RESUMO
SIGNIFICANCE STATEMENT: The effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on regional tubular sodium handling is poorly understood in humans. In this study, empagliflozin substantially decreased lithium reabsorption in the proximal tubule (PT) (a marker of proximal tubular sodium reabsorption), a magnitude out of proportion to that expected with only inhibition of sodium-glucose cotransporter-2. This finding was not driven by an "osmotic diuretic" effect; however, several parameters changed in a manner consistent with inhibition of the sodium-hydrogen exchanger 3. The large changes in proximal tubular handling were acutely buffered by increased reabsorption in both the loop of Henle and the distal nephron, resulting in the observed modest acute natriuresis with these agents. After 14 days of empagliflozin, natriuresis waned due to increased reabsorption in the PT and/or loop of Henle. These findings confirm in humans that SGLT2i have complex and important effects on renal tubular solute handling. BACKGROUND: The effect of SGLT2i on regional tubular sodium handling is poorly understood in humans but may be important for the cardiorenal benefits. METHODS: This study used a previously reported randomized, placebo-controlled crossover study of empagliflozin 10 mg daily in patients with diabetes and heart failure. Sodium handling in the PT, loop of Henle (loop), and distal nephron was assessed at baseline and day 14 using fractional excretion of lithium (FELi), capturing PT/loop sodium reabsorption. Assessments were made with and without antagonism of sodium reabsorption through the loop using bumetanide. RESULTS: Empagliflozin resulted in a large decrease in sodium reabsorption in the PT (increase in FELi=7.5%±10.6%, P = 0.001), with several observations suggesting inhibition of PT sodium hydrogen exchanger 3. In the absence of renal compensation, this would be expected to result in approximately 40 g of sodium excretion/24 hours with normal kidney function. However, rapid tubular compensation occurred with increased sodium reabsorption both in the loop ( P < 0.001) and distal nephron ( P < 0.001). Inhibition of sodium-glucose cotransporter-2 did not attenuate over 14 days of empagliflozin ( P = 0.14). However, there were significant reductions in FELi ( P = 0.009), fractional excretion of sodium ( P = 0.004), and absolute fractional distal sodium reabsorption ( P = 0.036), indicating that chronic adaptation to SGLT2i results primarily from increased reabsorption in the loop and/or PT. CONCLUSIONS: Empagliflozin caused substantial redistribution of intrarenal sodium delivery and reabsorption, providing mechanistic substrate to explain some of the benefits of this class. Importantly, the large increase in sodium exit from the PT was balanced by distal compensation, consistent with SGLT2i excellent safety profile. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov ( NCT03027960 ).
Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Lítio , Estudos Cross-Over , Néfrons , Insuficiência Cardíaca/tratamento farmacológico , Diuréticos , GlucoseRESUMO
BACKGROUND: Left ventricular (LV) systolic dysfunction worsens outcomes in patients undergoing percutaneous coronary intervention (PCI). The objective of this study, therefore, was to evaluate outcomes of pLVAD-supported high-risk PCI (HRPCI) patients according to LV ejection fraction (LVEF). METHODS: Patients from the PROTECT III study undergoing pLVAD-supported HRPCI were stratified according to baseline LVEF: severe LV dysfunction (LVEF <30%), mild and moderate LV dysfunction (LVEF ≥30% to <50%), or preserved LV function (LVEF ≥50%). Major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization), and PCI-related complications were assessed at 90 days and mortality was assessed at 1-year. RESULTS: From March 2017 to March 2020, 940 patients had evaluable baseline LVEF recorded in the study database. Patients with preserved LV function were older, more frequently presented with myocardial infarction, and underwent more left main PCI and atherectomy. Immediate PCI-related coronary complications were infrequent (2.7%, overall), similar between groups (P = 0.98), and not associated with LVEF. Unadjusted 90-day MACCE rates were similar among LVEF groups; however, as a continuous variable, LVEF was associated with both 90-day MACCE (adj.HR per 5% 0.89, 95% CI [0.80, 0.98], P = 0.018) and 1-year mortality (adj.HR per 5% 0.84 [0.78, 0.90], P <0.0001). CONCLUSIONS: Patients who underwent pLVAD-supported HRPCI exhibited low incidence of PCI-related complications, regardless of baseline LVEF. However, LVEF was associated with 90-day MACCE and 1-year mortality.
