Short-term effects of dapagliflozin on maximal functional capacity in heart failure with reduced ejection fraction (DAPA-VO2 ): a randomized clinical trial.

AIMS: This study aimed to evaluate the effect of dapagliflozin on 1 and 3-month maximal functional capacity in patients with stable heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: In this multicentre, randomized, double-blind clinical trial, 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin (n = 45) or placebo (n = 45). The primary outcome was a change in peak oxygen consumption (peakVO2 ) at 1 and 3 months. Secondary endpoints were changes at 1 and 3 months in 6-min walk test (6MWT) distance, quality of life (Minnesota Living with Heart Failure Questionnaire [MLHFQ]), and echocardiographic parameters (diastolic function, left chamber volumes, and left ventricular ejection fraction). We used linear mixed regression analysis to compare endpoint changes. Estimates were adjusted for multiple comparisons. The mean age was 67.1 ± 10.7 years, 69 (76.7%) were men, 29 (32.2%) had type 2 diabetes, and 80 (88.9%) were in New York Heart Association class II. Baseline means of peakVO2 , 6MWT and MLHFQ were 13.2 ± 3.5 ml/kg/min, 363 ± 110 m, and 23.1 ± 16.2, respectively. The median (25th-75th percentile) of N-terminal pro-brain natriuretic peptide was 1221 pg/ml (889-2100). Most patients were on treatment with sacubitril/valsartan (88.9%), beta-blockers (91.1%), and mineralocorticoid receptor antagonists (74.4%). PeakVO2 significantly increased in patients on treatment with dapagliflozin (1 month: +Δ 1.09 ml/kg/min, 95% confidence interval [CI] 0.14-2.04; p = 0.021, and 3 months: +Δ 1.06 ml/kg/min, 95% CI 0.07-2.04; p = 0.032). Similar positive findings were found when evaluating changes from baseline. No significant differences were observed in secondary endpoints. CONCLUSIONS: Among patients with stable HFrEF, dapagliflozin resulted in a significant improvement in peakVO2 at 1 and 3 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04197635.

Second-degree interatrial block: Brief review and concept.

The advanced interatrial block (A-IAB) (P ≥ 120 ms plus ± pattern in II, III and aVF) corresponds at atrial level, to right or left advanced bundle branch block at ventricular level, and it is well known that these patterns may be seen transiently in relation to taquicardia or bradycardia (tachycardia or bradycardia dependent right or left bundle branch block). We present for the first time, the same phenomenon at atrial level. In one case, the A-IAB appears in relation to tachycardization and in the other disappears during a pause induced by ventricular premature complex.

Early serum creatinine changes and outcomes in patients admitted for acute heart failure: the cardio-renal syndrome revisited.

BACKGROUND: The changes in renal function that occurred in patients with acute decompensated heart failure (ADHF) are prevalent, and have multifactorial etiology and dissimilar prognosis. To what extent the prognostic role of such changes may vary according to the presence of renal insufficiency at admission is not clear. Accordingly, we sought to determine whether early creatinine changes (ΔCr) (admission to 48-72 hours) had an effect on 1-year mortality relative to the presence of renal insufficiency at admission. METHODS: We included 705 consecutive patients admitted with the diagnosis of ADHF. Admission renal insufficiency was defined as serum creatinine ≥1.4mg/dl (A-RIcr) or estimated glomerular filtration rate <60ml/min/1.73m2 (A-RIGFR). Appropriate survival regression techniques were used. RESULTS: The mean age was 72.9±11.4 years and 51.2% were males. Patients with admission renal insufficiency (24.7% and 42.8% for A-RIcr and A-RIGFR, respectively) had higher prevalence of extreme values in ΔCr in either direction (increasing/decreasing). At 1-year follow-up, 114 (16.2%) deaths were registered. The multivariable analysis showed a significant interaction between admission renal insufficiency and ΔCr ( p=0.004 and p=0.019 for A-RIcr and A-RIGFR, respectively). In the presence of renal insufficiency, the continuum of ΔCr followed a positive and almost linear relationship with mortality risk. Conversely, in patients without renal insufficiency, those changes adopted a 'J-shape' trajectory with increased mortality at both ends of the curve distribution. CONCLUSIONS: In patients with ADHF the effect of ΔCr on 1-year mortality varied according to its magnitude and the presence of admission renal insufficiency. There was a graded-association with mortality when renal insufficiency was present on admission.

