Permanent pacemaker insertion after CoreValve transcatheter aortic valve implantation: incidence and contributing factors (the UK CoreValve Collaborative).

BACKGROUND: Permanent pacemaker (PPM) requirement is a recognized complication of transcatheter aortic valve implantation. We assessed the UK incidence of permanent pacing within 30 days of CoreValve implantation and formulated an anatomic and electrophysiological model. METHODS AND RESULTS: Data from 270 patients at 10 centers in the United Kingdom were examined. Twenty-five patients (8%) had preexisting PPMs; 2 patients had incomplete data. The remaining 243 were 81.3±6.7 years of age; 50.6% were male. QRS duration increased from 105±23 to 135±29 milliseconds (P<0.01). Left bundle-branch block incidence was 13% at baseline and 61% after the procedure (P<0.001). Eighty-one patients (33.3%) required a PPM within 30 days. Rates of pacing according to preexisting ECG abnormalities were as follows: right bundle-branch block, 65.2%; left bundle-branch block, 43.75%; normal QRS, 27.6%. Among patients who required PPM implantation, the median time to insertion was 4.0 days (interquartile range, 2.0 to 7.75 days). Multivariable analysis revealed that periprocedural atrioventricular block (odds ratio, 6.29; 95% confidence interval, 3.55 to 11.15), balloon predilatation (odds ratio, 2.68; 95% confidence interval, 2.00 to 3.47), use of the larger (29 mm) CoreValve prosthesis (odds ratio, 2.50; 95% confidence interval, 1.22 to 5.11), interventricular septum diameter (odds ratio, 1.18; 95% confidence interval, 1.10 to 3.06), and prolonged QRS duration (odds ratio, 3.45; 95% confidence interval, 1.61 to 7.40) were independently associated with the need for PPM. CONCLUSION: One third of patients undergoing a CoreValve transcatheter aortic valve implantation procedure require a PPM within 30 days. Periprocedural atrioventricular block, balloon predilatation, use of the larger CoreValve prosthesis, increased interventricular septum diameter and prolonged QRS duration were associated with the need for PPM.

Pneumocystis pneumonia in solid organ transplant recipients: not yet an infection of the past.

BACKGROUND: Solid organ transplant (SOT) recipients are at risk for Pneumocystis pneumonia (PCP), especially in the first year post transplant. Although trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis substantially decreases this risk, there is little data or consensus on optimal duration of prophylaxis. Consequently, there is lack of standardization of prophylaxis duration (3 months to lifelong, depending on organ group) in SOT programs. METHODS: We performed a retrospective chart review of all cases of confirmed PCP, in adult kidney, pancreas, liver, and lung transplant recipients from 2001 to 2011 in our SOT program. RESULTS: Of 1241 patients followed in our clinic (657 kidney, 44 kidney/pancreas, 436 liver, and 104 lung or heart/lung), a total of 14 PCP cases were identified in 2 kidney, 1 kidney/pancreas, 5 liver, 5 single lung, and 1 heart/lung transplant recipient. At the time of PCP diagnosis, immunosuppression in most cases consisted of prednisone, tacrolimus, and mycophenolate mofetil (79% of patients), and 53% had previously received TMP-SMX for prophylaxis. None were on PCP prophylaxis at the time of illness onset. PCP occurred early in all 5 liver transplant recipients and in 1 kidney transplant recipient, none of whom had ever received prophylaxis (17-204 days post transplant). Of those who had received 6 months of prophylaxis (1 kidney, 1 kidney/pancreas), PCP occurred at 846 and 4778 days, respectively. Late onset PCP occurred in lung recipients who had received 12 months of prophylaxis (lung 645-1414 days, heart/lung 1583 days post transplant). Five patients had experienced acute rejection and 6 patients had cytomegalovirus (CMV) viremia on average 59 and 204 days preceding PCP, respectively. Three deaths (1 liver, 2 lung) were thought to be directly related to complications of PCP. CONCLUSION: Our experience with late PCP cases in lung transplant recipients receiving only 1 year of prophylaxis lends support to prolonged PCP prophylaxis in this group. Given the number of patients who had experienced an acute rejection episode or CMV disease preceding PCP in non-lung SOT recipients, consideration should be given to re-institution of PCP prophylaxis for a period of time after these events in kidney, kidney/pancreas, and liver transplant recipients.

