Home-based inspiratory muscle training for management of older patients with heart failure with preserved ejection fraction: does baseline inspiratory muscle pressure matter?

BACKGROUND: Heart failure with preserved ejection fraction is a clinical syndrome characterised by reduced exercise capacity. Some evidence has shown that a simple and home-based programme of inspiratory muscle training offers promising results in terms of aerobic capacity improvement in patients with heart failure with preserved ejection fraction. This study aimed to investigate whether the baseline inspiratory muscle function predicts the changes in aerobic capacity (measured as peak oxygen uptake; peak VO2) after a 12-week home-based programme of inspiratory muscle training in patients with heart failure with preserved ejection fraction. METHODS: A total of 45 stable symptomatic patients with heart failure with preserved ejection fraction and New York Heart Association II-III received a 12-week home-based programme of inspiratory muscle training between June 2015 and December 2016. They underwent cardiopulmonary exercise testing and measurements of maximum inspiratory pressure pre and post-inspiratory muscle training. Maximum inspiratory pressure and peak VO2 were registered in both visits. Multivariate linear regression analysis was used to assess the association between changes in peak VO2 (Δ-peakVO2) and baseline predicted maximum inspiratory pressure (pp-MIP). RESULTS: The median (interquartile range) age was 73 (68-77) years, 47% were women and 35.6% displayed New York Heart Association III. The mean peak VO2 at baseline and Δ-peakVO2 post-training were 10.4±2.8 ml/min/kg and +2.2±1.3 ml/min/kg (+21.3%), respectively. The median (interquartile range) of pp-MIP and Δ-MIP were 71% (64-92) and 39.2 (26.7-80.4) cmH2O, respectively. After a multivariate analysis, baseline pp-MIP was not associated with Δ-peakVO2 (ß coefficient 0.005, 95% confidence interval -0.009-0.019, P=0.452). CONCLUSIONS: In symptomatic and deconditioned older patients with heart failure with preserved ejection fraction, a home-based inspiratory muscle training programme improves aerobic capacity regardless of the baseline maximum inspiratory pressure.

Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction: The TRAINING-HF Trial.

INTRODUCTION AND OBJECTIVES: Despite the prevalence of heart failure with preserved ejection fraction (HFpEF), there is currently no evidence-based effective therapy for this disease. This study sought to evaluate whether inspiratory muscle training (IMT), functional electrical stimulation (FES), or a combination of both (IMT + FES) improves 12- and 24-week exercise capacity as well as left ventricular diastolic function, biomarker profile, and quality of life in HFpEF. METHODS: A total of 61 stable symptomatic patients (New York Heart Association II-III) with HFpEF were randomized (1:1:1:1) to receive a 12-week program of IMT, FES, or IMT + FES vs usual care. The primary endpoint of the study was to evaluate change in peak exercise oxygen uptake at 12 and 24 weeks. Secondary endpoints were changes in quality of life, echocardiogram parameters, and prognostic biomarkers. We used a mixed-effects model for repeated-measures to compare endpoints changes. RESULTS: Mean age and peak exercise oxygen uptake were 74 ± 9 years and 9.9 ± 2.5mL/min/kg, respectively. The proportion of women was 58%. At 12 weeks, the mean increase in peak exercise oxygen uptake (mL/kg/min) compared with usual care was 2.98, 2.93, and 2.47 for IMT, FES, and IMT + FES, respectively (P < .001) and this beneficial effect persisted after 6 months (1.95, 2.08, and 1.56; P < .001). Significant increases in quality of life scores were found at 12 weeks (P < .001). No other changes were found. CONCLUSIONS: In HFpEF patients with low aerobic capacity, IMT and FES were associated with a significant improvement in exercise capacity and quality of life. This trial was registered at ClinicalTrials.gov (Identifier: NCT02638961)..

Inspiratory Muscle Training and Functional Electrical Stimulation for Treatment of Heart Failure With Preserved Ejection Fraction: Rationale and Study Design of a Prospective Randomized Controlled Trial.

Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent form of heart failure in developed countries. Regrettably, there is no evidence-based effective therapy for HFpEF. We seek to evaluate whether inspiratory muscle training, functional electrical stimulation, or a combination of both can improve exercise capacity as well as left ventricular diastolic function, biomarker profile, quality of life (QoL), and prognosis in patients with HFpEF. A total of 60 stable symptomatic patients with HFpEF (New York Heart Association class II-III/IV) will be randomized (1:1:1:1) to receive a 12-week program of inspiratory muscle training, functional electrical stimulation, a combination of both, or standard care alone. The primary endpoint of the study is change in peak exercise oxygen uptake; secondary endpoints are changes in QoL, echocardiogram parameters, and prognostic biomarkers. As of March 21, 2016, thirty patients have been enrolled. Searching for novel therapies that improve QoL and autonomy in the elderly with HFpEF has become a health care priority. We believe that this study will add important knowledge about the potential utility of 2 simple and feasible physical interventions for the treatment of advanced HFpEF.

Evaluation of the complexity of myocardial activation during ventricular fibrillation. An experimental study.

INTRODUCTION AND OBJECTIVES: An experimental model is used to analyze the characteristics of ventricular fibrillation in situations of variable complexity, establishing relationships among the data produced by different methods for analyzing the arrhythmia. METHODS: In 27 isolated rabbit heart preparations studied under the action of drugs (propranolol and KB-R7943) or physical procedures (stretching) that produce different degrees of change in the complexity of myocardial activation during ventricular fibrillation, use was made of spectral, morphological, and mapping techniques to process the recordings obtained with epicardial multielectrodes. RESULTS: The complexity of ventricular fibrillation assessed by mapping techniques was related to the dominant frequency, normalized spectral energy, signal regularity index, and their corresponding coefficients of variation, as well as the area of the regions of interest identified on the basis of these parameters. In the multivariate analysis, we used as independent variables the area of the regions of interest related to the spectral energy and the coefficient of variation of the energy (complexity index=-0.005×area of the spectral energy regions -2.234×coefficient of variation of the energy+1.578; P=.0001; r=0.68). CONCLUSIONS: The spectral and morphological indicators and, independently, those derived from the analysis of normalized energy regions of interest provide a reliable approach to the evaluation of the complexity of ventricular fibrillation as an alternative to complex mapping techniques.

Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure.

AIMS: Recent observations in chronic stable heart failure suggest that high-dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diuretics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF). METHODS AND RESULTS: We analysed 1389 consecutive patients discharged for AHF. CA125 and BUN were measured at a mean of 72 ± 12 h after admission. HDLDs (≥120 mg/day in furosemide equivalent dose) were interacted to a four-level variable according to CA125 (>35 U/mL) and BUN (above the median), and related to all-cause mortality. At a median follow-up of 21 months, 561 (40.4%) patients died. The use of HDLDs was independently associated with increased mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01-1.50], but this association was not homogeneous across CA125-BUN categories (P for interaction <0.001). In patients with normal CA125, use of HDLDs was associated with high mortality if BUN was above the median (HR 2.29, 95% 1.51-3.46), but not in those with BUN below the median (HR 1.22, 95% CI 0.73-2.04). Conversely, in patients with high CA125, HDLDs showed an association with increased survival if BUN was above the median (HR 0.73, 95% CI 0.55-0.98) but was associated with increased mortality in those with BUN below the median (HR 1.94, 95% CI 1.36-2.76). CONCLUSION: The risk associated with HDLDs in patients after hospitalization for AHF was dependent on the levels of BUN and CA125. The information provided by these two biomarkers may be helpful in tailoring the dose of loop diuretics at discharge for AHF.