Assuntos
Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico , Função Ventricular Esquerda , Resultado do Tratamento , Infarto do Miocárdio/complicações , Doença da Artéria Coronariana/complicaçõesRESUMO
PURPOSE OF THE REVIEW: Cardiac allograft vasculopathy (CAV) is a progressive fibroproliferative disease which occurs after heart transplantation and is associated with significant long-term morbidity and mortality. Currently available strategies including statins, mammalian target of rapamycin (mTOR) inhibitors, and revascularization, have limited overall effectiveness in treating this pathology once the disease process is established. mTOR inhibitors, while effective when used early in the disease process, are not well tolerated, and hence not routinely used in post-transplant care. RECENT DATA: Recent work on rodent models have given us a novel mechanistic understanding of effects of ascorbic acid in preventing CAV. TET methyl cytosine dioxygenase2 (TET2) reduces vascular smooth muscle cell (VSMC) apoptosis and intimal thickening. TET2 is repressed by interferon γ (IFNγ) in the setting of CAV. Ascorbic acid has been shown to promote TET2 activity and attenuate allograft vasculopathy in animal models and CAV progression in a small clinical trial. SUMMARY: CAV remains a challenging disease process and needs better preventative strategies. Ascorbic acid improves endothelial dysfunction, reduces reactive oxygen species, and prevents development of intimal hyperplasia by preventing smooth muscle cell apoptosis and hyperproliferation. Further large-scale randomized control studies of ascorbic acid are needed to establish the role in routine post-transplant management.
Assuntos
Cardiopatias , Transplante de Coração , Doenças Vasculares , Animais , Humanos , Ácido Ascórbico/uso terapêutico , Cardiopatias/etiologia , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/etiologia , Doenças Vasculares/prevenção & controle , Transplante Homólogo , Transplante de Coração/efeitos adversos , Aloenxertos , MamíferosRESUMO
PURPOSE OF REVIEW: The number of dual organ transplantations (DOT) are steadily increasing over the past few years. This is both a reflection of increasing complexity and advanced disease process in the patients and greater transplant center experience with performing dual organ transplants. Due to lack of standardization of the process, there remains significant center-based variability in patient selection, perioperative and long-term management of these patients. RECENT FINDINGS: Overall posttransplant outcomes for DOT have been acceptable with some immunological advantages because of partial tolerance offered by the second organ. These achievements should, however, be balanced with the ethical implications of bypassing the patients who are listed for single organ transplantation because of the preferential allocation of organs for DOT. SUMMARY: The field of DOT is expanding rapidly, with good long-term outcomes. There is an urgent need for guidelines to standardize the process of patient selection and listing dual organ transplantation.
