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OBJECTIVE: To review the pathology of the mitral valve (MV) and long-term outcomes of surgery in patients with Marfan syndrome (MFS). PATIENTS AND METHODS: From 1988 through 2020, 60 patients with MFS had surgery to correct mitral regurgitation (MR): 19 had isolated MV surgery, 32 had combined MV and aortic root surgery, and 9 had MV surgery after aortic root surgery. Follow-up was complete for a median of 16.1 years. RESULTS: MV pathology was myxomatous degeneration in all patients and of advanced degree in 78.6% with bileaflet prolapse in 65.5%, mitral annulus disjunction in 57.5%, and mitral annulus calcification in 8.2% of patients. The MV was repaired in 47 patients and replaced in 13. Kaplan-Meier estimates of cumulative mortality at 20 years 21.3% for all patients, 6.7% after MV repair, and 57.8% after replacement (P < .001). MV reoperations were performed in 5 patients: 2 after repair and 3 after replacement. The cumulative incidence rate of reoperations on the MV was 3.8% at 10 years and 11.0% at 20 years in the entire cohort. Among 47 patients who had MV repair, moderate MR developed in 11 patients and severe in 2. Both patients with severe MR underwent MV reoperation. The cumulative incidence rate of recurrent moderate or severe MR after MV repair was 20.4% at 10 years, and 36.5% at 20 years. CONCLUSIONS: MV repair was associated with better survival than MV replacement, but recurrent MR after repair occurred in approximately one-third of the patients at 20 years after surgery.
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Objective: Functional assessment of hearts during ex-vivo heart perfusion is not well-established. Conventional intraventricular balloon methods for large animals sacrifice the mitral valve. This study assessed the effectiveness of the modified intraventricular balloon method in comparison with other modalities used during working mode in juvenile pigs. Methods: Following asphyxia circulatory arrest, hearts were ischemic for 15 minutes and then reperfused on an ex-vivo device for 2 hours before switching to working mode. Left ventricular pressure was continuously measured during reperfusion by a saline-filled balloon fixated in the left atrium. Spearman Correlation Coefficients with linear regression lines with confidence intervals were analyzed. Results: Maximum dp/dt at 90 minutes of reperfusion and minimum dp/dt at 60 minutes of reperfusion showed a moderate positive correlation to that in working mode, respectively (Rs = 0.61, P = .04 and Rs = 0.60, P = .04). At 60 minutes of reperfusion, minimum dp/dt showed moderate positive correlation to tau (Rs = 0.52, P = .08). Myocardial oxygen consumption during reperfusion consistently decreased at least 30% compared to working mode (at 90 minutes as the highest during reperfusion, 3.3 ± 0.8; in working mode, 5.6 ± 1.4, mLO2/min/100 g, P < .001). Conclusions: Functional parameters of contractility and relaxation measured during reperfusion by the modified balloon method showed significant correlations to respective parameters in working mode. This mitral valve sparing technique can be used to predict viability and ventricular function in the early phase of ex-vivo heart perfusion without loading the heart during working mode.
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The safety of continuing human epidermal growth factor receptor 2 (HER2)-targeted therapy in women with mild cardiotoxicity remains unclear. We performed a retrospective matched cohort study of 14 patients with human epidermal growth factor receptor 2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, nested within the Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI (EMBRACE-MRI) trial. Among patients who developed cardiotoxicity and were treated with heart failure therapy, we compared those who had trastuzumab therapy interrupted to a matched cohort who continued trastuzumab therapy. By a median of 2.5 years of follow-up, no significant differences were present between the groups in the proportion with magnetic resonance imaging-measured left ventricular ejection fraction < 40%, magnetic resonance imaging-measured left ventricular volumes, left ventricular ejection fraction, edema, fibrotic markers, cardiopulmonary fitness, or quality of life.
