Impaired Chronotropic Response Research Articles

P3425Persistence of impaired chronotropic responses after the completion of phase II cardiac rehabilitation predicts a poor long-term cardiovascular prognosis

P3425Persistence of impaired chronotropic responses after the completion of phase II cardiac rehabilitation predicts a poor long-term cardiovascular prognosis

Impaired chronotropic response to physical activities in heart failure patients

BackgroundWhile exercise-based cardiac rehabilitation has a beneficial effect on heart failure hospitalization and mortality, it is limited by the presence of chronotropic incompetence (CI) in some patients. This study explored the feasibility of using wearable devices to assess impaired chronotropic response in heart failure patients.MethodsForty patients with heart failure (left ventricular ejection fraction, LVEF: 44.6 ± 5.8; age: 54.4 ± 11.7) received ECG Holter and accelerometer to monitor heart rate (HR) and physical activities during symptom-limited treadmill exercise testing, 6-min hall walk (6MHW), and 24-h daily living. CI was defined as maximal HR during peak exercise testing failing to reach 70% of age-predicted maximal HR (APMHR, 220 – age). The correlation between HR and physical activities in Holter-accelerometer recording was analyzed.ResultsOf 40 enrolled patients, 26 were able to perform treadmill exercise testing. Based on exercise test reports, 13 (50%) of 26 patients did not achieve at least 70% of APMHR (CI patients). CI patients achieved a lower % APMHR (62.0 ± 6.3%) than non-CI patients who achieved 72.0 ± 1.2% of APMHR (P < 0.0001). When Holter-accelerometer recording was used to assess chronotropic response, the percent APMHR achieved during 6MHW and physical activities was significantly lower in CI patients than in non-CI patients. CI patients had a significantly shorter 6MHW distance and less physical activity intensity than non-CI patients.ConclusionThe study found impaired chronotropic response in 50% of heart failure patients who took treadmill exercise testing. The wearable Holter-accelerometer recording could help to identify impaired chronotropic response to physical activities in heart failure patients.Trial registrationClinicalTrials.gov ID NCT02358603. Registered 16 May 2014.

The Fontan Operation is Not the End of the Road.

The purpose of essay is to increase the awareness on what patients, families and those involved in the treatment and follow-up can face in the long run regarding the survivors of the Fontan operation (FO) and to provide some clues to diminish the deleterious effects of the single ventricle (SV) physiology. Although a significant number of patients survive and are initially asymptomatic, most probably due to adaptation to their limitations, an active approach without being pessimistic is needed in order to prevent problems and thereby improve the long-term prognosis of these patients. When William Harvey described the circulation he stated: Those who believe that one ventricle can drive blood full of spirit into the body and the lungs likewise, are heretics. They forget that nature, being divine, never gave a heart to any where there was no need. When Fontan and Baudet published their procedure they advised us that this procedure is not an anatomical correction, which would require the creation of a right ventricle, but a way of physiological pulmonary blood flow restoration, with suppression of right and left blood flow mixing.1 They also described the Ten commandments, a list of precise recommendations regarding the indications for surgery.2 Some of the problems that we see today are the result of not following their guidelines. Although they clearly defined the main purpose of procedure, they could not anticipate the long-term implications of improvement. More than forty years later, we are witnessing the consequences of not having a sub-pulmonary ventricle. Although clinical experience shows that to survive we do not need a pumping chamber to drive blood into the lungs, the non-pulsatile flow of both vena cava directly connected to the pulmonary circulation results in the following unintended consequences: 1) elevated central venous pressure, and 2) suboptimal cardiac output, relative to the normal two-ventricle state due to: a) impaired chronotropic response to exercise; b) decreased capability to transport a normal blood volume across the pulmonary vascular bed, resulting in reduced ventricular filling and low stroke volume; c) inability to adequately increase stroke volume during periods of increased demand; and, d) elevated systemic vascular resistance with deprived tissue perfusion and anaerobic metabolism.

