzed all patients hospitalized at a CS referral center who were diagnosed with CS stages B to E and did not have concurrent sepsis or recent cardiac surgery. Vasodilation was defined by lower systemic vascular resistance (SVR), higher norepinephrine equivalent dose, or a blunted SVR response to pressors. Threshold SVR values were determined by their relation to 14-day mortality in spline models. The primary outcome was death within 14 days of CS onset in multivariable-adjusted Cox models. RESULTS: This study included 713 patients with a mean age of 60 years and 27% females; 14-day mortality was 28%, and 38% were vasodilated. The median SVR was 1308 dynesâ¢sâ¢cm-5 (interquartile range, 870-1652), median norepinephrine equivalent was 0.11 µg/kg per minute (interquartile range, 0-0.2), and 28% had a blunted pressor response. Each 100-dynesâ¢sâ¢cm-5 decrease in SVR below 800 was associated with 20% higher mortality (adjusted hazard ratio, 1.23; P=0.004). Each 0.1-µg/kg per minute increase in norepinephrine equivalent dose was associated with 15% higher mortality (adjusted hazard ratio, 1.12; P<0.001). A blunted pressor response was associated with a nearly 2-fold mortality increase (adjusted hazard ratio, 1.74; P=0.003). CONCLUSIONS: Pathophysiologic vasodilation is prevalent in CS and independently associated with an increased risk of death. CS vasodilation can be identified by SVR <800 dynesâ¢sâ¢cm-5, high doses of pressors, or a blunted SVR response to pressors. Additional studies exploring mechanisms and treatments for CS vasodilation are needed.
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Importance: The existing models predicting right ventricular failure (RVF) after durable left ventricular assist device (LVAD) support might be limited, partly due to lack of external validation, marginal predictive power, and absence of intraoperative characteristics. Objective: To derive and validate a risk model to predict RVF after LVAD implantation. Design, Setting, and Participants: This was a hybrid prospective-retrospective multicenter cohort study conducted from April 2008 to July 2019 of patients with advanced heart failure (HF) requiring continuous-flow LVAD. The derivation cohort included patients enrolled at 5 institutions. The external validation cohort included patients enrolled at a sixth institution within the same period. Study data were analyzed October 2022 to August 2023. Exposures: Study participants underwent chronic continuous-flow LVAD support. Main Outcome and Measures: The primary outcome was RVF incidence, defined as the need for RV assist device or intravenous inotropes for greater than 14 days. Bootstrap imputation and adaptive least absolute shrinkage and selection operator variable selection techniques were used to derive a predictive model. An RVF risk calculator (STOP-RVF) was then developed and subsequently externally validated, which can provide personalized quantification of the risk for LVAD candidates. Its predictive accuracy was compared with previously published RVF scores. Results: The derivation cohort included 798 patients (mean [SE] age, 56.1 [13.2] years; 668 male [83.7%]). The external validation cohort included 327 patients. RVF developed in 193 of 798 patients (24.2%) in the derivation cohort and 107 of 327 patients (32.7%) in the validation cohort. Preimplant variables associated with postoperative RVF included nonischemic cardiomyopathy, intra-aortic balloon pump, microaxial percutaneous left ventricular assist device/venoarterial extracorporeal membrane oxygenation, LVAD configuration, Interagency Registry for Mechanically Assisted Circulatory Support profiles 1 to 2, right atrial/pulmonary capillary wedge pressure ratio, use of angiotensin-converting enzyme inhibitors, platelet count, and serum sodium, albumin, and creatinine levels. Inclusion of intraoperative characteristics did not improve model performance. The calculator achieved a C statistic of 0.75 (95% CI, 0.71-0.79) in the derivation cohort and 0.73 (95% CI, 0.67-0.80) in the validation cohort. Cumulative survival was higher in patients composing the low-risk group (estimated <20% RVF risk) compared with those in the higher-risk groups. The STOP-RVF risk calculator exhibited a significantly better performance than commonly used risk scores proposed by Kormos et al (C statistic, 0.58; 95% CI, 0.53-0.63) and Drakos et al (C statistic, 0.62; 95% CI, 0.57-0.67). Conclusions and Relevance: Implementing routine clinical data, this multicenter cohort study derived and validated the STOP-RVF calculator as a personalized risk assessment tool for the prediction of RVF and RVF-associated all-cause mortality.