Assuntos
Transplante de Coração , Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Órgãos/efeitos adversos , Listas de EsperaRESUMO
BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are recommended for patients with cardiac sarcoidosis (CS) with an indication for pacing, prior ventricular arrhythmias, cardiac arrest, or left ventricular ejection fraction <35%, but data on outcomes are limited. METHODS: Using data from the National Cardiovascular Data Registry ICD Registry between April 1, 2010 and December 31, 2015, we evaluated a propensity matched cohort of CS patients implanted with ICDs versus non-ischemic cardiomyopathies (NICM). We compared mortality using Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS: We identified 1,638 patients with CS and 8,190 propensity matched patients with NICM. The rate of death at 1 and 2 years was similar in patients with CS and patients with NICM (5.2% vs 5.4%, P = 0.75 and 9.0% vs 9.3%, P = 0.72, respectively). After adjusting for other covariates, patients with CS had similar mortality at 2 years after ICD implantations compared with NICM patients (RR 1.03, 95% CI 0.87-1.23). Among patients with CS, multivariable logistic regression identified 6 factors significantly associated with increased 2-year mortality: presence of heart failure (HR 1.92, 95% CI 1.44-3.22), New York Heart Association (NYHA) Class III heart failure (HR 1.68, 95% CI 1.16-2.45), NYHA Class IV heart failure (HR 3.08, 95% CI 1.49-6.39), atrial fibrillation/flutter (HR 1.66, 95% CI 1.17-2.35), chronic lung disease (HR 1.64, 95% CI 1.17-2.29), creatinine >2.0 mg/dL (HR 4.07, 95% CI 2.63-6.30), and paced rhythm (HR 2.66, 95% CI 1.07-6.59). CONCLUSION: Mortality following ICD implantation was similar in CS patients compared with propensity matched NICM patients. Presence of heart failure, NYHA class, atrial fibrillation/flutter, chronic lung disease, renal dysfunction, and paced rhythm at time of implantation were all predictors of increased 2-year mortality among CS patients with ICDs.
Assuntos
Fibrilação Atrial , Desfibriladores Implantáveis , Insuficiência Cardíaca , Miocardite , Sarcoidose , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Insuficiência Cardíaca/terapia , Humanos , Estudos Retrospectivos , Fatores de Risco , Sarcoidose/complicações , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: Inferior vena cava (IVC) measurements correlate only modestly with right atrial pressure (RAP). Part of this inaccuracy is due to the high compliance of the venous system, where a large change in blood volume may result in only a small change in pressure. As such, the information provided by the IVC may be different rather than redundant. METHODS AND RESULTS: We analyzed patients in the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial who had both pulmonary artery catheter and IVC measurements at baseline (nâ¯=â¯108). There was only a modest correlation between baseline RAP and IVC diameter (râ¯=â¯0.41; P < 0.001). Hemoconcentration, defined as an increase in hemoglobin levels between admission and discharge, was correlated with decrease in IVC diameter (râ¯=â¯0.35; Pâ¯=â¯0.02) but not with a decrease in RAP (râ¯=â¯0.01; Pâ¯=â¯0.95). When patients had both IVC and RAP measurements that were below the median, survival rates were superior to the rates of those who had only 1 measurement below the median, and when both rates were above the median, patients fared the worst (Pâ¯=â¯0.002). CONCLUSION: IVC and RAP have limited correlation with each another, and changes in intravascular volume appear to correlate better with IVC diameter rather than with RAP. Furthermore, complementary information is provided by pressure and volume assessments in acute decompensated heart failure.
Assuntos
Insuficiência Cardíaca , Veia Cava Inferior , Pressão Atrial , Cateterismo de Swan-Ganz , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Humanos , Veia Cava Inferior/diagnóstico por imagemRESUMO
AIMS: In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown. METHODS AND RESULTS: Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13-17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47). CONCLUSION: On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.