Impacto pronóstico de una estrategia invasiva en el síndrome coronario agudo sin elevación del segmento ST según la presencia o no de disfunción sistólica / Effect of invasive treatment on prognosis in non-ST-segment elevation acute coronary syndrome with or without systolic dysfunction

Introducción y objetivos. Escasa evidencia respalda la implantación de una estrategia invasiva (EI) en pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST) y disfunción sistólica (DS). El objetivo de este trabajo es evaluar el impacto pronóstico atribuible a una EI en sujetos con SCASEST según tengan DS o no. Métodos. Se incluyó a 972 pacientes consecutivos ingresados por SCASEST (descenso del segmento ST y/o elevación de troponina I). Se definió la DS como fracción de eyección < 50% mediante ecocardiografía transtorácica. El objetivo principal fue la muerte o infarto a largo plazo. Se analizó el impacto pronóstico atribuible a una EI mediante regresión de Cox. Resultados. El 23,4% presentó DS. Un total de 303 (31%) pacientes alcanzaron el objetivo primario, hecho que fue más frecuente en los pacientes con DS (el 49,8 frente al 25,5%; p < 0,001). La realización de coronariografías y procedimientos de revascularización fue similar entre pacientes con DS y pacientes con fracción de eyección ≥ 50% (el 59 frente al 63,4%; p = 0,239 y el 38,3 frente al 38,8%; p = 0,9). Tras un minucioso ajuste multivariable que incluyó un índice de propensión, se observó un impacto pronóstico diferencial atribuible a la realización de una coronariografía según hubiera DS o no (interacción, p = 0,01). Así, el beneficio del cateterismo fue evidente en los pacientes con DS ( hazard ratio [HR] = 0,47; intervalo de confianza [IC] del 95%, 0,3-0,75; p = 0,001), pero no en aquellos con fracción de eyección ≥ 50% (HR = 0,9; IC del 95%, 0,63-1,29; p = 0,567). Conclusiones. La presencia de DS permite la identificación de los SCASEST que más se benefician de aplicar una EI (AU)

Introduction and objectives. Few data are available on the use of invasive treatment in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) and systolic dysfunction. The aim of this study was to determine the effect of invasive treatment on the prognosis of patients with NSTEACS, with or without systolic dysfunction. Methods. The study included 972 consecutive patients admitted for NSTEACS (i.e. ST-segment depression or an elevated troponin-I level). Systolic dysfunction was defined as an ejection fraction <50 on transthoracic echocardiography the primary long-term endpoint was death or myocardial infarction effect of invasive treatment prognosis evaluated by cox regression analysis results overall 23 4 patients had systolic dysfunction and 303 31 2 reached which more frequent in those with 49 8 vs 25 5 p <.001). Usage of coronary angiography and revascularization procedures were similar in patients with systolic dysfunction and those with an ejection fraction ≥50% (59% vs. 63.4%; P=.239; and 38.3% vs. 38.8%; P=.9; respectively). Detailed adjusted multivariate analysis, including the use of a propensity score, demonstrated that coronary angiography had a differential effect on prognosis depending on the presence or absence of systolic dysfunction (interaction, P=.01). Catheterization was clearly beneficial in patients with systolic dysfunction (hazard ratio [HR]=0.47; 95% confidence interval [CI], 0.3-0.75; P=.001) but not in those with an ejection fraction ≥50% (HR=0.9; 95% CI, 0.63-1.29; P=.567). Conclusions. The presence of systolic dysfunction identifies those patients with NSTEACS who will benefit most from invasive treatment (AU)

Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts.