Analysis of blood pressure signal in patients with different ventricular ejection fraction using linear and non-linear methods.

Changes in the left ventricle function produce alternans in the hemodynamic and electric behavior of the cardiovascular system. A total of 49 cardiomyopathy patients have been studied based on the blood pressure signal (BP), and were classified according to the left ventricular ejection fraction (LVEF) in low risk (LR: LVEF>35%, 17 patients) and high risk (HR: LVEF≤35, 32 patients) groups. We propose to characterize these patients using a linear and a nonlinear methods, based on the spectral estimation and the recurrence plot, respectively. From BP signal, we extracted each systolic time interval (STI), upward systolic slope (BPsl), and the difference between systolic and diastolic BP, defined as pulse pressure (PP). After, the best subset of parameters were obtained through the sequential feature selection (SFS) method. According to the results, the best classification was obtained using a combination of linear and nonlinear features from STI and PP parameters. For STI, the best combination was obtained considering the frequency peak and the diagonal structures of RP, with an area under the curve (AUC) of 79%. The same results were obtained when comparing PP values. Consequently, the use of combined linear and nonlinear parameters could improve the risk stratification of cardiomyopathy patients.

Bioelectrical impedance vector analysis and clinical outcomes in patients with acute heart failure.

AIMS: Fluid overload is a hallmark in acute heart failure (AHF). Bioelectrical impedance vector analysis (BIVA) has emerged as a noninvasive method for quantifying patients' hydration. We aimed to evaluate the effect of BIVA hydration status (BHS) measured before discharge on mortality and rehospitalization for AHF. METHODS: We included 369 consecutive patients discharged from the cardiology department from a third-level hospital with a diagnosis of AHF. On the basis of BHS, patients were grouped into three categories: hyper-hydration (>74.3%), normo-hydration (72.7-74.3%) and dehydration (<72.7%). Appropriate survival techniques were used to evaluate the association between BHS and the risk of death and readmission for AHF. RESULTS: At a median follow-up of 12 months (interquartile range, IQR: 5-19), 80 (21.7%) deaths and 93 (25.2%) readmissions for AHF were registered. The mortality and readmission rates for the BHS categories were hyper-hydration (3.28 and 3.83 per 10 persons-years); normo-hydration (1.43 and 2.68 per 10 persons-years); and dehydration (2.24 and 2.53 per 10 persons-years) (P < 0.05 for all comparisons). In an adjusted analysis, BHS displayed a significant association with mortality (P = 0.004), with a higher mortality risk in those with hyperhydration. Likewise, BHS showed to linearly predict AHF-readmission risk [hazard ratio 1.06 (1.03-1.10); P = 0.001 per increase in 1%]. CONCLUSION: In patients admitted with AHF, BHS assessed before discharge was independently associated with the risk of death and AHF-readmission.

Cardiorespiratory and cardiovascular interactions in cardiomyopathy patients using joint symbolic dynamic analysis.

Cardiovascular diseases are the first cause of death in developed countries. Using electrocardiographic (ECG), blood pressure (BP) and respiratory flow signals, we obtained parameters for classifying cardiomyopathy patients. 42 patients with ischemic (ICM) and dilated (DCM) cardiomyopathies were studied. The left ventricular ejection fraction (LVEF) was used to stratify patients with low risk (LR: LVEF>35%, 14 patients) and high risk (HR: LVEF≤ 35%, 28 patients) of heart attack. RR, SBP and TTot time series were extracted from the ECG, BP and respiratory flow signals, respectively. The time series were transformed to a binary space and then analyzed using Joint Symbolic Dynamic with a word length of three, characterizing them by the probability of occurrence of the words. Extracted parameters were then reduced using correlation and statistical analysis. Principal component analysis and support vector machines methods were applied to characterize the cardiorespiratory and cardiovascular interactions in ICM and DCM cardiomyopathies, obtaining an accuracy of 85.7%.