Assuntos
Insuficiência Cardíaca , Sódio , Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Natriurese , Inibidores de Simportadores de Cloreto de Sódio e PotássioRESUMO
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors improve heart failure-related outcomes. The mechanisms underlying these benefits are not well understood, but diuretic properties may contribute. Traditional diuretics such as furosemide induce substantial neurohormonal activation, contributing to the limited improvement in intravascular volume often seen with these agents. However, the proximal tubular site of action of the sodium-glucose cotransporter-2 inhibitors may help circumvent these limitations. METHODS: Twenty patients with type 2 diabetes mellitus and chronic, stable heart failure completed a randomized, placebo-controlled crossover study of empagliflozin 10 mg daily versus placebo. Patients underwent an intensive 6-hour biospecimen collection and cardiorenal phenotyping at baseline and again after 14 days of study drug. After a 2-week washout, patients crossed over to the alternate therapy with the above protocol repeated. RESULTS: Oral empagliflozin was rapidly absorbed as evidenced by a 27-fold increase in urinary glucose excretion by 3 hours (P<0.0001). Fractional excretion of sodium increased significantly with empagliflozin monotherapy versus placebo (fractional excretion of sodium, 1.2±0.7% versus 0.7±0.4%; P=0.001), and there was a synergistic effect in combination with bumetanide (fractional excretion of sodium, 5.8±2.5% versus 3.9±1.9%; P=0.001). At 14 days, the natriuretic effect of empagliflozin persisted, resulting in a reduction in blood volume (-208 mL [interquartile range, -536 to 153 mL] versus -14 mL [interquartile range, -282 to 335 mL]; P=0.035) and plasma volume (-138 mL, interquartile range, -379 to 154±453 mL; P=0.04). This natriuresis was not, however, associated with evidence of neurohormonal activation because the change in norepinephrine was superior (P=0.02) and all other neurohormones were similar (P<0.34) during the empagliflozin versus placebo period. Furthermore, there was no evidence of potassium wasting (P=0.20) or renal dysfunction (P>0.11 for all biomarkers), whereas both serum magnesium (P<0.001) and uric acid levels (P=0.008) improved. CONCLUSIONS: Empagliflozin causes significant natriuresis, particularly when combined with loop diuretics, resulting in an improvement in blood volume. However, off-target electrolyte wasting, renal dysfunction, and neurohormonal activation were not observed. This favorable diuretic profile may offer significant advantage in the management of volume status in patients with heart failure and may represent a mechanism contributing to the superior long-term heart failure outcomes observed with these agents. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03027960.
Assuntos
Compostos Benzidrílicos , Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Diuréticos , Glucosídeos , Insuficiência Cardíaca , Idoso , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/farmacocinética , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/urina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/urina , Diuréticos/administração & dosagem , Diuréticos/farmacocinética , Método Duplo-Cego , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/urina , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Sensitized patients awaiting heart transplantation spend a longer time on the waitlist and have higher mortality. We are now able to further characterize sensitization by discriminating antibodies against class I and II, but the differential impact of these has not been assessed systematically. METHODS AND RESULTS: Using United Network for Organ Sharing data (2004-2015), we analyzed 17,361 adult heart transplant patients whose class I and II panel reactive antibodies were reported. Patients were divided into 4 groups: class I and II ≤25% (group 1); class I ≤25% and class II Ë25% (group 2); class II ≤25% and class I >25% (group 3); and both class I and II >25% (group 4). Outcomes assessed were treated rejection at 1-year mortality, all-cause mortality, and rejection-related mortality. Compared with group 1, only group 4 was associated with a higher risk of treated rejection at 1 year (odds ratio 1.31, 95% confidence interval [CI] 1.05-1.64), all-cause mortality (hazard ratio 1.24, 95% CI 1.06-1.46), and mortality owing to rejection (subhazard ratio 1.84, 95% CI 1.18-2.85), whereas groups 2 and 3 were not (P > .05). CONCLUSIONS: Combined elevation in class I and II panel reactive antibodies seem to increase the risk of treated rejection and all-cause mortality, whereas risk with isolated elevation is unclear.
Assuntos
Insuficiência Cardíaca , Transplante de Coração , Adulto , Rejeição de Enxerto/epidemiologia , Humanos , Isoanticorpos , Estudos Retrospectivos , Fatores de RiscoAssuntos
Insuficiência da Valva Mitral , Insuficiência da Valva Tricúspide , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Tricúspide/complicações , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/cirurgiaRESUMO
Cardiac allograft vasculopathy (CAV) is a progressive fibroproliferative disease, which contributes to significant morbidity and mortality during long-term follow-up after heart transplantation. Mammalian target of rapamycin (mTOR) inhibitors have favorable effects on endothelial function and reduce intimal proliferation, and their early use after transplantation has been associated with a reduction in the risk of development and progression of CAV. However, there are conflicting reports on the efficacy of these agents in treating established CAV. Most of the data until recently have been based on short-term follow-up, and CAV was assessed by changes in intravascular ultrasound. In this study, we review the mechanism of action of mTOR inhibitors and their protective role in CAV and summarize some of the recent literature, which include long-term follow-up using this class of medications.
