Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the ...prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0-8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p < 0.001). This change in size was due to a reduction in the percentage of small HDL-P (54.6% vs. 60% for CV-death vs. alive; p < 0.001). HDL-C/P ratio was higher in the CV-death group (51.0 vs. 48.3, p < 0.001). HDL-Sz and HDL-C/P ratio were significantly associated with CV death after multivariable regression analysis (HR 1.22 95% CI 1.01-1.47, p = 0.041 and HR 1.04 95% CI 1.01-1.07, p = 0.008 respectively). HDL-Sz and HDL-C/P ratio are independent predictors of CV death in chronic HF patients.
Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline ...cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment.
Subjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression.
One hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months IQR 18.0-26.8 after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 300-450 mg/m2); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 1.17-2.30 per cycle), blood pressure ≥140/90mmHg (OR 5.36 1.73-17.61), body surface area (OR 2.08 1.36-3.20 per standard deviation (0.16m2) increase), and Trastuzumab therapy (OR 3.35 1.18-9.51). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 0.70-0.86.
We found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure-indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
Systolic pulmonary artery pressure (SPAP) and right heart adaptation in relation to pre-existing preload are often disregarded. To determine volume-related changes in the pulmonary-right ...ventricle (RV) unit and the preload dependence of its components, we analysed pulmonary haemodynamics and right ventricular performance, taking advantage of the plasma volume removal associated to haemodialysis (HD).
Methods and results
Fifty-three stable patients on chronic HD with LVEF > 50% and without heart failure were recruited (mean age 63.0 ± 12.4 years; 31.2% women; hypertension in 89% and diabetes in 53%) and evaluated just before and after HD (mean ultrafiltration volume 2.4 ± 0.7 l). SPAP from both times were available in 39 patients. After HD, SPAP decreased (42.2 ± 12.6 to 33.7 ± 11.6 mmHg,
p
< 0.001) without modification of non-invasive pulmonary vascular resistance (1.75 ± 0.44 to 1.75 ± 0.40 eWU,
p
= 0.94). Age and drop in the
E
/
e
ʹ ratio were the variables associated with greater reduction in PASP (
p
= 0.022 and
p
= 0.049, respectively). A significant reduction of right chamber sizes was observed, along with a diminution in measures of RV contractility, excluding RV longitudinal strain. Functional tricuspid regurgitation (FTR) diminution was observed in 26% of patients, occurring in every case with more than mild FTR. On multivariate analyses, left atrial size was the only predictor of pulmonary hypertension (defined as SPAP > 40 mmHg) (OR 1.29 (1.07–1.56),
p
= 0.006).
Conclusion
Rapid volemic changes may affect FTR grading, RV size and contractility, with RV longitudinal strain being less variable than conventional parameters. SPAP decreases after HD, and this reduction is related to age and greater diminution of the
E
/
e
ʹ ratio.
Graphic abstract
Small cardiac tissue engineering constructs show promise for limiting post-infarct sequelae in animal models. This study sought to scale-up a 2-cm2 preclinical construct into a human-size advanced ...therapy medicinal product (ATMP; PeriCord), and to test it in a first-in-human implantation.
The PeriCord is a clinical-size (12–16 cm2) decellularised pericardial matrix colonised with human viable Wharton's jelly-derived mesenchymal stromal cells (WJ-MSCs). WJ-MSCs expanded following good manufacturing practices (GMP) met safety and quality standards regarding the number of cumulative population doublings, genomic stability, and sterility. Human decellularised pericardial scaffolds were tested for DNA content, matrix stiffness, pore size, and absence of microbiological growth.
PeriCord implantation was surgically performed on a large non-revascularisable scar in the inferior wall of a 63-year-old male patient. Coronary artery bypass grafting was concomitantly performed in the non-infarcted area. At implantation, the 16-cm2 pericardial scaffold contained 12·5 × 106 viable WJ-MSCs (85·4% cell viability; <0·51 endotoxin units (EU)/mL). Intraoperative PeriCord delivery was expeditious, and secured with surgical glue. The post-operative course showed non-adverse reaction to the PeriCord, without requiring host immunosuppression. The three-month clinical follow-up was uneventful, and three-month cardiac magnetic resonance imaging showed ~9% reduction in scar mass in the treated area.