Candidate genes for COPD in two large data sets.

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV1 % predicted and FEV1/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

Introduction of spirometry into clinical practice in Georgetown, Guyana: quality and diagnostic outcomes.

SETTING: Georgetown Public Hospital Corporation (GPHC), a 600-bed publicly funded referral hospital in Georgetown, Guyana. OBJECTIVE: To assess spirometry quality and diagnostic outcomes 2 years after the introduction of spirometry into routine clinical practice at GPHC. DESIGN: We performed a retrospective review of 476 consecutive spirometry assessments performed from November 2013 to November 2015. We assessed the proportion and trend of spirometry tests meeting acceptability criteria, along with diagnostic interpretations and spirometry laboratory referral patterns. RESULTS: Overall, 80.4% of the 454 initial spirometry measurements on unique patients met the acceptability criteria, with no significant change in the proportion of acceptable spirometry over the study period (P = 0.450). Of the 369 (81.3%) first tests considered interpretable, 139 (30.6%) were normal, 151 (33.3%) were obstructive, 54 (11.9%) were suggestive of a restrictive pattern, 25 (5.5%) were suggestive of a mixed disorder and 119 (26.2%) tests met the definition of reversibility. CONCLUSION: Over a 2-year period, high-quality spirometry was performed in GPHC, a publicly funded hospital in a middle-income country with no pre-existing specialised respiratory service.

Interpretation of transbronchial lung biopsies from lung transplant recipients: inter- and intraobserver agreement.

BACKGROUND: Transbronchial lung biopsy results are crucial for the management of lung transplant recipients. Little information is available regarding the reliability and reproducibility of the interpretation of transbronchial lung biopsies. OBJECTIVE: To examine the inter-reader variability between two lung pathologists with expertise in lung transplantation. METHODS: Fifty-nine transbronchial lung biopsy specimens were randomly selected. Active infection had been excluded in all cases. The original interpretations (as per the Lung Rejection Study Group) for acute rejection grade included 19 biopsies scored as A0 (none), 14 scored as A1 (minimal), 12 as A2 (mild), 11 as A3 (moderate) and three as A4 (severe). The pathologists worked independently without clinical information or knowledge of the original interpretation. The specimens were graded using the Lung Rejection Study Group criteria for acute rejection (grades A0 to A4), airway inflammation (grades B0 to B4) and bronchiolitis obliterans (C0 absent and C1 present). Between-reader agreement for each category was analyzed using a Kappa statistic. RESULTS: Because many transplant specialists initiate augmented immunosuppression with biopsy grades of A2 or higher, results for each reader were dichotomized as A0/A1 versus A2/A3/A4. Using this dichotomy, there was only moderate agreement (kappa 0.470, P < 0.001) between readers. For categories B and C, the results were dichotomized for the absence or presence of airway inflammation and bronchiolitis obliterans, respectively. The level of agreement between readers was fair for category B (kappa 0.333, P = 0.014) and poor for category C (kappa 0.166, P = 0.108). The intrareader agreement for acute rejection was substantial (kappa 0.795, P = 0.0001; kappa 0.676, P = 0.0001). CONCLUSIONS: Because the agreement between expert pathologists is only modest, optimum clinical decision-making requires that transbronchial lung biopsy results be used in an integrated clinical context.

Impaired exercise performance after successful liver transplantation.

BACKGROUND: Recipients of heart, lung, and kidney transplants have impaired peak exercise performance (peak Vo2 40% to 60% predicted, reduced anaerobic threshold [AT]) without evidence of ventilatory or cardiac limitations. The aim of this study was to determine whether similar exercise impairment occurs in liver transplant recipients. METHODS: We studied eight healthy liver transplant recipients (age 42+/-9 [SD] years, 6 male, 31+/-13 months posttransplant). Immunosuppression included FK506 or cyclosporine, azathioprine or mycophenolate mofetil, and prednisone. Subjects underwent lung function testing and cardiopulmonary exercise testing on a cycle ergometer. RESULTS: Peak exercise oxygen consumption (Vo2) was 22+/-8 ml/min/kg (66+/-20% predicted maximum). No subject demonstrated exercise desaturation or ventilatory limitation (peak minute ventilation 55+/-8% predicted maximum voluntary ventilation). Peak heart rate was 87+/-8% of predicted maximum. Early AT was evident (1.2+/-0.34 L/min, 48+/-11% predicted Vo2max). CONCLUSIONS: Liver transplant recipients exhibit impaired peak exercise performance similar to that observed after other solid organ transplants, possibly as a result of chronic deconditioning or myopathy related to immunosuppressive medications.

