Clinical Implications for Exercise at Altitude Among Individuals With Cardiovascular Disease: A Scientific Statement From the American Heart Association.

An increasing number of individuals travel to mountainous environments for work and pleasure. However, oxygen availability declines at altitude, and hypoxic environments place unique stressors on the cardiovascular system. These stressors may be exacerbated by exercise at altitude, because exercise increases oxygen demand in an environment that is already relatively oxygen deplete compared with sea-level conditions. Furthermore, the prevalence of cardiovascular disease, as well as diseases such as hypertension, heart failure, and lung disease, is high among individuals living in the United States. As such, patients who are at risk of or who have established cardiovascular disease may be at an increased risk of adverse events when sojourning to these mountainous locations. However, these risks may be minimized by appropriate pretravel assessments and planning through shared decision-making between patients and their managing clinicians. This American Heart Association scientific statement provides a concise, yet comprehensive overview of the physiologic responses to exercise in hypoxic locations, as well as important considerations for minimizing the risk of adverse cardiovascular events during mountainous excursions.

Cardiac Rehabilitation for Patients With Heart Failure: JACC Expert Panel.

Cardiac rehabilitation is defined as a multidisciplinary program that includes exercise training, cardiac risk factor modification, psychosocial assessment, and outcomes assessment. Exercise training and other components of cardiac rehabilitation (CR) are safe and beneficial and result in significant improvements in quality of life, functional capacity, exercise performance, and heart failure (HF)-related hospitalizations in patients with HF. Despite outcome benefits, cost-effectiveness, and strong practice guideline recommendations, CR remains underused. Clinicians, health care leaders, and payers should prioritize incorporating CR as part of the standard of care for patients with HF.

Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation. METHODS: Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30o and 60o. Heart rate and BP were monitored during cardiopulmonary exercise testing. RESULTS: Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing. CONCLUSIONS: Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.

Right ventricular function and cardiopulmonary performance among patients with heart failure supported by durable mechanical circulatory support devices.

BACKGROUND: Patients with continuous-flow left ventricular assist devices (CF-LVADs) experience limitations in functional capacity and frequently, right ventricular (RV) dysfunction. We sought to characterize RV function in the context of global cardiopulmonary performance during exercise in this population. METHODS: A total of 26 patients with CF-LVAD (aged 58 ± 11 years, 23 males) completed a hemodynamic assessment with either conductance catheters (Group 1, n = 13) inserted into the right ventricle to generate RV pressure‒volume loops or traditional Swan‒Ganz catheters (Group 2, n = 13) during invasive cardiopulmonary exercise testing. Hemodynamics were collected at rest, 2 sub-maximal levels of exercise, and peak effort. Breath-by-breath gas exchange parameters were collected by indirect calorimetry. Group 1 participants also completed an invasive ramp test during supine rest to determine the impact of varying levels of CF-LVAD support on RV function. RESULTS: In Group 1, pump speed modulations minimally influenced RV function. During upright exercise, there were modest increases in RV contractility during sub-maximal exercise, but there were no appreciable increases at peak effort. Ventricular‒arterial coupling was preserved throughout the exercise. In Group 2, there were large increases in pulmonary arterial, left-sided filling, and right-sided filling pressures during sub-maximal and peak exercises. Among all participants, the cardiac output‒oxygen uptake relationship was preserved at 5.8:1. Ventilatory efficiency was severely abnormal at 42.3 ± 11.6. CONCLUSIONS: Patients with CF-LVAD suffer from limited RV contractile reserve; marked elevations in pulmonary, left-sided filling, and right-sided filling pressures during exercise; and severe ventilatory inefficiency. These findings explain mechanisms for persistent reductions in functional capacity in this patient population.

Cryptococcal pericarditis in a heart transplant recipient.

We present a case of Cryptococcus neoformans pericarditis in a cardiac transplant recipient. This article reviews the diagnosis, treatment, and complications of cryptococcosis specifically in transplant patients. While pericarditis is a rare manifestation of Cryptococcus infection, this case highlights that cryptococcosis should be considered in the differential diagnosis for solid organ transplant and immunocompromised patients presenting with pericardial effusions.

New insights into resting and exertional right ventricular performance in the healthy heart through real-time pressure-volume analysis.