This preliminary report describes the development of a scalable clinical-size allogeneic PeriCord cardiac bioimplant, and its first-in-human implantation.
La Marató de TV3 Foundation, Government of Catalonia, Catalan Society of Cardiology, “La Caixa” Banking Foundation, Spanish Ministry of Science, Innovation and Universities, Institute of Health Carlos III, and the European Regional Development Fund.
Objective
To assess the arrhythmic safety profile of the adipose graft transposition procedure (AGTP) and its electrophysiological effects on post-myocardial infarction (MI) scar.
Background
...Myocardial repair is a promising treatment for patients with MI. The AGTP is a cardiac reparative therapy that reduces infarct size and improves cardiac function. The impact of AGTP on arrhythmogenesis has not been addressed.
Methods
MI was induced in 20 swine. Contrast-enhanced magnetic resonance (ce-MRI), electrophysiological study (EPS), and left-ventricular endocardial high-density mapping were performed 15 days post-MI. Animals were randomized 1:1 to AGTP or sham-surgery group and monitored with ECG-Holter. Repeat EPS, endocardial mapping, and ce-MRI were performed 30 days post-intervention. Myocardial SERCA2, Connexin-43 (Cx43), Ryanodine receptor-2 (RyR2), and cardiac troponin-I (cTnI) gene and protein expression were evaluated.
Results
The AGTP group showed a significant reduction of the total infarct scar, border zone and dense scar mass by ce-MRI (
p
= 0.04), and a decreased total scar and border zone area in bipolar voltage mapping (
p
< 0.001). AGTP treatment significantly reduced the area of very-slow conduction velocity (<0.2 m/s) (
p
= 0.002), the number of deceleration zones (
p
= 0.029), and the area of fractionated electrograms (
p
= 0.005). No differences were detected in number of induced or spontaneous ventricular arrhythmias at EPS and Holter-monitoring. SERCA2, Cx43, and RyR2 gene expression were decreased in the infarct core of AGTP-treated animals (
p
= 0.021,
p
= 0.018,
p
= 0.051, respectively).
Conclusion
AGTP is a safe reparative therapy in terms of arrhythmic risk and provides additional protective effect against adverse electrophysiological remodeling in ischemic heart disease.
The present study evaluates the safety and efficacy of the Adipose Graft Transposition Procedure (AGTP) as a biological regenerative innovation for patients with a chronic myocardial scar.
This ...prospective, randomized single-center controlled study included 10 patients with established chronic transmural myocardial scars. Candidates for myocardial revascularization were randomly allocated into two treatment groups. In the control arm (n=5), the revascularizable area was treated with CABG and the non-revascularizable area was left untouched. Patients in the AGTP-treated arm (n=5) were treated with CABG and the non-revascularizable area was covered by a biological adipose graft. The primary endpoint was the appearance of adverse effects derived from the procedure including hospital admissions and death, and 24-hour Holter monitoring arrhythmias at baseline, 1week, and 3 and 12months. Secondary endpoints of efficacy were assessed by cardiac MRI.
No differences in safety were observed between groups in terms of clinical or arrhythmic events. On follow-up MRI testing, participants in the AGTP-treated arm showed a borderline smaller left ventricular end systolic volume (LVESV; p=0.09) and necrosis ratio (p=0.06) at 3months but not at 12months. The AGTP-treated patient with the largest necrotic area and most dilated chambers experienced a noted improvement in necrotic mass size (−10.8%), and ventricular volumes (LVEDV: −55.2mL and LVESV: −37.8mL at one year follow-up) after inferior AGTP.
Our results indicate that AGTP is safe and may be efficacious in selected patients. Further studies are needed to assess its clinical value. (ClinicalTrials.org NCT01473433, AdiFlap Trial).
•The use of an autologous vascular adipose graft may be a safe alternative in patients with a chronic myocardial scar.•The Adipose Graft Transposition Procedure (AGTP) has autologous nature and is easy to implement.•Its translation to clinical practice should not be hampered by technical, economic, or ethical/social considerations.