Abstract 15692: Resting Heart Rate and Chronotropic Response to Exercise: Prognostic Implications in Heart Failure

Background: Higher resting heart rate (HR) and impaired chronotropic response to exercise are both prognostic of adverse outcomes in heart failure (HF). We aimed to study how resting HR and chronotropic response to exercise relate to each other, and to examine their prognostic value in HF patients across the LVEF spectrum. Methods: We studied 892 HF outpatients (mean age 55 years, 68% male, 33% with atrial fibrillation) who underwent maximal cardiopulmonary exercise testing. Chronotropic index (CIx) was calculated as (peak HR – resting HR)/(age-predicted maximal HR – resting HR). Cox proportional hazards models were fit to study the relationship between CIx and resting HR with the composite outcome of LVAD implantation, transplantation, or death (243 events during 4.2±1.9 yr of follow-up). Multivariate models adjusted for age, sex, symptomatic status, cardiomyopathy etiology, COPD, diabetes, atrial fibrillation, LVEF, eGFR, beta-blocker use, and peak VO 2 . Results: Resting HR was 72±14 bpm and CIx was 0.55±0.28. The average LVEF was 33±15%, with 28% with an LVEF ≥45%. 85% of patients were on beta-blockers. Both higher resting HR and lower CIx were associated with higher NYHA class and lower peak VO 2 , but resting HR poorly correlated with CIx (r=0.07; p=0.04). Both higher resting HR (per SD change: adjusted HR 1.26; 95%CI: 1.09-1.46; p=0.002) and CIx (per SD change: adjusted HR 0.63; 95%CI: 0.63-0.89; p=0.001) were independent prognostic markers in adjusted analyses including both measures. Similar findings were noted in analyses restricted to patients with an LVEF ≥45% or with atrial fibrillation. Conclusion: Higher resting HR and lower CIx are both associated with more severe HF, but correlate poorly with each other. Both are predictive of adverse outcomes suggesting that these two HR-related measures provide independent prognostic information.

Central cardiac limit to aerobic capacity in patients with exertional pulmonary venous hypertension: implications for heart failure with preserved ejection fraction.

The mechanism of functional limitation in heart failure with preserved ejection fraction remains controversial. We examined the contributions of central cardiac and peripheral mechanisms and hypothesized that the pulmonary vascular response to exercise is an important determinant of aerobic capacity among patients with exertional pulmonary venous hypertension (ePVH). We compared 31 ePVH patients (peak VO2<80% of predicted and peak pulmonary arterial wedge pressure≥20 mm Hg) with 31 age- and sex-matched controls (peak VO2>80% predicted) who underwent invasive cardiopulmonary exercise testing for unexplained exertional intolerance. ePVH patients had lower peak cardiac output (73±14% versus 103±18% predicted; P<0.001) compared with controls, related both to impaired chronotropic response (peak heart rate 111±25 beats per minute versus 136±24 beats per minute; P<0.001) and to reduced peak stroke volume index (47±10 mL/min per m(2) versus 54±15 mL/min per m(2); P=0.03). Peak systemic O2 extraction was not different between groups (arterial-mixed venous oxygen content difference: 13.0±2.1 mL/dL versus 13.4±2.4 mL/dL; P=0.46). ePVH patients had higher resting (150±74 versus 106±50 dyne/s per cm(-5); P=0.009), peak (124±74 dyne/s per cm(-5) versus 70±41 dyne/s per cm(-5); P<0.001), and isoflow pulmonary vascular resistance (124±74 dyne/s per cm(-5) versus 91±33 dyne/s per cm(-5) at cardiac output≈10.6 L/min; P=0.04). Pulmonary vascular resistance decreased with exercise in all control subjects but increased in 36% (n=11) of ePVH patients. Abnormal pulmonary vascular response was not associated with peak VO2. Reduced cardiac output response, rather than impaired peripheral O2 extraction, constrains oxygen delivery and aerobic capacity in ePVH. Pulmonary vascular dysfunction is common in patients with ePVH at rest and during exercise.