Regional pulmonary perfusion following human heart-lung transplantation.

Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

Choice of therapy in chronic ischemic heart disease.

The choice of therapy in chronic ischemic heart disease depends on identifying the underlying mechanism. Ambulatory monitoring provides a means of identifying those patients in whom increased myocardial oxygen demand is the most important mechanism and who will respond to a beta blocker. In contrast, those patients with coronary spasm are best treated with a calcium antagonist. The history of angina pectoris and the time of onset may, in itself, be misleading. Detailed ambulatory monitoring studies show that nocturnal angina is frequently due to increased myocardial oxygen demand and in such circumstances should be treated by careful control of the heart rate using a beta blocker without intrinsic sympathomimetic activity. Other factors that will influence the choice of medical therapy must be considered. Smoking is particularly important because it not only acts detrimentally in terms of increased myocardial oxygen demand, but may also interfere with the metabolism of those antianginal agents that are metabolized in the liver. The importance of silent myocardial ischemia has been emphasized recently, and studies using ambulatory pulmonary artery monitoring have shown that silent ischemic episodes have the same significance in terms of hemodynamic effects as painful ischemic episodes. The therapeutic and prognostic implications of these findings need to be explored.

Should we treat silent ischaemic?

24-hour ambulatory monitoring of the ST segment in patients with angina has shown that ST segment depression may be accompanied by angina pectoris, but it occurs equally often without any symptoms. Approximately half of all episodes of ST segment depression are accompanied by chest pain. Doubt has been expressed as to the significance of ST segment changes that occur in the absence of chest pain, but haemodynamic studies and nuclear imaging have shown that such changes are accompanied by alterations in left ventricular filling pressure. Ambulatory pulmonary artery monitoring has also shown that silent ST segment depression is accompanied by a significant increase in pulmonary artery diastolic pressure, and this does not differ from painful episodes of ST segment depression. Studies using ambulatory monitoring have shown that antianginal drugs are capable of reducing the frequency of ST segment depression accompanied by pain. We have recently performed studies investigating the use of antianginal medications; i.e. beta-blocking drugs with and without sympathomimetic activity, alpha-beta-blocking drugs, calcium antagonists and nitrates in the treatment of both painful and painless ST segment depression. These studies have shown that the effect of these drugs on painless episodes is similar to their effect on painful episodes of myocardial ischaemia. Although the prognostic implications of silent ischaemia and the importance of these therapeutic findings are unknown, it is well known that approximately one-quarter of all myocardial infarctions occur without chest pain. Moreover, recent investigations in unstable angina show that silent myocardial ischaemia is an important predictor of future coronary events.

Quality adjusted life years added by treatment of obstructive sleep apnea.

We assessed the impact of treatment with nasal continuous positive airway pressure (nCPAP) on the quality of life of 19 patients with obstructive sleep apnea (OSA). We measured the utility for the patients' health states before and with treatment using the standard gamble approach. The study group had an average age of 57 years and had been on treatment for a mean of 9.5 months. For all the patients, the polysomnographic indicators of OSA disease severity improved markedly with treatment. For nine of the 12 symptoms most commonly associated with OSA, the patients reported improvement during treatment. The mean utility and the standard deviation obtained with the standard gamble method were 0.87 +/- 0.17 on treatment and 0.63 +/- 0.29 pretreatment. The difference in utility between treatment and pretreatment health states was combined with the life expectancy of each patient to generate the number of quality adjusted life years (QALYs) considered equivalent to the impact of treatment. This resulted in an average gain of 5.4 QALYs. When we related this impact to the cost of treatment, we obtained a cost-utility ratio between Can $3,397 and Can $9,792 per QALY added. These costs are relatively small when compared to the cost per QALY for many other clinical interventions. Hence, nCPAP clearly offers the prospect for a well-tolerated therapy with a very favorable cost-utility ratio.

The effects of changes in ventilation and cardiac output on expired nitric oxide.