KEY POINTS: Despite growing interest in right ventricular form and function in diseased states, there is a paucity of data regarding characteristics of right ventricular function - namely contractile and lusitropic reserve, as well as ventricular-arterial coupling, in the healthy heart during rest, as well as submaximal and peak exercise. Pressure-volume analysis of the right ventricle, during invasive cardiopulmonary exercise testing, demonstrates that that the right heart has enormous contractile reserve, with a three- or fourfold increase in all metrics of contractility, as well as myocardial energy production and utilization. The healthy right ventricle also demonstrates marked augmentation in lusitropy, indicating that diastolic filling of the right heart is not passive. Rather, the right ventricle actively contributes to venous return during exercise, along with the muscle pump. Ventricular-arterial coupling is preserved during submaximal and peak exercise in the healthy heart. ABSTRACT: Knowledge of right ventricular (RV) function has lagged behind that of the left ventricle and historically, the RV has even been referred to as a 'passive conduit' of lesser importance than its left-sided counterpart. Pressure-volume (PV) analysis is the gold standard metric of assessing ventricular performance. We recruited nine healthy sedentary individuals free of any cardiopulmonary disease (42 ± 12 years, 78 ± 11 kg), who completed invasive cardiopulmonary exercise testing during upright ergometry, while using conductance catheters inserted into the RV to generate real-time PV loops. Data were obtained at rest, two submaximal levels of exercise below ventilatory threshold, to simulate real-world scenarios/activities of daily living, and maximal effort. Breath-by-breath oxygen uptake was determined by indirect calorimetry. During submaximal and peak exercise, there were significant increases in all metrics of systolic function by three- to fourfold, including cardiac output, preload recruitable stroke work, and maximum rate of pressure change in the ventricle (dP/dtmax ), as well as energy utilization as determined by stroke work and pressure-volume area. Similarly, the RV demonstrated a significant, threefold increase in lusitropic reserve throughout exercise. Ventricular-arterial coupling, defined by the quotient of end-systolic elastance and effective arterial elastance, was preserved throughout all stages of exercise. Maximal pressures increased significantly during exercise, while end-diastolic volumes were essentially unchanged. Overall, these findings demonstrate that the healthy RV is not merely a passive conduit, but actively participates in cardiopulmonary performance during exercise by accessing an enormous amount of contractile and lusitropic reserve, ensuring that VA coupling is preserved throughout all stages of exercise.

Relationship between nocturnal blood pressure patterns and end organ damage and diastolic dysfunction in heart transplant recipients.

BACKGROUND: We assessed the relationship between circadian blood pressure (BP) patterns and clinical outcomes in a contemporary cohort of adult heart transplant recipients. METHODS: This retrospective, cross-sectional study included adult heart transplant recipients at least 6 months post-transplant. Ambulatory BP measurements were recorded over 24 hours. Nondippers were defined as a decline in average nighttime BP ≤ 10% compared with daytime. Primary outcomes were the presence of end organ damage, that is, microalbuminuria, chronic kidney disease, and/or left ventricular hypertrophy. Secondary outcomes were measures of diastolic dysfunction (ie, mitral valve deceleration time, e/e', E/A, and isovolumetric relaxation time), microalbumin/creatinine ratio, eGFR, interventricular septal thickness, and left ventricular posterior wall thickness. RESULTS: Of 30 patients, 53.3% (n = 16) were systolic nondippers and 40% (n = 12) were diastolic nondippers. Diastolic nondippers had three times higher urine microalbumin/creatinine ratios than diastolic dippers (P = .03). Systolic nondippers had 16.3% lower mitral valve deceleration time (P = .05) than systolic dippers, while diastolic nondippers had 20.4% higher e/e' (P = .05) than diastolic dippers. There were no significant relationships between BP dipping status and any of the primary outcomes. CONCLUSIONS: These data suggest that systolic and diastolic nondipping BP patterns are associated with subclinical kidney damage and diastolic dysfunction in heart transplant recipients.

Will the Early Use of Biomarkers Prevent the Development of Heart Failure?

Alterations in biomarkers are associated with the development and progression of heart failure. As indicated by the study of Ergatoudes and colleagues in the current issue of this journal, biomarkers may also be the first sign of increased risk of developing heart failure. Prior studies also suggest that elevations in certain biomarkers can lead to more frequent clinical surveillance and initiation of therapeutic strategies that may prevent or delay the development of heart failure.

A Case of Cough-induced Ventricular Tachycardia in a Patient with a Left Ventricular Assist Device.