Echocardiographic predictors of chronotropic incompetence to exercise in patients with heart failure with preserved ejection fraction.

Exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) is most often attributed to diastolic dysfunction (DD); however, chronotropic incompetence (CI) could also play an important role. We intended to examine whether there are predictive echocardiographic parameters of DD for impaired chronotropic response to exercise. Patients (n = 143) with unexplained dyspnea and/or exercise intolerance who fulfilled clinical and echocardiographic criteria of HFpEF presence underwent a symptom-limited exercise test using a treadmill (ETT) according to the Bruce protocol. CI was defined as an achieved heart rate reserve (HRR) of ≤ 80%. Comparison of the groups with (n = 98) and without CI (n = 45) did not show any statistically significant difference regarding demographic and clinical characterristics except for use of beta blockers (BB) that were more frequently present (p = 0.012) in patients with CI in comparison with those without. Patients with CI had a higher mean E-wave velocity, E/A ratio, increased E/E' septal, lateral as well as average ratio and abnormal IVRT/TE-e' index all consistent with elevated LV filling pressures. E/E' average ratio > 15 was statistically insignificantly more frequently present in patients with CI. In addition, by multivariate stepwise regression analysis value of E' septal (β = 3.697, 95%CI 0.921-6.473, p = 0.009) along with use of BB, current smoking and basal heart rate appeared as statistically significant independent predictors of lower HRR %. Patients with HFpEF frequently have chronotropic incompetence to graded exercise which may partly be predicted with echocardiographic parameters that are consistent with elevated LV filling pressures.

Heart rate recovery in asymptomatic patients with Chagas disease.

BackgroundChagas disease patients with right bundle-branch block (RBBB) have diverse clinical presentation and prognosis, depending on left ventricular (LV) function. Autonomic disorder can be an early marker of heart involvement. The heart rate recovery (HRR) after exercise may identify autonomic dysfunction, with impact on therapeutic strategies. This study was designed to assess the HRR after symptom-limited exercise testing in asymptomatic Chagas disease patients with RBBB without ventricular dysfunction compared to patients with indeterminate form of Chagas disease and healthy controls.MethodsOne hundred and forty-nine subjects divided into 3 groups were included. A control group was comprised of healthy individuals; group 1 included patients in the indeterminate form of Chagas disease; and group 2 included patients with complete RBBB with or without left anterior hemiblock, and normal ventricular systolic function. A symptom-limited exercise test was performed and heart rate (HR) response to exercise was assessed. HRR was defined as the difference between HR at peak exercise and 1 min following test termination.ResultsThere were no differences in heart-rate profile during exercise between healthy individuals and patients in indeterminate form, whereas patients with RBBB had more prevalence of chronotropic incompetence, lower exercise capacity and lower HRR compared with patients in indeterminate form and controls. A delayed decrease in the HR after exercise was found in 17 patients (15%), 9% in indeterminate form and 24% with RBBB, associated with older age, worse functional capacity, impaired chronotropic response, and ventricular arrhythmias during both exercise and recovery. By multivariable analysis, the independent predictors of a delayed decrease in the HRR were age (odds ratio [OR] 1.11; 95% confidence interval [CI] 1.03 to 1.21; p = 0.010) and presence of RBBB (OR 3.97; 95% CI 1.05 to 15.01; p = 0.042).ConclusionsA small proportion (15%) of asymptomatic Chagas patients had attenuated HRR after exercise, being more prevalent in patients with RBBB compared with patients in indeterminate form and controls.