Stretch induces modifications in myocardial electrical and mechanical activity. Besides the effects of substances that block the stretch-activated channels, other substances could modulate the effects of stretch through different mechanisms that affect Ca(2+) handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na(+)/Ca(2+) exchanger blocker KB-R7943, propranolol, and the adenosine A(2) receptor antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF) produced by acute myocardial stretching. VF recordings were obtained with two epicardial multiple electrodes before, during, and after local stretching in four experimental series: control (n = 9), KB-R7943 (1 microM, n = 9), propranolol (1 microM, n = 9), and SCH-58261 (1 microM, n = 9). Both the Na(+)/Ca(2+) exchanger blocker KB-R7943 and propranolol induced a significant reduction (P < 0.001 and P < 0.05, respectively) in the dominant frequency increments produced by stretching with respect to the control and SCH-58261 series (control = 49.9%, SCH-58261 = 52.1%, KB-R7943 = 9.5%, and propranolol = 12.5%). The median of the activation intervals, the functional refractory period, and the wavelength of the activation process during VF decreased significantly under stretch in the control and SCH-58261 series, whereas no significant variations were observed in the propranolol and KB-R7943 series, with the exception of a slight but significant decrease in the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and propranolol induced a significant reduction in the activation maps complexity increment produced by stretch with respect to the control and SCH-58261 series. In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na(+)/Ca(2+) exchanger blocker KB-R7943 and by propranolol but not by the adenosine A(2) receptor antagonist SCH-58261.

Efectos de la estreptomicina en las modificaciones de la activacion miocardica durante la fibrilacion ventricular inducidas por el estiramiento / Effect of streptomycin on stretch-induced change in myocardial activation during ventricular fibrillation

Se ha evaluado si las modificaciones en la activación miocárdica durante la fibrilación ventricular producidas por el estiramiento agudo pueden ser contrarrestadas por un bloqueador de los receptores sensibles al estiramiento. En 16 corazones aislados de conejo, se ha analizado la refractariedad y la frecuencia de activación durante la fibrilación ventricular antes, durante y después de producir un estiramiento agudo localizado en la pared libre del ventrículo izquierdo, en ausencia (serie A, n = 8) o en presencia (serie B, n = 8) de estreptomicina 200 μmol. Durante la perfusión de estreptomicina (serie B), tanto basalmente como durante y después del estiramiento, la fibrilación ventricular ha sido más lenta que en la serie A (frecuencia dominante basal, 13 ± 2 Hz frente a 16 ± 2 Hz; p < 0,005; frecuencia dominante estiramiento, 14 ± 2 Hz frente a 19 ± 3 Hz; p < 0,005). La estreptomicina ha atenuado las modificaciones electrofisiológicas producidas por el estiramiento y ha tenido efecto directo en la refractariedad y la frecuencia de activación durante la fibrilación ventricular (AU)

The aim of this study was to determine whether the changes in myocardial activation pattern resulting from acute stretching during ventricular fibrillation can be counteracted by administering a compound that blocks receptors sensitive to stretch. The study involved 16 isolated rabbit hearts, in which refractoriness and activation frequency during ventricular fibrillation were measured before, during and after localized acute stretching of the left ventricular free wall, either without (series A, n=8) or with (series B, n=8) the presence of streptomycin, 200 μmol. At baseline and during and after stretching, ventricular fibrillation was slower with streptomycin perfusion in series B than in series A (dominant frequency at baseline, 13±2 Hz vs. 16±2 Hz, respectively; P<.005; dominant frequency with stretching, 14±2 Hz vs. 19±3 Hz, respectively; P<.005). Streptomycin attenuated the electrophysiological changes produced by stretching and had a direct effect on refractoriness and activation frequency during ventricular fibrillation (AU)

[Influence of recording mode (unipolar or bipolar) on the spectral characteristics of epicardial recordings in ventricular fibrillation. An experimental study]. / Influencia del tipo de registro (unipolar o bipolar) en las características espectrales de los registros epicárdicos de la fibrilación ventricular. Estudio experimental.