In this case, the patient's ventricular tachycardia (VT) was specifically induced by coughing, which has not previously been described. Decreasing the rotational speed of the left ventricular assist device (LVAD) and increasing preload by stopping the patient's nitrates and reducing diuretic dose allowed improved filling of the left ventricle (LV) and increased LV volumes. When coughing recurred, the effects on the LV cavity were less pronounced and thus VT was reduced. Although ventricular arrhythmias are common after LVAD placement, this is a unique case in which VT was caused by coughing, which is ordinarily not considered arrhythmogenic.

Sex differences in the effects of type 2 diabetes on exercise performance.

PURPOSE: People with uncomplicated type 2 diabetes (T2D) have impaired peak exercise performance compared with that of their nondiabetic counterparts. This impairment may represent the earliest indication of cardiovascular (CV) abnormalities in T2D. Women with T2D are known to have worse CV outcomes than those in men with T2D. We hypothesized that women with diabetes have a greater exercise impairment than that in men with diabetes compared with that in their nondiabetic counterparts. METHODS: We studied 15 women (premenopausal) and 14 men with T2D as well as their nondiabetic counterparts (22 women and 13 men). Exercise testing was performed. Additional outcomes included measurements of insulin sensitivity, endothelial function, blood flow, and resting cardiac function. RESULTS: Men and women with T2D but not controls had impaired insulin sensitivity. Women with T2D had a lower peak oxygen consumption (V˙O2peak) compared with that of nondiabetic women (24%, P < 0.05) than men with diabetes compared with that in nondiabetic men (16%, P < 0.05) (P value between groups < 0.05). The time constants (phase 2) of the V˙O2 kinetic response tended to be slower in men and women with T2D than those in nondiabetic controls (P = 0.08). There were no differences in resting ventricular function by Doppler echocardiography techniques between groups. Women with T2D had significantly lower flow-mediated dilation and blood flow responses to hyperemia than those in nondiabetic women (both P < 0.05), whereas men with T2D had lower flow-mediated dilation but not lower blood flow than those in nondiabetic men. CONCLUSIONS: Although both men and women with uncomplicated T2D had a lower V˙O2peak, the abnormality in women with T2D compared with that in nondiabetic women was greater than that seen in men. Because V˙O2peak has a strong inverse correlation with mortality, sex disparities observed in exercise capacity among people with T2D suggest a possible rationale for the increased CV morbidity and mortality observed in women compared with those observed in men with uncomplicated T2D.

Comparison of office, home, and ambulatory blood pressure in heart transplant recipients.

BACKGROUND: The purpose of this study was to prospectively evaluate the relationship between office, home, and ambulatory blood pressure (BP) in heart transplant recipients. METHODS AND RESULTS: The study enrolled 30 adults ≥ 6 months after heart transplantation. Morning seated office BP was measured with the use of an automatic device at 3 outpatient visits. Seated home BP was measured in the morning and evening for 5 consecutive days. Ambulatory BP was measured over 24 hours with the use of a Spacelabs monitor. The strongest correlation was observed between home and 24-hour ambulatory BP (r = 0.79 systolic; r = 0.72 diastolic). Office and home systolic BPs were significantly lower than daytime ambulatory BP (office, -3.7 mm Hg, P = .009; home, -2.6 mm Hg, P = .05). Ambulatory monitoring identified more participants with BP above hypertensive limits than did office or home measurements (63%, 50%, and 13%, respectively; P = .003). Ambulatory monitoring also revealed high BP loads, abnormal nocturnal BP patterns (eg, 30% nondippers), and a high percentage of masked hypertension (37% home, 50% ambulatory). CONCLUSIONS: Office and home BP monitoring are acceptable but may underestimate BP burden in heart transplant recipients. Additional studies are needed to determine which BP method is superior for the management of hypertension and associated outcomes after heart transplantation.

Usefulness of Doppler echocardiographic left ventricular diastolic function and peak exercise oxygen consumption to predict cardiovascular outcomes in patients with systolic heart failure (from HF-ACTION).

Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) was a multicenter, randomized controlled trial designed to examine the safety and efficacy of aerobic exercise training versus usual care in 2,331 patients with systolic heart failure (HF). In HF-ACTION patients with rest transthoracic echocardiographic measurements, the predictive value of 8 Doppler echocardiographic measurements-left ventricular (LV) diastolic dimension, mass, systolic (ejection fraction) and diastolic (mitral valve peak early diastolic/peak late diastolic [E/A] ratio, peak mitral valve early diastolic velocity/tissue Doppler peak early diastolic myocardial velocity [E/E'] ratio, and deceleration time) function, left atrial dimension, and mitral regurgitation severity-was examined for a primary end point of all-cause death or hospitalization and a secondary end point of cardiovascular disease death or HF hospitalization. Also compared was the prognostic value of echocardiographic variables versus peak oxygen consumption (Vo(2)). Mitral valve E/A and E/E' ratios were more powerful independent predictors of clinical end points than the LV ejection fraction but less powerful than peak Vo(2). In multivariate analyses for predicting the primary end point, adding E/A ratio to a basic demographic and clinical model increased the C-index from 0.61 to 0.62, compared with 0.64 after adding peak Vo(2). For the secondary end point, 6 echocardiographic variables, but not the LV ejection fraction or left atrial dimension, provided independent predictive power over the basic model. The addition of E/E' or E/A to the basic model increased the C-index from 0.70 to 0.72 and 0.73, respectively (all p values <0.0001). Simultaneously adding E/A ratio and peak Vo(2) to the basic model increased the C-index to 0.75 (p <0.0005). No echocardiographic variable was significantly related to the change from baseline to 3 months in exercise peak Vo(2). In conclusion, the addition of echocardiographic LV diastolic function variables improves the prognostic value of a basic demographic and clinical model for cardiovascular disease outcomes.

Relationship of Doppler-Echocardiographic left ventricular diastolic function to exercise performance in systolic heart failure: the HF-ACTION study.

INTRODUCTION: Patients with systolic heart failure often have concomitant left ventricular (LV) diastolic dysfunction. Although in animal models diastolic dysfunction is associated with worsening exercise capacity and prognosis, information regarding these relationships in patients with established systolic heart failure (HF) is sparse. METHODS: HF-ACTION was a large, multicenter National Institutes of Health-funded trial of exercise training in systolic HF (LV ejection fraction [LVEF] < or = 35%) and included detailed Doppler-echocardiographic (echo) and cardiopulmonary exercise testing at baseline. We tested the hypothesis that echo measures of LV diastolic function predict key cardiopulmonary exercise outcomes, including aerobic exercise capacity (peak exercise oxygen consumption, VO(2)), distance in the 6-minute walk test (6MWD), and ventilatory efficiency (VE/VCO(2) slope) in patients with systolic HF. RESULTS: Overall, 2,331 patients (28% women, median age 59 years, median LVEF 25%) were enrolled. There were significant bivariate correlations between echo diastolic function variables and peak VO(2) (inverse) and VE/VCO(2) slope (direct) that were strongest for ratio of early diastolic peak transmitral (MV) to myocardial tissue velocity (E/E'), peak MV early-to-late diastolic velocity ratio (E/A), and left atrial dimension (range of absolute r = 0.16-0.28). Both MV E/A and E/E' were more strongly related to all 3 exercise variables than was LVEF. The relationships of E/A and E/E' with 6MWD were weaker than with peak VO(2) or VE/VCO(2) slope. A multivariable model with peak VO(2) as the dependent variable, which included MV E/A and 9 demographic predictors including age, sex, race, body mass index, and New York Heart Association class, explained 40% of the variation in peak VO(2), with MV E/A explaining 6% of the variation. Including LVEF in the model explained less than an additional 1% of the variance in peak VO(2). In a multivariable model for VE/VCO(2) slope, MV E/A was the strongest independent echo predictor, explaining 10% of the variance. The relationship of LV diastolic function variables with 6MWD was weaker than with peak VO(2) or VE/VCO(2) slope. CONCLUSION: In patients with systolic HF, LV early diastolic function is a modest independent predictor of aerobic exercise capacity and appears to be a better predictor than LVEF.

Cardiac dysfunction during exercise in uncomplicated type 2 diabetes.