Prognostic significance of impaired chronotropic response to pharmacologic stress Rb-82 PET

BackgroundAn impaired chronotropic response to exercise is an accepted risk marker but the relationship between heart rate reserve (HRR) with pharmacologic stress is less well-established. The primary aim of this analysis was to evaluate the prognostic significance of HRR in patients undergoing rest/stress myocardial perfusion positron emission tomography (PET) in estimating coronary artery disease (CAD) mortality. MethodsThis subset analysis from the PET Prognosis Multicenter Registry includes a total of 2,398 patients undergoing rest/stress Rb-PET from three participating sites. The HRR from rest to peak stress was categorized into tertiles of ≤4, 5-14, and ≥15 beats per minute (bpm). At stress, the % abnormal myocardium was categorized as <5 %, 5-9.9 %, and ≥10 %. We estimated CAD mortality using univariable and multivariable Cox proportional hazard models. ResultsCAD mortality was 12.8 %, 3.4 %, and 0.8 %, respectively, for HRR measurements of ≤4, 5-14, and ≥15 bpm (P < 0.0001). In a multivariable model, the HRR was independently predictive of CAD mortality (P < 0.0001) with adjusted hazard ratios elevated 3.5- and 8.4-fold for HRR of 5-14 and ≤4 versus ≥15 bpm. In a multivariable model, both the HRR and stress MPI % abnormal myocardium were independently and highly predictive of CAD mortality. Moreover, the net reclassification improvement was 0.18 for the HRR when compared to a model including risk factors, symptoms, rest HR, and PET variables (P = 0.0008). For those with ≥10 % abnormal myocardium on stress PET, there was a graded relationship between HRR and CAD mortality with adjusted hazards exceeding 50-fold for measurements of 5-14 and ≤4 bpm (P < 0.0001) compared to stress MPI with <5 % abnormal myocardium and a HRR ≥15 bpm. ConclusionA diminished HRR to vasodilator stress is a novel but increasingly important predictor of CAD mortality. HRR measurements of ≤4, 5-14, and ≥15 bpm were independently predictive of CAD mortality and underscore the importance of optimizing readily available novel markers of risk as highly relevant to identifying high and low risk patient subsets.

Circulation: Heart Failure Editors’ Picks

Summary : Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium is a novel drug that breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. In this study, the authors prescribed alagebrium (200 mg daily) or placebo combined with aerobic exercise training or contact control in healthy, sedentary older individuals for 1 year. The authors evaluated overall cardiac function by the use of several modalities, including invasive pressure–volume measurements, exercise testing, and cardiac MRI before and after the training. To the authors’ knowledge, this is the first study to evaluate the effects of alagebrium and exercise training in healthy aged humans. After intervention, exercise training significantly increased exercise capacity, LV mass, and LV end-diastolic volume. Conversely, alagebrium had little effect on exercise capacity or LV geometry. However, alagebrium showed a modest improvement in LV stiffness compared with placebo. This favorable effect of alagebrium on LV stiffness was most prominent in individuals with combined alagebrium and exercise training. Conclusions : Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.1 Summary : Maximum oxygen consumption (peak VO2) and efficiency of ventilation (VE) during exercise (VE/VCO2 slope) are known to stratify adults in heart failure for 1-year survival. On the basis of adult data, a recent American Heart Association scientific statement suggested that peak VO2<50% predicted for age and sex should be considered substantial impairment in exercise performance in children with heart disease and therefore a class I indication for heart transplant listing. This single-center study examined the association of …

Circulation Editors’ Picks

<i>Circulation</i> Editors’ Picks

Impaired chronotropic response to 6-min walk test and reduced survival in interstitial lung disease