The Adipose Graft Transposition Procedure (AGTP) is a new surgical technique for reducing the scar after a heart attack. It has been evaluated in 10 patients for the first time and has been proved to be safe. This technique consists on the use of the existing fat surrounding the heart that has beneficial properties. The procedure is easy for the surgeons to perform. The next step will be to test the efficacy in a larger population.
Purpose of the Review
The role of multimodality imaging in the evaluation of patients with aortic regurgitation is summarized in this review.
Recent Findings
The etiology (mechanism) of the aortic ...regurgitation and the severity of aortic regurgitation and hemodynamic consequences are key in the decision making of patients with severe aortic regurgitation. While echocardiography remains as the leading technique to assess all these parameters, other imaging techniques have become essential for the accurate assessment of aortic regurgitation severity and the timing of aortic intervention. The anatomic suitability of transcatheter aortic valve implantation in inoperable patients with severe aortic regurgitation is usually assessed with computed tomography.
Summary
Aortic regurgitation is a prevalent disease with various pathophysiological mechanisms that need a personalized treatment. The evaluation of the mechanism and severity of aortic regurgitation can be initially performed with echocardiography. Three-dimensional techniques, including echocardiography, have become very relevant for accurate assessment of the regurgitation severity and its hemodynamic consequences. Assessment of myocardial tissue characteristics with cardiac magnetic resonance is key in the risk stratification of patients and in the timing of aortic intervention. Computed tomography is important in the assessment of aortic dimensions and selection of patients for transcatheter aortic valve implantation.
El desarrollo del implante percutáneo de válvula aórtica ha revolucionado el tratamiento de la estenosis de válvula aórtica calcificada. Los pacientes ancianos a los que se consideraba inoperables ...ahora cuentan con un tratamiento eficaz y seguro que proporciona una mejor supervivencia. Además, las guías de práctica actuales tienden a recomendar una intervención más temprana para evitar las consecuencias irreversibles de la sobrecarga de presión de larga duración causada por la válvula aórtica estenótica. El momento adecuado para la intervención depende en gran medida de las técnicas de imagen que informan de la gravedad de la estenosis aórtica, pero también de las consecuencias hemodinámicas y el remodelado cardiaco. Si bien la fracción de eyección del ventrículo izquierdo sigue siendo uno de los principales parámetros funcionales para la estratificación del riesgo de los pacientes con estenosis aórtica grave, los avances en las técnicas de imagen han proporcionado nuevos parámetros estructurales y funcionales que permiten identificar a los pacientes que se beneficiarán de la intervención antes de que aparezcan síntomas o daño cardiaco irreversible. Además, el desarrollo de tratamientos médicos que pueden detener de manera efectiva la progresión de la estenosis aórtica depende en gran medida de la información que las técnicas de imagen aportan, y la caracterización de la actividad metabólica de la estenosis aórtica calcificada con técnicas de medicina nuclear o tomografía computarizada ha permitido monitorizar los efectos de esos tratamientos. El presente artículo de revisión brinda una visión actualizada de los avances en técnicas de imagen que caracterizan la fisiopatología y han cambiado el paradigma del tratamiento de la estenosis aórtica.
The advent of transcatheter aortic valve implantation has revolutionized the treatment of calcific aortic valve stenosis. Elderly patients who were previously considered inoperable have currently an efficacious and safe therapy that provides better survival. In addition, current practice guidelines tend to recommend earlier intervention to avoid the irreversible consequences of long-lasting pressure overload caused by the stenotic aortic valve. Appropriate timing of the intervention relies significantly on imaging techniques that provide information on the severity of the aortic stenosis as well as on the hemodynamic consequences and cardiac remodeling. While left ventricular ejection fraction remains one of the main functional parameters for risk stratification in patients with severe aortic stenosis, advances in imaging techniques have provided new structural and functional parameters that allow the identification of patients who will benefit from intervention before the occurrence of symptoms or irreversible cardiac damage. Furthermore, ongoing research aiming to identify the medical therapies that can effectively halt the progression of aortic stenosis relies heavily on imaging endpoints, and new imaging techniques that characterize the metabolic activity of calcific aortic stenosis have been proposed to monitor the effects of these therapies. The present review provides an up-to-date overview of the imaging advances that characterizes the pathophysiology and that have changed the management paradigm of aortic stenosis.
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