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Orthotopic heart transplantation in patients with transposition of the great arteries.

Thanks to progress in cardiac surgery and cardiology, pediatric patients with complex congenital heart conditions who would previously have died are now reaching adulthood. Patients with transposition of the great arteries who have undergone atrial repair can present during follow-up with progression towards heart failure as a result of progressive systemic right ventricular failure. In this situation, heart transplantation is a possible therapeutic option. Anatomic abnormalities and the presence of intraatrial conduits ensure that transplantation must involve a number of technical modifications. Here, we present our experience during 1992-2004 with heart transplantations in four patients with transposition of the great arteries and atrial repair. There was no operative mortality. During follow-up (mean period, 75 months), there was one death due to chronic rejection. The other patients remain in New York Heart Association class I, with normally functioning grafts.

Trasplante cardiaco ortotópico en pacientes con trasposición de grandes vasos / Orthotopic Heart Transplantation in Patients With Transposition of the Great Arteries

Debido a la evolución de la cirugía cardiaca y la cardiología, los pacientes pediátricos que antaño fallecían a causa de cardiopatías congénitas actualmente llegan a la edad adulta. Los pacientes con transposición de grandes vasos y reparación fisiológica en el seguimiento pueden evolucionar hacia la insuficiencia cardiaca, como consecuencia del fallo progresivo del ventrículo derecho en posición sistémica. En esta situación, el trasplante cardiaco aparece como una posible alternativa terapéutica. Las alteraciones anatómicas y la presencia de conductos intraauriculares hacen que el trasplante precise de una serie de variaciones técnicas. Presentamos la experiencia en nuestro centro. Entre 1992 y 2004 se han realizado cuatro trasplantes cardiacos en transposición de grandes vasos y corrección fisiológica. No hubo mortalidad quirúrgica. Durante el seguimiento (media, 75 meses), se produjo una muerte por rechazo crónico. Los demás pacientes presentan clase I de la NYHA, con injerto normofuncionante

Thanks to progress in cardiac surgery and cardiology, pediatric patients with complex congenital heart conditions who would previously have died are now reaching adulthood. Patients with transposition of the great arteries who have undergone atrial repair can present during follow-up with progression towards heart failure as a result of progressive systemic right ventricular failure. In this situation, heart transplantation is a possible therapeutic option. Anatomic abnormalities and the presence of intraatrial conduits ensure that transplantation must involve a number of technical modifications. Here, we present our experience during 1992-2004 with heart transplantations in four patients with transposition of the great arteries and atrial repair. There was no operative mortality. During follow-up (mean period, 75 months), there was one death due to chronic rejection. The other patients remain in New York Heart Association class I, with normally functioning grafts

Characterization of periodic and non-periodic breathing pattern in chronic heart failure patients.

Periodic breathing (PB) has a high prevalence in chronic heart failure (CHF) patients with mild to moderate symptoms and poor ventricular function. This work proposes the analysis and characterization of the respiratory pattern to identify periodic breathing pattern (PB) and non-periodic breathing pattern (nPB) through the respiratory flow signal. The respiratory pattern analysis is based on the extraction and the study of the flow envelope signal. The flow envelope signal is modelled by an autoregressive model (AR) whose coefficients would characterize the respiratory pattern of each group. The goodness of the characterization is evaluated through a linear and non linear classifier applied to the AR coefficients. An adaptive feature selection is used before the linear and non linear classification, employing leave-one-out cross validation technique. With linear classification the percentage of well classified patients (8 PB and 18 nPB patients) is 84.6% using the statistically significant coefficients whereas with non linear classification, the percentage of well classified patients increase to more than 92% applying the best subset of coefficients extracted by a forward selection algorithm.

[Hemosiderin-laden macrophages count in sputum in diagnosis of dyspnea of heart origin]. / Recuento de hemosiderófagos en el esputo en el diagnóstico de la disnea de origen cardíaco.