Reduced chronotropic response to maximal exercise has been associated with poor survival in people without respiratory disease. The contribution of chronotropic response to exercise limitation and survival in interstitial lung disease (ILD) is not well defined. This study investigated the relationships between chronotropic response during 6-min walk test, exercise capacity and survival in ILD. Eligible participants had ILD, were ambulant and free of heart failure and beta blocker therapy. Chronotropic response during the 6-min walk test was defined as peak heart rate (HR) minus resting HR. Survival was recorded at four years. Sixty-two participants (40 idiopathic pulmonary fibrosis) were included, with mean (SD) TLCO 50(18)% predicted and 6-min walk distance (6MWD) 377 (127) metres. A smaller chronotropic response was associated with reduced 6MWD (r=0.65, p<0.001). Independent predictors of 6MWD were chronotropic response, peak oxygen uptake on cardiopulmonary exercise test; right ventricular systolic pressure on echocardiogram; and age. This model explained 83% of the variance in 6MWD, with 24% of the variance attributable to chronotropic response. A chronotropic response during 6-min walk test of less than 20 beats per minute was an independent predictor of death at four years (odds ratio 10.71, 95% confidence interval 2.67-42.94) in a model that also included oxygen desaturation and forced vital capacity. Impaired chronotropic response to 6-min walk test is associated with reduced 6MWD and reduced survival in ILD, independent of physical fitness and pulmonary hypertension. Investigation of the mechanisms underlying attenuated HR response to exercise in ILD is warranted.

Circulation Editors’ Picks

<i>Circulation</i> Editors’ Picks

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Heart Rate Response to a Timed Walk and Cardiovascular Outcomes in Older Adults: The Cardiovascular Health Study

Objectives: To determine the relationship between heart rate response during low-grade physical exertion (6-min walk) with mortality and adverse cardiovascular outcomes in the elderly. Methods: Participants in the Cardiovascular Health Study who completed a 6-min walk test were included. We used delta heart rate (difference between postwalk heart rate and resting heart rate) as a measure of chronotropic response and examined its association with (1) all-cause mortality and (2) incident coronary heart disease event, using multivariable Cox regression models. Results: We included 2,224 participants (mean age 77 ± 4 years; 60% women; 85% white). The average delta heart rate was 26 beats/min. Participants in the lowest tertile of delta heart rate (<20 beats/min) had higher risk-adjusted mortality [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00–1.40] and incident coronary heart disease (HR 1.37, 95% CI 1.05–1.78) compared to subjects in the highest tertile (≥30 beats/min), with a significant linear trend across tertiles (p for trend <0.05 for both outcomes). This relationship was not significant after adjustment for distance walked. Conclusion: Impaired chronotropic response during a 6-min walk test was associated with an increased risk of mortality and incident coronary heart disease among the elderly. This association was attenuated after adjusting for distance walked.

Paradoxical Effect of Increased Diastolic Ca 2+ Release and Decreased Sinoatrial Node Activity in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia is characterized by stress-triggered syncope and sudden death. Patients with catecholaminergic polymorphic ventricular tachycardia manifest sinoatrial node (SAN) dysfunction, the mechanisms of which remain unexplored. We investigated SAN [Ca(2+)](i) handling in mice carrying the catecholaminergic polymorphic ventricular tachycardia-linked mutation of ryanodine receptor (RyR2(R4496C)) and their wild-type (WT) littermates. In vivo telemetric recordings showed impaired SAN automaticity in RyR2(R4496C) mice after isoproterenol injection, analogous to what was observed in catecholaminergic polymorphic ventricular tachycardia patients after exercise. Pacemaker activity was explored by measuring spontaneous [Ca(2+)](i) transients in SAN cells within the intact SAN by confocal microscopy. RyR2(R4496C) SAN presented significantly slower pacemaker activity and impaired chronotropic response under β-adrenergic stimulation, accompanied by the appearance of pauses (in spontaneous [Ca(2+)](i) transients and action potentials) in 75% of the cases. Ca(2+) spark frequency was increased by 2-fold in RyR2(R4496C) SAN. Whole-cell patch-clamp experiments performed on isolated RyR2(R4496C) SAN cells showed that L-type Ca(2+) current (I(Ca,L)) density was reduced by ≈50%, an effect blunted by internal Ca(2+) buffering. Isoproterenol dramatically increased the frequency of Ca(2+) sparks and waves by ≈5 and ≈10-fold, respectively. Interestingly, the sarcoplasmic reticulum Ca(2+) content was significantly reduced in RyR2(R4496C) SAN cells in the presence of isoproterenol, which may contribute to stopping the "Ca(2+) clock" rhythm generation, originating SAN pauses. The increased activity of RyR2(R4496C) in SAN leads to an unanticipated decrease in SAN automaticity by a Ca(2+)-dependent decrease of I(Ca,L) and sarcoplasmic reticulum Ca(2+) depletion during diastole, identifying subcellular pathophysiological alterations contributing to the SAN dysfunction in catecholaminergic polymorphic ventricular tachycardia patients.