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Sistema Cardiovascular , Insuficiência Cardíaca , Coração Auxiliar , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Coração Auxiliar/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Feminino , Adulto , IdosoRESUMO
BACKGROUND: Transvenous pacemaker and defibrillator lead extraction is a higher risk procedure with variation in preferred technique. A frequently fatal complication of this procedure is perforation of the superior vena cava. We have developed a tandem femoral-superior technique that incorporates snaring of targeted leads from a femoral approach combined with use of a rotational cutting sheath advanced over the lead from the subclavian vein. OBJECTIVE: We sought to evaluate the safety and efficacy of a tandem femoral-superior approach to lead extraction. METHODS: Consecutive patients undergoing transvenous extraction of at least 1 pacemaker or defibrillator lead with implant duration ≥1 year in which a tandem femoral-superior technique was used as the initial extraction strategy were included. The registry spanned 2010-2018 and consisted of procedures performed by a single primary operator. RESULTS: A total of 131 patients were included. A total of 267 leads with a mean implant duration of 9.8 years, including 90 defibrillator leads (33.7%), were targeted for extraction. No superior vena cava perforation or other vascular damage occurred. Clinical procedural success was achieved in 96.2% of cases. There were 5 major complications (3.8% of patients), with 3 being pericardial effusion requiring intervention. There were no deaths. CONCLUSION: A tandem femoral-superior approach to lead extraction effectively eliminated superior vena cava injury. This is a safe and effective technique for transvenous lead extraction.
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Desfibriladores Implantáveis , Marca-Passo Artificial , Traumatismos Torácicos , Desfibriladores Implantáveis/efeitos adversos , Remoção de Dispositivo/métodos , Humanos , Marca-Passo Artificial/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Veia Cava Superior/lesões , Veia Cava Superior/cirurgiaRESUMO
Objective: In chronic heart failure (HF) patients supported with continuous-flow left ventricular assist device (CF-LVAD), we aimed to assess the clinical association of pre-LVAD QRS duration (QRSd) with post-LVAD cardiac recovery, and its correlation with pre- to post-LVAD change in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD). Methods: Chronic HF patients (n = 402) undergoing CF-LVAD implantation were prospectively enrolled, at one of the centers comprising the U.T.A.H. (Utah Transplant Affiliated Hospitals) consortium. After excluding patients with acute HF etiologies, hypertrophic or infiltrative cardiomyopathy, and/or inadequate post-LVAD follow up (<3 months), 315 patients were included in the study. Cardiac recovery was defined as LVEF ≥ 40 % and LVEDD < 6 cm within 12 months post-LVAD implantation. Patients fulfilling this condition were termed as responders (R) and results were compared with non-responders (NR). Results: Thirty-five patients (11 %) achieved 'R' criteria, and exhibited a 15 % shorter QRSd compared to 'NR' (123 ± 37 ms vs 145 ± 36 ms; p < 0.001). A univariate analysis identified association of baseline QRSd with post-LVAD cardiac recovery (OR: 0.986, 95 % CI: 0.976-0.996, p < 0.001). In a multivariate logistic regression model, after adjusting for duration of HF (OR: 0.990, 95 % CI: 0.983-0.997, p = 0.006) and gender (OR: 0.388, 95 % CI: 0.160-0.943, p = 0.037), pre-LVAD QRSd exhibited a significant association with post-LVAD cardiac structural and functional improvement (OR: 0.987, 95 % CI: 0.977-0.998, p = 0.027) and the predictive model showed a c-statistic of 0.73 with p < 0.001. The correlations for baseline QRSd with pre- to post-LVAD change in LVEF and LVEDD were also investigated in 'R' and 'NR' groups. Conclusion: Chronic advanced HF patients with a shorter baseline QRSd exhibit an increased potential for cardiac recovery after LVAD support.