Assuntos
Transplante de Coração , Sirolimo , Aloenxertos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/efeitos adversos , Humanos , Serina-Treonina Quinases TORRESUMO
PURPOSE OF REVIEW: The purpose of this review is to provide an update on cardiac sarcoidosis (CS) and to discuss the current recommendations and progress in diagnosis and management of this disease. Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Cardiac involvement is seen in at least 25% and is associated with poor prognosis. Manifestations of cardiac sarcoidosis (CS) can vary from presence of silent myocardial granulomas, which may lead to sudden death, to symptomatic conduction abnormalities, ventricular arrhythmias, and heart failure. RECENT FINDINGS: We discuss newer imaging modalities such as cardiac magnetic resonance imaging and positron emission tomography in conjunction with clinical criteria increasingly used for diagnosing and prognosticating patients with CS. Immunosuppression (primarily corticosteroids) is recommended for treatment of CS; however, its efficacy has never been proven in prospective randomized studies. The role of imaging to guide the use of immunotherapy is unknown. Cardiac sarcoidosis continues to challenge clinicians due to its protean presentations, lack of diagnostic standards, and data for risk stratification and treatment. There is a need for prospective, randomized controlled trials to understand how best to diagnose and treat cardiac sarcoidosis.
Assuntos
Cardiomiopatias , Cardiopatias , Sarcoidose , Cardiomiopatias/diagnóstico por imagem , Cardiopatias/diagnóstico por imagem , Cardiopatias/terapia , Humanos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Sarcoidose/diagnósticoRESUMO
BACKGROUND: Renal dysfunction (RD) is a potent risk factor for death in patients with cardiovascular disease. This relationship may be causal; experimentally induced RD produces findings such as myocardial necrosis and apoptosis in animals. Cardiac transplantation provides an opportunity to investigate this hypothesis in humans. METHODS AND RESULTS: Cardiac transplantations from the United Network for Organ Sharing registry were studied (n = 23,056). RD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2). RD was present in 17.9% of donors and 39.4% of recipients. Unlike multiple donor characteristics, such as older age, hypertension, or diabetes, donor RD was not associated with recipient death or retransplantation (age-adjusted hazard ratio [HR] = 1.00, 95% confidence interval [CI] 0.94-1.07, P = .92). Moreover, in recipients with RD the highest risk for death or retransplantation occurred immediately posttransplant (0-30 day HR = 1.8, 95% CI 1.54-2.02, P < .001) with subsequent attenuation of the risk over time (30-365 day HR = 0.92, 95% CI 0.77-1.09, P = .33). CONCLUSIONS: The risk for adverse recipient outcomes associated with RD does not appear to be transferrable from donor to recipient via the cardiac allograft, and the risk associated with recipient RD is greatest immediately following transplant. These observations suggest that the risk for adverse outcomes associated with RD is likely primarily driven by nonmyocardial factors.
Assuntos
Aloenxertos/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/efeitos adversos , Insuficiência Renal/fisiopatologia , Doadores de Tecidos , Adulto , Sobrevivência de Enxerto , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Transplante de Coração/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/complicações , Reoperação , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Accurate assessment of aortic valve (AV) stenosis (AS) on transthoracic echocardiogram is crucial for appropriate clinical management. However, discordance between aortic valve area (AVA) and Doppler can complicate the diagnosis of severe AS in low-gradient (LG) AS phenotypes. METHODS: We reviewed 220 consecutive patients with suspected severe AS and AVA ≤1.0 cm2 on transthoracic echocardiogram who were evaluated for transcatheter AV replacement (TAVR) within a large health system from 2015 to 2019. We compared AV calcium score and aorto-mitral angle (AMA) on 3-chamber views from ECG-gated cardiovascular CT among patients with high-gradient (HG) AS (N = 19), paradoxical low-flow low-gradient (PLFLG) AS (N = 24) and normal-flow low-gradient (NFLG) AS (N = 14). RESULTS: All groups had comparable age, comorbidities, and AV calcium scores. Compared to patients with HG AS (mean AMA 120 ± 10°), those with PLFLG AS (104 ± 12°; p < 0.001) and NFLG AS (106 ± 13°; p = 0.008) had narrower mean AMA values on cardiovascular CT. CONCLUSION: LG AS patients have significantly narrower AMA than HG AS patients on cardiovascular CT. Due to difficulty obtaining parallel Doppler alignment, narrower AMA may contribute to AVA-Doppler discordance on echocardiogram. These findings emphasize the need for additional information in the setting of LG AS.