RyR2(R 4496C) Expression Induces Sinoatrial Node Dysfunction

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is an arrhythmogenic disease characterized by stress-triggered syncope and sudden death. While ventricular tachycardia appears only during stress conditions, CPVT patients manifest basal sino-atrial node (SAN) dysfunction, but the underlying mechanism remains unknown. We investigated Ca2+ handling on SAN from transgenic mice expressing the CPVT ryanodine receptor R4496C mutation (RyR2R4496C) and on their wild type (WT) littermates. A 2-fold increase of Ca2+ spark frequency in RyRR4496C SAN cells was recorded in basal conditions during the diastolic periods. beta-adrenergic stimulation with 20 nM isoproterenol, multiplied by ∼10-fold the occurrence of Ca2+ sparks and Ca2+ waves. Spontaneous [Ca2+]i transients recorded by confocal microscope in isolated SAN from RyR2R4496C mice presented a slower beating rate than WT SAN and an impaired positive chronotropic response to beta-adrenergic stimulation. Moreover, isoproterenol induced the appearance of [Ca2+]i transients and action potentials pauses in 75% of RyR2R4496C SAN cells. Caffeine experiments showed that the sarcoplasmic reticulum (SR) Ca2+ load was significantly reduced in the RyR2R4496C SAN cells. In vivo telemetric recordings of electrocardiograms (ECG) identified atrial and junctional escape beats overcoming sinus pauses in RyR2R4496C mice following isoproterenol injection consistent with the pauses recorded in isolated SAN. Similar ECGs were observed in CPVT patients during exercise testing, validating the animal model. We conclude that the increased activity of the RyR2R4496C SAN cells during diastolic periods unloads the SR with Ca2+, participating in SAN dysfunction in CPVT.

Effect of Beta-Blocker Therapy on Rehospitalization Rates in Women Versus Men With Heart Failure and Preserved Ejection Fraction

Beta blockers are empirically used in many patients with heart failure (HF) and preserved ejection fraction (HFpEF) because they allow more time for diastolic filling and because they improve outcomes in patients with systolic HF. However, recent data suggest that impaired chronotropic and vasodilator responses to exercise, which can worsen with beta blockade, may play a key role in the pathophysiology of HFpEF. We prospectively examined the association between beta-blocker therapy after hospitalization for decompensated HF and HF rehospitalization at 6 months in 66 consecutive patients with HFpEF (71 +/- 13 years old, 68% women, 42% Black). Subjects were stratified based on receiving (BB+; 15 men, 28 women) or not receiving (BB-) beta-blockers at hospital discharge. In men, HF rehospitalization occurred less frequently in the BB+ than in the BB- group, albeit nonsignificantly (20% vs 50%, p = 0.29). In women, HF rehospitalization occurred more frequently in the BB+ than in the BB- group (75% vs 18%, p <0.001). In univariate analyses, discharge beta-blocker was associated with HF rehospitalization in women (odds ratio [OR] 14.00, 95% confidence interval [CI] 3.09 to 63.51, p = 0.001), but not in men (OR 0.25, 95% CI 0.03 to 1.92, p = 0.18). In a forward logistic regression model that offered all univariate predictors of HF rehospitalization, discharge beta blocker remained an independent predictor of HF rehospitalization in women (OR 11.06, 95% CI 1.98 to 61.67, p = 0.006). In conclusion, this small observational study suggests that beta-blocker therapy may be associated with a higher risk of HF rehospitalization in women with HFpEF. The risks and benefits of beta-blocker therapy in patients with HFpEF should be evaluated in randomized, controlled trials.