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Background Recent prospective multicenter data from patients with advanced heart failure demonstrated that left ventricular assist device (LVAD) support combined with standard heart failure medications, induced significant cardiac structural and functional improvement, leading to high rates of LVAD weaning in selected patients. We investigated whether preintervention myocardial and systemic inflammatory burden could help identify the subset of patients with advanced heart failure prone to LVAD-mediated cardiac improvement to guide patient selection, treatment, and monitoring. Methods and Results Ninety-three patients requiring durable LVAD were prospectively enrolled. Myocardial tissue and blood were acquired during LVAD implantation, for measurement of inflammatory markers. Cardiac structural and functional improvement was prospectively assessed via serial echocardiography. Eleven percent of the patients showed significant reverse remodeling following LVAD support (ie, responders). Circulating tumor necrosis factor alpha, interleukin (IL)-4, IL-5, IL-6, IL-7, IL-13, and interferon gamma were lower in responders, compared with nonresponders (P<0.05, all comparisons). The myocardial tissue signal transducer and activator of transcription-3, an inflammatory response regulator, was less activated in responders (P=0.037). Guided by our tissue studies and a multivariable dichotomous regression analysis, we identified that low levels of circulating interferon gamma (odds ratio [OR], 0.06; 95% CI, 0.01-0.35) and tumor necrosis factor alpha (OR, 0.05; 95% CI, 0.00-0.43), independently predict cardiac improvement, creating a 2-cytokine model effectively predicting responders (area under the curve, 0.903; P<0.0001). Conclusions Baseline myocardial and systemic inflammatory burden inversely correlates with cardiac improvement following LVAD support. A circulating 2-cytokine model predicting significant reverse remodeling was identified, warranting further investigation as a practical preintervention tool in identifying patients prone to LVAD-mediated cardiac improvement and device weaning.
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Citocinas , Insuficiência Cardíaca , Coração Auxiliar , Biomarcadores/análise , Citocinas/análise , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Interferon gama , Prognóstico , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Cardiac allograft vasculopathy (CAV) remains an important source of mortality after heart transplant. The aim of our study was to identify structural and microvasculature changes in severe CAV. METHODS AND RESULTS: The study group included heart transplant recipients with severe CAV who underwent retransplantation (severe CAV, n=20). Control groups included time from transplant matched cardiac transplant recipients without CAV (transplant control, n=20), severe ischemic cardiomyopathy patients requiring left ventricular assist device implantation (ischemic control, n=18), and normal hearts donated for research (donor control, n=10). We collected baseline demographic information, echocardiography data, and performed histopathologic examination of myocardial microvasculature. Echocardiographic features of severe CAV included lack of eccentric remodeling and presence of significant diastolic dysfunction. In contrast, diastolic function was preserved in transplant control subjects. Histopathologic examination showed increased interstitial fibrosis among severe CAV, transplant controls, and ischemic control patients. Compared with transplant controls, severe CAV subjects had reduced capillary density and increased capillary wall thickness ( P<0.05). CONCLUSIONS: Our results suggest that the marked diastolic dysfunction and resultant symptoms in patients with severe CAV may be secondary to the loss of microvasculature and remodeling of remaining microvessels rather than a consequence of interstitial fibrosis. The clinical significance and potential therapeutic implications of these unique microvasculature characteristics warrant further investigation.
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Capilares/patologia , Doença da Artéria Coronariana/etiologia , Transplante de Coração/efeitos adversos , Remodelação Vascular , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Aloenxertos , Biópsia , Capilares/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Diástole , Ecocardiografia Doppler de Pulso , Humanos , Microcirculação , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
AIMS: Adjuvant heart failure (HF) drug therapy in patients undergoing chronic mechanical circulatory support (MCS) is often used in conjunction with a continuous-flow left ventricular assist device (LVAD), but its potential impact is not well defined. The objective of the present study was to examine the effects of conventional HF drug therapy on myocardial structure and function, peripheral organ function and the incidence of adverse events in the setting of MCS. METHODS AND RESULTS: Patients with chronic HF requiring LVAD support were prospectively enrolled. Paired myocardial tissue samples were obtained prior to LVAD implantation and at transplantation for histopathology. The Meds group comprised patients treated with neurohormonal blocking therapy (concurrent beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and aldosterone antagonist), and the No Meds group comprised patients on none of these. Both the Meds (n = 37) and No Meds (n = 44) groups experienced significant improvements in cardiac structure and function over the 6 months following LVAD implantation. The degree of improvement was greater in the Meds group, including after adjustment for baseline differences. There were no differences between the two groups in arrhythmias, end-organ injury, or neurological events. In patients with high baseline pre-LVAD myocardial fibrosis, treatment with HF drug therapy was associated with a reduction in fibrosis. CONCLUSIONS: Clinical and histopathological evidence showed that adjuvant HF drug therapy was associated with additional favourable effects on the structure and function of the unloaded myocardium that extended beyond the beneficial effects attributed to LVAD-induced unloading alone. Adjuvant HF drug therapy did not influence the incidence of major post-LVAD adverse events during the follow-up period.