Assuntos
Estenose da Valva Aórtica , Humanos , Estenose da Valva Aórtica/diagnóstico por imagem , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Valva Mitral/diagnóstico por imagem , Valva Aórtica/diagnóstico por imagem , Ecocardiografia/métodos , Tomografia Computadorizada por Raios X/métodos , Índice de Gravidade de Doença , Substituição da Valva Aórtica Transcateter/métodosRESUMO
BACKGROUND: Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated. METHODS: We evaluated 2,077 subjects from the Surveillance HeartCare Outcomes Registry registry who were enrolled between 2018 and 2021 and had verified biopsy data and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. The incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LRs+) were calculated, and biopsy rates over time were analyzed. RESULTS: The incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive, and 9.2% for dual-positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive, and 35.4% for dual-positive results. The LR+ for ACR was 1.37, 2.91, and 3.90 for GEP positive, dd-cfDNA positive, and dual-positive testing, respectively. From 2018 to 2021, biopsies performed between 2 and 12-months post-transplant declined from 5.9 to 5.3 biopsies/patient, and second-year biopsy rates declined from 1.5 to 0.9 biopsies/patient. At 2 years, survival was 94.9%, and only 2.7% had graft dysfunction. CONCLUSIONS: Dual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. The use of dual noninvasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction.
Assuntos
Rejeição de Enxerto , Transplante de Coração , Sistema de Registros , Humanos , Transplante de Coração/efeitos adversos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Doença Aguda , Adulto , Incidência , Perfilação da Expressão Gênica , Biópsia , Ácidos Nucleicos Livres/sangue , Seguimentos , Estados Unidos/epidemiologiaRESUMO
AIMS: Loop diuretics may exacerbate cardiorenal syndrome (CRS) in heart failure (HF). Direct sodium removal (DSR) using the peritoneal membrane, in conjunction with complete diuretic withdrawal, may improve CRS and diuretic resistance. METHODS AND RESULTS: Patients with HF requiring high-dose loop diuretics were enrolled in two prospective, single-arm studies: RED DESERT (n = 8 euvolaemic patients), and SAHARA (n = 10 hypervolaemic patients). Loop diuretics were withdrawn, and serial DSR was utilized to achieve and maintain euvolaemia. At baseline, participants required a median 240 mg (interquartile range [IQR] 200-400) oral furosemide equivalents/day, which was withdrawn in all participants during DSR (median time of DSR 4 weeks [IQR 4-6]). Diuretic response (queried by formal 40 mg intravenous furosemide challenge and 6 h urine sodium quantification) increased substantially from baseline (81 ± 37 mmol) to end of DSR (223 ± 71 mmol, p < 0.001). Median time to re-initiate diuretics was 87 days, and the median re-initiation dose was 8% (IQR 6-10%) of baseline. At 1 year, diuretic dose remained substantially below baseline (30 [IQR 7.5-40] mg furosemide equivalents/day). Multiple dimensions of kidney function such as filtration, uraemic toxin excretion, kidney injury, and electrolyte handling improved (p < 0.05 for all). HF-related biomarkers including N-terminal pro-B-type natriuretic peptide, carbohydrate antigen-125, soluble ST2, interleukin-6, and growth differentiation factor-15 (p < 0.003 for all) also improved. CONCLUSIONS: In patients with HF and diuretic resistance, serial DSR therapy with loop diuretic withdrawal was feasible and associated with substantial and persistent improvement in diuretic resistance and several cardiorenal parameters. If replicated in randomized controlled studies, DSR may represent a novel therapy for diuretic resistance and CRS. CLINICAL TRIAL REGISTRATION: RED DESERT (NCT04116034), SAHARA (NCT04882358).