Impaired chronotropic response to exercise in children with repaired cyanotic congenital heart disease

Objective — Conventionally the heart rate response to exercise has been considered as a useful parameter for the assessment of exercise performance. However, in patients with surgical repair of congenital heart defects sino-atrial dysfunction has been observed after cardiac surgery.The purpose of this study was to assess whether the heart rate response to exercise can be used in the assessment of exercise performance.Methods — Fifty-three patients with surgical repair of congenital heart disease underwent exercise testing.The patients were 19 children with repair of tetralogy of Fallot (TOF), 17 patients with arterial switch operation for transposition of the great arteries and 17 patients with a Fontan circulation for functional univentricular heart. The patients were compared to age-matched control subjects. Exercise capacity was assessed by determination of the maximal oxygen uptake.To account for the effect of age and gender on heart rate response, values in the patients were compared to age-matched control subjects of the same age and gender and were expressed as a Z-score of the normal value.Results — In the 3 groups of patients a lower than normal heart rate response was observed during submaximal and maximal exercise, varying from -1.7 to -4.6 standard deviation scores.This was not associated with normal values for exercise capacity in patients with TOF or Fontan circulation, as should be expected.Conclusion — In patients with surgical repair of congenital heart disease, the use of heart rate response in the assessment of cardiovascular exercise performance may be seriously misleading and should be complemented with measurements of gas exchange.

The Restoration of Chronotropic CompEtence in Heart Failure Patient S with Normal Ejection FracTion (RESET) Study: Rationale and Design

Background Heart failure with preserved ejection fraction (HFpEF) is the predominant form of heart failure among the elderly and in women. However, there are few if any evidence-based therapeutic options for HFpEF. The chief complaint of HFpEF is reduced tolerance to physical exertion. Recent data revealed that 1 potential mechanism of exertional intolerance in HFpEF patients is inadequate chronotropic response. Although there is considerable evidence demonstrating the benefits of rate-adaptive pacing (RAP) provided from implantable cardiac devices in patients with an impaired chronotropic response, the effect of RAP in HFpEF is unknown. Methods and Results The Restoration of Chronotropic CompEtence in Heart Failure Patient S with Normal Ejection FracTion (RESET) study is a prospective, multicenter, double-blind, randomized with stratification, study assessing the effect of RAP on peak oxygen consumption and quality of life. RAP therapy will be evaluated in a crossover paired fashion for each patient within each study stratum. Study strata are based on patient β-blocker usage at time of enrollment. The study is powered to assess the impact of pacing independently in both strata. Conclusions The RESET study seeks to evaluate the potential benefit of RAP in patients with symptomatic mild to moderate HFpEF and chronotropic impairment. Study enrollment began in July 2008.

ß-Blocker Therapy Is Associated with Increased Re-Hospitalization for Heart Failure in Women with Heart Failure and Preserved Ejection Fraction

Background: β-blockers are empirically used in many patients with heart failure (HF) and preserved ejection fraction (HFpEF) because they allow more time for diastolic filling and because they improve outcomes in patients with systolic HF. However, recent data suggest that impaired chronotropic and vasodilator responses to exercise, which can worsen with β-blockade, may play a key role in the pathophysiology of HFpEF. Methods and Results: We prospectively examined the association between β-blocker therapy after hospitalization for decompensated HF and HF re-hospitalization at 6 months in 66 consecutive HFpEF patients (Framingham criteria for HF and EF ≥50%).