La question de savoir s'il est sûr de poursuivre le traitement par un médicament ciblant le récepteur 2 du facteur de croissance épidermique humain (HER2) en présence d'une légère cardiotoxicité chez la femme demeure controversée. Nous avons réalisé une étude de cohortes appariées rétrospective auprès de 14 patientes atteintes d'un cancer du sein positif pour le HER2 qui recevaient un traitement séquentiel par l'anthracycline et le trastuzumab, dans le cadre du programme EMBRACE-MRI ( E valuation of M yocardial Changes During Br east A denocarcinoma Therapy to Detect C ardiotoxicity E arlier With MRI ). Parmi les patientes ayant développé une cardiotoxicité et ayant reçu un traitement pour l'insuffisance cardiaque, nous avons comparé celles dont le traitement par le trastuzumab a été interrompu à une cohorte appariée ayant poursuivi ce traitement. Après un suivi médian de 2,5 ans, aucune différence significative n'avait été observée entre les groupes en ce qui concerne le pourcentage de patientes dont la fraction d'éjection ventriculaire gauche était inférieure à 40 % à l'imagerie par résonance magnétique (IRM), le volume ventriculaire gauche à l'IRM, la fraction d'éjection ventriculaire gauche, l'Ådème, les marqueurs fibrotiques, la bonne forme physique de l'appareil cardio-pulmonaire ou la qualité de vie.
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BACKGROUND: Guideline-directed medical therapy (GDMT) remains underutilized in patients with heart failure with reduced ejection fraction, leading to morbidity and mortality. OBJECTIVES: The Medly Titrate (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration) study was an open-label, randomized controlled trial to determine whether remote medication titration for patients with heart failure with reduced ejection fraction was more effective than usual care (UC). METHODS: In this study, 108 patients were randomized to remote GDMT titration through the Medly heart failure program (n = 56) vs UC (n = 52). The primary outcome was the proportion of patients completing GDMT titration at 6 months. Secondary outcomes included the number of clinic visits and time required to achieve titration, patient health outcomes, and health care utilization, including urgent clinic/emergency department visits and hospitalization. RESULTS: At 6 months, GDMT titration was completed in 82.1% (95% CI: 71.2%-90.8%) of patients in the intervention arm vs 53.8% in UC (95% CI: 41.1%-67.7%; P = 0.001). Remote titration required fewer in-person (1.62 ± 1.09 vs 2.42 ± 1.65; P = 0.004) and virtual clinic visits (0.50 ± 1.08 vs 1.29 ± 1.86; P = 0.009) to complete titration. Median time to optimization was shorter with remote titration (3.42 months [Q1-Q3: 2.99-4.04 months] vs 5.47 months [Q1-Q3: 4.14-7.33 months]; P < 0.001). The number of urgent clinic/emergency department visits (incidence rate ratio of remote vs control groups: 0.90 [95% CI: 0.53-1.56]; P = 0.70) were similar between groups, with a reduction in all-cause hospitalization with remote titration (incidence rate ratio: 0.55 [95% CI: 0.31-0.97]; P = 0.042). CONCLUSIONS: Remote titration of GDMT in heart failure with reduced ejection fraction was effective, safe, feasible, and increased the proportion of patients achieving target doses, in a shorter period of time with no excess adverse events compared with UC. (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration [Medly Titrate]; NCT04205513).
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Volume SistólicoRESUMO
Background: Diaphragm atrophy can contribute to dyspnea in patients with heart failure (HF) with its link to central neurohormonal overactivation. HF medications that cross the blood-brain barrier could act centrally and improve respiratory function, potentially alleviating diaphragmatic atrophy. Therefore, we compared the benefit of central- vs peripheral-acting HF drugs on respiratory function, as assessed by a single cardiopulmonary exercise test (CPET) and outcomes in HF patients. Methods: A retrospective study was conducted of 624 ambulatory adult HF patients (80% male) with reduced left ventricular ejection fraction ≤ 40% and a complete CPET, followed at a single institution between 2001 and 2017. CPET parameters, and the outcomes all-cause death, a composite endpoint (all-cause death, need for left ventricular assist device, heart transplantation), and all-cause and/or HF hospitalizations, were compared in patients receiving central-acting (n = 550) vs peripheral-acting (n = 74) drugs. Results: Compared to patients who receive peripheral-acting drugs, patients who receive central-acting drugs had better respiratory function (peak breath-by breath oxygen uptake [VO2], P = 0.020; forced expiratory volume in 1 second [FEV1], P = 0.007), and ventilatory efficiency (minute ventilation / carbon dioxide production [VE/VCO2], P < 0.001; end-tidal carbon dioxide tension [PETCO2], P = 0.015; and trend for forced vital capacity [FVC], P = 0.056). Many of the associations between the CPET parameters and drug type remained significant after multivariate adjustment. Moreover, patients receiving central-acting drugs had fewer composite events (P = 0.023), and HF hospitalizations (P = 0.044), although significance after multivariant correction was not achieved, despite the hazard ratio being 0.664 and 0.757, respectively. Conclusions: Central-acting drugs were associated with better respiratory function as measured by CPET parameters in HF patients. This could extend to clinically meaningful composite outcomes and hospitalizations but required more power to be definitive in linking to drug effect. Central-acting HF drugs show a role in mitigating diaphragm weakness.