Assuntos
Resistência a Medicamentos , Furosemida , Insuficiência Cardíaca , Sódio , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Cardiorrenal/tratamento farmacológico , Síndrome Cardiorrenal/fisiopatologia , Diuréticos/uso terapêutico , Diuréticos/administração & dosagem , Furosemida/administração & dosagem , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Estudos Prospectivos , Sódio/urina , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagemRESUMO
Mechanical circulatory support (MCS) is becoming the mainstay of therapy for patients with advanced heart failure, both for patients needing support as a bridge to transplantation and for those who require the device as a destination therapy. As more and more devices are implanted, there is a need to address effective discharge planning, arrange appropriate follow-up, anticipate and address complications, and develop strategies for long-term care. In this article, we will discuss issues surrounding discharge and challenges of managing patients with MCS in the outpatient setting.
Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Serviços Hospitalares de Assistência Domiciliar/organização & administração , Hospitalização , Humanos , Assistência de Longa Duração/organização & administração , Alta do PacienteRESUMO
A complex case of inferior wall infarction with ventricular septal defect and severe tricuspid valve regurgitation due to acute papillary muscle rupture in a 65 year-old male is described. This constellation of pathological lesions and the surgical approach to the repair have not been previously described.
Assuntos
Comunicação Interventricular , Choque Cardiogênico , Insuficiência da Valva Tricúspide , Idoso , Comunicação Interventricular/etiologia , Comunicação Interventricular/patologia , Comunicação Interventricular/cirurgia , Humanos , Masculino , Choque Cardiogênico/complicações , Choque Cardiogênico/patologia , Choque Cardiogênico/cirurgia , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/patologia , Insuficiência da Valva Tricúspide/cirurgiaRESUMO
OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is used to support patients in severe cardiogenic shock. In the absence of recovery, these patients may need to be listed for heart transplant (HT), which offers the best long-term prognosis. However, posttransplantation mortality is significantly elevated in patients who receive ECMO. The objective of the present study was to describe and risk-stratify different profiles of patients listed for HT supported by ECMO. METHODS: Patients listed for HT in the United Network for Organ Sharing database were analyzed. The primary outcome was 1-year survival and was assessed in patients bridged to transplant with ECMO (ECMOBTT) and patients who were previously supported on ECMO but had it removed before HT (ECMOREMOVED). RESULTS: Among 65,636 adult candidates listed for HT (between 2001 and 2017), 712 were supported on ECMO, 292 of whom (41%) underwent HT (ECMOBTT, n = 202; ECMOREMOVED, n = 90). Most of the patients with ECMOREMOVED were transplanted with a ventricular assist device. In ECMOBTT, recipient age (each 10-year increase), time on the waitlist (both defined as minor risk factors), need for dialysis, and need for mechanical ventilation (both defined as major risk factors) were independent predictors of mortality. ECMOREMOVED and ECMOBTT with no risk factors showed 1-year survival comparable to that in patients who were never supported on ECMO. Compared with patients who were never on ECMO, patients in ECMOBTT group with minor risk factors, 1 major risk factor, and 2 major risk factors had ~2-, ~5-, and >10-fold greater 1-year mortality, respectively (P < .05). CONCLUSIONS: The HT recipients in the ECMOREMOVED and ECMOBTT groups with no risk factors showed similar survival as the HT recipients who were never supported on ECMO. In the ECMOBTT group, posttransplantation mortality increased significantly with increasing risk factors.