BACKGROUND AND OBJECTIVE: The respiratory or heart origin of dyspnea is not always easy to find out using the available diagnostic tools. Many patients present both heart and lung diseases that cause dyspnea. The role of hemosiderin-laden macrophages count (HC) in sputum in this context has not been well settled so far. The objective was to describe the prediction usefulness of HC in patients suffering from dyspnea of heart origin, and to find out if HC changed after administering treatment. PATIENTS AND METHOD: HC was analyzed in 61 patients whose main symptom was dyspnea in the emergency department, and it was evaluated by means of clinical history, clinical course and performance of lung function tests and echocardiography. RESULTS: 35 patients were classified as having dyspnea of heart origin, 17 as having dyspnea of lung origin and 9 had dyspnea of both origins. The HC was higher in patients with dyspnea of heart origin 37% (95% CI, 26-47) or cardiopulmonary origin 30% (95% CI, 8-52) than in patients with dyspnea of lung origin 15% (95% CI, 4-27), and it remained higher despite administering treatment. The sensitivity (52%), specificity (88%), positive predictive value (92%) and negative predictive value (58%) was established for a 30% HC cutoff. The prediction model of heart origin dyspnea presented an area under the ROC curve of 0.978 (95% CI, 0.95-1). CONCLUSIONS: HC reflects the severity of pulmonary venocapillar disturbance, identifies the majority of patients suffering from current or past heart failure or severe cardiac dysfunction, and is useful for the prediction of dyspnea of heart origin. HC utility should focus on selected patients.

Recuento de hemosiderófagos en el esputo en el diagnóstico de la disnea de origen cardíaco / Hemosiderin-laden macrophages count in sputum in diagnosis of dyspnea of heart origin

FUNDAMENTO Y OBJETIVO: El origen respiratorio o cardíaco de la disnea no siempre es fácil de establecercon las herramientas diagnósticas disponibles. Muchos pacientes presentan a la vez procesoscardiológicos y pulmonares que la justifica. El papel que puede desempeñar el recuentode hemosiderófagos (RH) en esputo en este contexto no ha sido establecido suficientemente.El objetivo fue determinar la utilidad en la predicción y el diagnóstico del RH en pacientes condisnea de origen cardíaco, y si varía tras el tratamiento.PACIENTES Y MÉTODO: Hemos realizado el RH a 61 pacientes que consultaron por disnea en urgenciasy cuyo origen fue determinado por la historia clínica de urgencias, el curso clínico y la realizaciónde pruebas funcionales respiratorias y ecocardiograma.RESULTADOS: El RH fue superior en los pacientes con disnea de origen cardíaco (n = 35), 37%(intervalo de confianza [IC] del 95%, 26-47) o de origen cardiopulmonar (n = 9), 30% (IC del95%, 8-52) que el de origen respiratorio (n = 17), 15% (IC del 95%, 4-27). La sensibilidad(52%), especificidad (88%), valores predictivos positivo (92%) y negativo (58%) se determinaronpara un punto de corte del RH del 30%. El modelo de predicción de disnea de origen cardíaco,incluido el RH, presentó un área bajo la curva ROC de 0,978 (IC del 95%, 0,95-1).CONCLUSIONES: El RH refleja la gravedad de la alteración de la permeabilidad venocapilar pulmonar,identifica a la mayoría de los pacientes que presentan o han presentado disfunción o insuficienciacardíaca moderada o grave y predice la disnea de origen cardíaco. Su utilidad debecentrarse en casos seleccionados