INTRODUCTION AND OBJECTIVES: The aim of this study was to examine the hypothesis that the recording mode (i.e., unipolar or bipolar) affects the information obtained using spectral analysis techniques during ventricular fibrillation by carrying out an experiment using epicardial electrodes. METHODS: Recordings of ventricular fibrillation were obtained in 29 isolated rabbit hearts using a multiple-electrode probe located on the left ventricular free wall. The parameter values obtained in the frequency domain (by Fourier analysis) using unipolar or bipolar electrodes, different interelectrode distances, and different orientations (i.e., horizontal, vertical or diagonal) were compared. RESULTS: Changing the recording mode (i.e., unipolar to bipolar) or the interelectrode distance significantly altered the mean frequency (P< .0001) and the normalized energy of the spectrum (+/-1 Hz) around the dominant frequency (P< .05), though the changes were small relative to the dominant frequency. Cross-spectral analysis showed that the coherence between unipolar recordings decreased as the interelectrode distance increased, while the opposite occurred with the coherence between unipolar and bipolar recordings. The two coherences were inversely correlated such that the greater the former coherence, the less the coherence between unipolar and bipolar recordings (r=0.29; P< .0001; n=348). CONCLUSIONS: The recording mode (i.e., unipolar or bipolar) used influenced the information obtained using spectral analysis techniques from epicardial recordings of ventricular fibrillation. Differences were observed in the mean frequency and in the frequency distribution, but they were very small relative to the dominant frequency.

Influencia del tipo de registro (unipolar o bipolar) en las características espectrales de los registros epicárdicos de la fibrilación ventricular. Estudio experimental / Influence of recording mode (unipolar or bipolar) on the spectral characteristics of epicardial recordings in ventricular fibrillation. An experimental study

Introducción y objetivos. Se evalúa la hipótesis de que el tipo de registro (unipolar o bipolar) influye en la información obtenida mediante técnicas espectrales durante la fibrilación ventricular en un modelo experimental que utiliza electrodos epicárdicos. Métodos. En 29 corazones aislados de conejo se obtienen registros de la fibrilación ventricular con un electrodo múltiple situado en la pared libre del ventrículo izquierdo. Se comparan los parámetros obtenidos en el dominio de la frecuencia (análisis de Fourier) al utilizar electrodos unipolares o bipolares con varias separaciones entre los electrodos en distintas direcciones (horizontal, vertical o diagonales). Resultados. La modalidad de registro (unipolar o bipolar) y la separación entre los electrodos han introducido diferencias significativas en la frecuencia media (p < 0,0001) y en la energía normalizada del espectro alrededor de la frecuencia dominante (± 1 Hz) (p < 0,05), pero éstas han sido mínimas al considerar la frecuencia dominante. En el análisis espectral cruzado, se ha observado que la coherencia entre los registros unipolares disminuye al aumentar la separación entre los electrodos, mientras que ocurre lo contrario al analizar la coherencia entre los unipolares y los bipolares. Ambas coherencias se correlacionan inversamente, de tal modo que cuanto mayor es la primera menor es la de los unipolares respecto a los bipolares (r = 0,29; p < 0,0001; n = 348). Conclusiones. El tipo de registro utilizado (unipolar o bipolar) introduce variaciones en la información obtenida mediante técnicas espectrales en los registros epicárdicos de la fibrilación ventricular. Estas diferencias se observan en la frecuencia media y en la distribución de frecuencias del espectro, pero son muy pequeñas al considerar la frecuencia dominante (AU)

Introduction and objectives. The aim of this study was to examine the hypothesis that the recording mode (i.e., unipolar or bipolar) affects the information obtained using spectral analysis techniques during ventricular fibrillation by carrying out an experiment using epicardial electrodes. Methods. Recordings of ventricular fibrillation were obtained in 29 isolated rabbit hearts using a multiple-electrode probe located on the left ventricular free wall. The parameter values obtained in the frequency domain (by Fourier analysis) using unipolar or bipolar electrodes, different interelectrode distances, and different orientations (i.e., horizontal, vertical or diagonal) were compared. Results. Changing the recording mode (i.e., unipolar to bipolar) or the interelectrode distance significantly altered the mean frequency (P<.0001) and the normalized energy of the spectrum (±1 Hz) around the dominant frequency (P<.05), though the changes were small relative to the dominant frequency. Cross-spectral analysis showed that the coherence between unipolar recordings decreased as the interelectrode distance increased, while the opposite occurred with the coherence between unipolar and bipolar recordings. The two coherences were inversely correlated such that the greater the former coherence, the less the coherence between unipolar and bipolar recordings (r=0.29; P<.0001; n=348). Conclusions. The recording mode (i.e., unipolar or bipolar) used influenced the information obtained using spectral analysis techniques from epicardial recordings of ventricular fibrillation. Differences were observed in the mean frequency and in the frequency distribution, but they were very small relative to the dominant frequency (AU)