PURPOSE: Type 2 diabetes mellitus (T2DM) has been associated with reduced peak exercise capacity (VO(2peak)). The causes of this impairment are not clearly established, but evidence suggests that abnormalities in cardiac function play a significant role. We hypothesized that exercise would be associated with impaired cardiac function and hemodynamics in recently diagnosed T2DM, even in the absence of clinically evident cardiovascular complications. METHODS: After baseline normal echocardiography screening, 10 premenopausal women with uncomplicated T2DM (average duration of diagnosed T2DM, 3.6 yr) and 10 healthy nondiabetic women of similar age, weight, and activity levels performed a peak cardiopulmonary exercise test while instrumented with an indwelling pulmonary artery catheter for assessing cardiac function. On separate days, technetium-99m sestamibi (cardolite) imaging was performed to assess myocardial perfusion at rest and peak exercise in seven T2DM and seven control patients. RESULTS: Resting measures of cardiac hemodynamics were similar in T2DM and control subjects. Absolute VO(2peak) (mL x min(-1)) and peak cardiac output (L x min(-1)) tended to be lower in T2DM than in control subjects but did not reach statistical significance. However, pulmonary capillary wedge pressure (PCWP) rose significantly more during exercise in T2DM than in controls (148% vs 109% increase at peak exercise, P < 0.01). Normalized myocardial perfusion index was lower in persons with diabetes than in controls (11.0 +/- 3.5 x e(-9) vs 17.5 +/- 8.1 x e(-9), respectively, P < 0.05) and inversely related to peak exercise PCWP (R = -0.56, P < 0.05). CONCLUSIONS: Cardiac hemodynamics during graded exercise are altered in women with recently diagnosed T2DM as demonstrated by the disproportionate increase in PCWP at peak exercise compared with controls subjects. Cardiac abnormalities observed are potentially early signs of subclinical cardiac dysfunction associated with T2DM, which may precede the more greatly impaired cardiac function at rest and with exercise observed in longer established T2DM.

Myocardial glucose and lactate metabolism during rest and atrial pacing in humans.

There is minimal in vivo data in humans evaluating myocardial substrate utilization during increased heart work. This study was performed to determine the balance of myocardial glucose and lactate metabolism during rest and increased heart work induced by atrial pacing in seven healthy men and women (age, 49.7 +/- 3.9 years; body mass index, 23.4 +/- 1.1 kg m(-2), maximum oxygen consumption, 35.5 +/- 3.0 ml kg(-1) min(-1), ejection fraction, 68 +/- 3%). After 3 days of dietary control, catheters were placed in coronary sinus, femoral arterial and venous, and peripheral venous blood vessels. Subjects received a primed continuous infusion of [3,3,3-(2)H]lactate and [6,6-(2)H]glucose throughout the study. Arterial and coronary sinus blood sampling and measurements of coronary sinus blood flow were made during rest and atrial pacing at approximately 111 beats min(-1). Myocardial oxygen consumption increased (P = 0.04) from rest to atrial pacing. Net glucose uptake increased (P = 0.04) from rest to atrial pacing with unchanged fractional extraction (rest: 9.1 +/- 2.7%, atrial pacing 9.8 +/- 2.9%). The percentage of whole body glucose disposal from myocardial uptake also increased from rest to atrial pacing. Isotopically measured lactate uptake also increased significantly from rest to atrial pacing with no significant differences in fractional extraction. The myocardium released lactate throughout the experiment, which increased significantly from rest and atrial pacing (P < 0.05). The heart accounted for a significantly greater percentage of whole body lactate disposal during atrial pacing (15.0 +/- 4.4%) compared to rest (4.9 +/- 0.9%, P = 0.03). These data suggest: (1) in the absence of ischaemia the myocardium is constantly taking up and releasing lactate at rest which increases during atrial pacing, and (2) when arterial substrate delivery is unchanged, increased myocardial work is accomplished with similar proportions of glucose and lactate utilization in healthy humans in vivo.

Myocardial FFA metabolism during rest and atrial pacing in humans.

There is limited in vivo data in humans evaluating myocardial fat utilization during increased heart work. This study was done to determine myocardial free fatty acid (FFA) metabolism during rest and atrial pacing, which increases cardiac work without changing arterial substrate concentration. We studied seven healthy men and women (age = 49.7 +/- 3.9 yr, BMI = 23.4 +/- 1.1 kg/m(2), Vo(2max) = 35.5 +/- 3.0 ml.kg(-1).min(-1), ejection fraction = 68 +/- 3%). After 3 days of dietary control, coronary sinus, femoral arterial and venous, and peripheral venous catheters were placed. Subjects received [(13)C]bicarbonate followed by a continuous infusion of [1-(13)C]palmitate through the end of the study. Arterial and coronary sinus blood sampling and measurements of resting coronary sinus blood flow were made during rest and atrial pacing to 120 beats/min. MVo(2) increased (P < 0.05) from rest to atrial pacing. Coronary sinus FFA concentration was significantly lower than arterial through rest and atrial pacing (P = 0.007). Isotopically measured myocardial palmitate uptake increased significantly from rest to atrial pacing (P = 0.03). Approximately one-third of palmitate delivery was extracted by the myocardium during rest and atrial pacing. Myocardial V(13)CO(2) production and palmitate oxidation increased significantly from rest (P < 0.01) to atrial pacing. Net glycerol balance was significantly greater than zero during rest (P = 0.04) but not different from zero during atrial pacing (P = 0.13). These data suggest that myocardial lipid uptake and oxidation increase with greater heart work during atrial pacing, with a similar relative proportion of fat oxidation to total myocardial energy expenditure.