BACKGROUND AND OBJECTIVE: The respiratory or heart origin of dyspnea is not always easy to findout using the available diagnostic tools. Many patients present both heart and lung diseasesthat cause dyspnea. The role of hemosiderin-laden macrophages count (HC) in sputum in thiscontext has not been well settled so far. The objective was to describe the prediction usefulnessof HC in patients suffering from dyspnea of heart origin, and to find out if HC changed afteradministering treatment.PATIENTS AND METHOD: HC was analized in 61 patients whose main symptom was dyspnea in theemergency department, and it was evaluated by means of clinical history, clinical course andperformance of lung function tests and echocardiography.RESULTS: 35 patients were classified as having dyspnea of heart origin, 17 as having dyspnea oflung origin and 9 had dyspnea of both origins. The HC was higher in patients with dyspnea ofheart origin 37% (95% CI, 26-47) or cardiopulmonary origin 30% (95% CI,, 8-52) than in patientswith dyspnea of lung origin 15% (95% CI, 4-27), and it remained higher despite administeringtreatment. The sensitivity (52%), specificity (88%), positive predictive value (92%)and negative predictive value (58%) was established for a 30% HC cutoff. The prediction modelof heart origin dyspnea presented an area under the ROC curve of 0.978 (95% CI, 0.95-1).CONCLUSIONS: HC reflects the severity of pulmonary venocapillar disturbance,identifies the majority of patients suffering from current or past heart failure or severe cardiacdysfunction, and is useful for the prediction of dyspnea of heart origin. HC utility should focuson selected patients

Detecting vulnerable plaque using peripheral blood: inflammatory and cellular markers.

The concept of the vulnerable patient has arrived. Enhanced diagnostic methods will eventually permit accurately finding and treating these patients and their disease. Clinical Cardiologists now recognize that coronary atherosclerosis is two pathophysiologically distinct syndromes: stable and unstable. Stable coronary syndromes result from fixed, severe stenoses limiting blood flow and causing secondary myocardial ischemia. The unstable acute coronary syndromes are frequently catastrophic and are pathophysiologically distinct. They result from different cell subsets causing vascular inflammatory syndromes rather than gradual lumen constriction by plaque. Though pathophysiologically distinct, they may show common pathophysiology when a ruptured plaque heals and progressively becomes a critical stenosis. For the present hs-CRP measurement is the strongest correlative factor for future clinical events due to arterial inflammation: myocardial infarction, unstable angina, stroke, and peripheral vascular disease in both diseased and apparently healthy, asymptomatic patients. The CRP plasma level also is the best risk assessment in patients with either stable or unstable angina, long term after myocardial infarction, and in patients undergoing revascularization therapies. One study showed the only independent cardiovascular risk indicators using multivariate, age adjusted and traditional risk analysis were CRP and Total/HDL cholesterol ratio. If CRP, IL-6, and ICAM-1 levels are added to lipid levels, risk assessment can be improved over lipids alone. The prevalence of high-risk subjects in the general population is low, amplifying diagnostic problems for vulnerable plaque. Since no test yet has high sensitivity or specificity, diagnostic errors are high, with many false positives and negatives. Sensitivity or specificity must be increased by developing a risk marker panel, or by simultaneously finding other markers that themselves are highly sensitive and specific for vulnerable plaque.

A critical role for elastin signaling in vascular morphogenesis and disease.

Vascular proliferative diseases such as atherosclerosis and coronary restenosis are leading causes of morbidity and mortality in developed nations. Common features associated with these heterogeneous disorders involve phenotypic modulation and subsequent abnormal proliferation and migration of vascular smooth muscle cells into the arterial lumen, leading to neointimal formation and vascular stenosis. This fibrocellular response has largely been attributed to the release of multiple cytokines and growth factors by inflammatory cells. Previously, we demonstrated that the disruption of the elastin matrix leads to defective arterial morphogenesis. Here, we propose that elastin is a potent autocrine regulator of vascular smooth muscle cell activity and that this regulation is important for preventing fibrocellular pathology. Using vascular smooth muscle cells from mice lacking elastin (Eln(-/-)), we show that elastin induces actin stress fiber organization, inhibits proliferation, regulates migration and signals via a non-integrin, heterotrimeric G-protein-coupled pathway. In a porcine coronary model of restenosis, the therapeutic delivery of exogenous elastin to injured vessels in vivo significantly reduces neointimal formation. These findings indicate that elastin stabilizes the arterial structure by inducing a quiescent contractile state in vascular smooth muscle cells. Together, this work demonstrates that signaling pathways crucial for arterial morphogenesis can play an important role in the pathogenesis and treatment of vascular disease.