Modification of ventricular fibrillation activation patterns induced by local stretching.

INTRODUCTION: We hypothesize that local modifications in electrophysiological properties, when confined to zones of limited extent, induce few changes in the global activation process during ventricular fibrillation (VF). To test this hypothesis, we produced local electrophysiological modifications by stretching a circumscribed zone of the left ventricular wall in an experimental model of VF. METHODS AND RESULTS: In 23 Langendorff-perfused rabbit hearts frequency, time-frequency and time-domain techniques were used to analyze the VF recordings obtained with two epicardial multiple electrodes before, during, and after local stretching produced with a left intraventricular device. Acute local stretching accelerated VF in the stretched zone reversibly and to a variable degree, depending on the magnitude of stretch and the time elapsed from its application. In the half time (5 minutes) of the analyzed period, a longitudinal lengthening of 12.1 +/- 4.5% (vertical axis) and 11.8 +/- 6.2% (horizontal axis) in the stretched zone produced an increase in the dominant frequency (DFr) (15.2 +/- 1.9 versus 18.8 +/- 2.5 Hz, P < 0.0001), a decrease in mean VV interval (63 +/- 8 versus 53 +/- 6 msec, P < 0.001), and an increase in the complexity of the activation maps-with more areas of conduction block and more breakthrough patterns (23% versus 37%, P < 0.01), without significant changes in the percentages of complete reentry patterns (9% versus 9%, ns). Simultaneously, in the nonstretched zone, no variations were observed in the DFr (15.2 +/- 2.1 versus 15.3 +/- 2.5 Hz, ns), mean VV intervals (66 +/- 8 versus 65 +/- 8 msec, ns), or types and percentages of maps with breakthrough (25% versus 20%, ns) or reentry patterns (12% versus 8%, ns). No significant correlation was observed between the DFr in the two zones (R = 0.24, P = 0.40). CONCLUSION: Local stretching increases the electrophysiological heterogeneity of myocardium and accelerates and increases the complexity of VF in the stretched area, without significantly modifying the occurrences of the types of VF activation patterns in the nonstretched zone.

Effects of acute reduction of temperature on ventricular fibrillation activation patterns.

Because of its electrophysiological effects, hypothermia can influence the mechanisms that intervene in the sustaining of ventricular fibrillation. We hypothesized that a rapid and profound reduction of myocardial temperature impedes the maintenance of ventricular fibrillation, leading to termination of the arrhythmia. High-resolution epicardial mapping (series 1; n = 11) and transmural recordings of ventricular activation (series 2; n = 10) were used to analyze ventricular fibrillation modification during rapid myocardial cooling in Langendorff-perfused rabbit hearts. Myocardial cooling was produced by the injection of cold Tyrode into the left ventricle after induction of ventricular fibrillation. Temperature and ventricular fibrillation dominant frequency decay fit an exponential model to arrhythmia termination in all experiments, and both parameters were significantly correlated (r = 0.70, P < 0.0001). Termination of the arrhythmia occurred preferentially in the left ventricle and was associated with a reduction in conduction velocity (-60% in left ventricle and -54% in right ventricle; P < 0.0001) and with activation maps predominantly exhibiting a single wave front, with evidence of wave front extinction. We conclude that a rapid reduction of temperature to <20 degrees C terminates ventricular fibrillation after producing an important depression in myocardial conduction.