Left ventricular assist device as bridge to transplantation does not adversely affect one-year heart transplantation survival.

OBJECTIVE: Left ventricular assist devices are increasingly used as a bridge to transplantation. It remains unclear whether the use of pretransplant left ventricular assist devices adversely affects short-term survival after cardiac transplantation. METHODS: A retrospective review of 317 consecutive patients undergoing cardiac transplantation at an academic center between 1986 and 2006 was undertaken. Left ventricular assist devices were used pretransplant in 23 of these 317 patients, and 294 patients did not require left ventricular assist device support. Patients with a left ventricular assist device were supported with a Heartmate VE or Heartmate XVE (Thoratec Corp, Pleasanton, Calif). Kaplan-Meier survival estimates were compared between the left ventricular assist device group and the non-left ventricular assist device group using the log-rank test. In addition, occurrence of death was analyzed between the 2 groups with a chi-square analysis. The results are expressed as 1-year survival with 95% confidence intervals in parentheses. RESULTS: The 1-year survival for all 317 patients was 0.86 (0.82-0.90). The patient survival for the group without a left ventricular assist device before cardiac transplant was 0.87 (0.83-0.90), and the survival for the group with a left ventricular assist device as bridge to transplantation was 0.83 (0.67-0.98; P = .77). For the deaths that occurred in all 317 patients, 19% of the patients without left ventricular assist devices died within 30 days of transplant, whereas 80% of the patients with left ventricular assist devices died within 30 days of transplant (P < .01). CONCLUSION: When used as a bridge to transplantation, left ventricular assist devices do not compromise 1-year survival after cardiac transplantation. Of the patients who die after transplantation, patients bridged with left ventricular assist devices are at higher risk for death within 30 days of transplant. These data suggest that left ventricular assist devices as a bridge to transplantation should be considered for appropriately selected patients awaiting cardiac transplantation.

Impact of cardiac resynchronization therapy on exercise performance, functional capacity, and quality of life in systolic heart failure with QRS prolongation: COMPANION trial sub-study.

BACKGROUND: A total of 405 participants in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure trial were prospectively enrolled in an exercise sub-study designed to study the influence of cardiac resynchronization therapy (CRT) on measures of exercise capacity, functional capacity, and quality of life (QOL). METHODS AND RESULTS: Substudy eligibility included New York Heart Association (NYHA) functional Class III or IV heart failure, left ventricular ejection fraction < or =0.35, QRS interval of > or =120 ms, normal sinus rhythm, a heart failure hospitalization (or equivalent) within 1 year, a peak VO2 < or =22 mL x kg x min, the ability to walk 150 to 425 meters in 6 minutes, forced expiratory volume in 1 second/forced vital capacity > or =50%, and no clinical indication for a pacemaker or implantable cardioverter-defibrillator. Patients were randomized in a 1:4 ratio to optimal medical therapy (OPT) or to OPT plus CRT. Cardiopulmonary exercise testing (peak VO2 and 6-minute walk distance [6MWD]) and assessment of NYHA functional class and QOL were assessed at baseline and at 3 and 6 months of assigned therapy. There was no significant improvement in peak VO2 at 6 months in the CRT group compared with the OPT group (+0.63 mL x kg x min) by unadjusted analysis (P = .05) or by analyses adjusted for missing data. Thus the primary end point of the study was not met. There was significantly greater improvement in the 6MWD in the CRT group compared with the OPT group at both 3 and 6 months by both statistical methods (P < or = .045). Likewise, a greater proportion of CRT patients improved by 1 or more NYHA functional classes (P < .01) at 3 months and had better QOL scores (P < .01) at 3 and 6 months compared with the OPT patients. Baseline peak VO2 predicted clinical events (time to death, time to death or first hospitalization, or time to death and first heart failure hospitalization: P < .05) in CRT participants. CONCLUSION: CRT patients with moderate to advanced symptoms of systolic heart failure and prolonged QRS intervals benefit from the addition of CRT to OPT in terms of exercise capacity, functional status, and QOL. CRT should be considered standard therapy in this select group of heart failure patients.