Contexte: L'atrophie du diaphragme peut contribuer à la dyspnée chez les personnes atteintes d'insuffisance cardiaque (IC), compte tenu de son lien avec la suractivation neuro-hormonale centrale. Or, les médicaments contre l'IC qui franchissent la barrière hématoencéphalique pourraient exercer une action centrale, améliorer la respiration et ainsi éventuellement atténuer l'atrophie du diaphragme. C'est pourquoi nous avons voulu comparer, au moyen d'une seule épreuve d'effort cardiopulmonaire (EECP), les effets bénéfiques exercés par des médicaments à action périphérique et des médicaments à action centrale sur la fonction respiratoire, de même que l'issue des patients atteints d'IC auxquels ils ont été administrés. Méthodologie: Nous avons réalisé une étude rétrospective auprès de 624 adultes ambulatoires atteints d'IC (80 % d'hommes) dont la fraction d'éjection ventriculaire gauche était réduite (≤ 40 %), qui se sont prêtés à une EECP complète et qui ont été suivis dans le même établissement entre 2001 et 2017. Les paramètres de l'EECP et la mortalité toutes causes confondues, un critère d'évaluation composé (décès toutes causes confondues, nécessité de recourir à un dispositif d'assistance ventriculaire gauche, transplantation cardiaque), et les hospitalisations toutes causes confondues et/ou liées à l'IC ont été comparés entre les patients qui recevaient des médicaments à action centrale (n = 550) et ceux qui recevaient des médicaments à action périphérique (n = 74). Résultats: Comparativement aux patients ayant reçu des médicaments à action périphérique, ceux qui ont reçu des médicaments à action centrale ont bénéficié d'une meilleure fonction respiratoire (consommation maximale d'oxygène [VO2], p = 0,020; volume expiratoire maximal par seconde [VEMS], p = 0,007) et d'une meilleure efficacité ventilatoire (ventilation minute/production de dioxyde de carbone [VE/VCO2], p < 0,001; pression partielle de dioxyde de carbone en fin d'expiration [PETCO2], p = 0,015; et tendance de la capacité vitale forcée [CVF], p = 0,056). De plus, bon nombre des associations entre les paramètres de l'EECP et le type de médicament sont demeurées significatives après ajustement multivarié. Les patients qui ont reçu des médicaments à action centrale ont également présenté moins d'événements faisant partie du critère d'évaluation composé (p = 0,023) et moins d'hospitalisations liées à l'IC (p = 0,044), même si la différence après correction multivariée n'a pas été significative et que les rapports de risques étaient respectivement de 0,664 et de 0,757. Conclusions: Les médicaments à action centrale ont été associés à une meilleure fonction respiratoire, mesurée à l'aide des paramètres d'une EECP, chez les patients atteints d'IC. Ce résultat pourrait également s'appliquer au critère d'évaluation composé et aux hospitalisations, mais une étude plus puissante est nécessaire pour établir un lien cliniquement significatif avec l'effet des médicaments. Les médicaments à action centrale contre l'IC ont donc un rôle à jouer dans la correction de la faiblesse du diaphragme.