The measurement of nitric oxide (NO) in expired gas is being increasingly reported in disease states such as sepsis, heart failure, and asthma. However, the effects of changes in ventilatory and cardiac parameters on expired NO are not known. Therefore, we assessed the effects of changes in minute ventilation (VE), ventilatory pattern, and cardiac output on expired gas NO levels in five anesthetized, intubated pigs. The animals were mechanically ventilated at three settings for each of respiratory rate (12 to 14, 16 to 18, and 22 to 24/min) and tidal volume (10, 15, and 20 mL/kg) applied in random sequence, yielding nine ventilatory patterns and a range of VE (3.7+/-0.1 to 13.2+/-0.8 L/min). When VE was increased, expired NO concentration declined slightly (r=-0.40, p<0.01), but the rate of excretion of NO in expired gas increased significantly (r=0.60, p<0.01). In contrast, when cardiac output was increased progressively from 3.6+/-0.1 to 4.7+/-0.3 and 5.8+/-0.4 L/min (p<0.01) by volume loading during constant eucapneic ventilation, there was no change in expired NO. Changes in VE over a physiologic range significantly affect the measurement of NO in expired gas, whereas short-term changes in cardiac output do not. To facilitate comparison between studies, we suggest that the measurement of expired NO should be reported in conjunction with data on VE.

The hypotensive effect of L-arginine is associated with increased expired nitric oxide in humans.

Endothelial metabolism of L-arginine to L-citrulline and the potent vasodilator, nitric oxide (NO), is important in the regulation of vascular tone and resting BP. L-arginine improves abnormal endothelium-dependent vasodilation in the setting of hypercholesterolemia and has a vasodilatory effect in normal vessels, effects presumed to be mediated through increased endogenous NO production, although this has not been established by direct measurement of NO. In a randomized, placebo-controlled, crossover trial, 10 healthy male subjects received a 30-min infusion of 0.5 g/kg L-arginine hydrochloride. Subjects underwent continuous monitoring of BP and heart rate (HR) as well as intermittent determination of mixed expired NO concentration and plasma L-arginine and L-citrulline levels. Infusion of L-arginine produced a significant fall in mean BP with a peak effect of -9.3 +/- 0.9% (p<0.005). The hemodynamic effects of L-arginine were associated with an increase in mixed expired NO concentration (FeNO) of 55 +/- 15% (p<0.005) from 15 +/- 2 to 21 +/- 3 parts per billion (ppb) and an increase in the rate of pulmonary NO excretion of 118 +/- 45% (p<0.005), as well as a rise in plasma L-citrulline from 25 +/- 4 to 46 +/- 5 micromol/l (p<0.005). There was a significant correlation between the hypotensive response to L-arginine and the increase in expired NO (r=-0.68, p<0.05). The hypotensive effect of L-arginine in humans appears to be mediated, at least in part, by NO synthase metabolism of L-arginine and increased endogenous NO production as indicated both by increased plasma L-citrulline and by increased expired NO.

Ventilatory muscle support in respiratory failure with nasal positive pressure ventilation.

Long-term intermittent mechanical ventilation results in improvements in ventilatory performance and clinical status between ventilation sessions in patients with chronic respiratory failure. The application of intermittent positive pressure ventilation through a nasal mask (NPPV) is a simple, noninvasive method for the provision of chronic intermittent ventilatory support. We investigated the effects of NPPV on inspiratory muscle activity in three normal subjects and nine patients with acute or chronic ventilatory failure due to restrictive (four subjects) or obstructive (five subjects) respiratory disorders. NPPV resulted in reductions of phasic diaphragm electromyogram amplitude to 6.7 +/- 0.7 percent (mean +/- SEM) of values obtained during spontaneous breathing in the normal subjects, 6.4 +/- 3.2 percent in the restrictive group, and 8.3 +/- 5.1 percent in the obstructive group. Simultaneous decreases in activity of accessory respiratory muscles were observed. The reductions in inspiratory muscle activity were confirmed by the finding of positive intrathoracic pressure swings on inspiration in all subjects. With NPPV, oxygen saturation and PCO2 remained stable or improved as compared with values obtained during spontaneous breathing. These results indicate that NPPV can noninvasively provide ventilatory support while reducing inspiratory muscle energy expenditure in acute and chronic respiratory failure of diverse etiology. Long-term assisted ventilation with NPPV may be useful in improving ventilatory performance by resting the inspiratory muscles.

Prolonged survival after heart-lung transplantation in systemic lupus erythematosus.

Patients with multisystem involvement of connective tissue disorders are generally excluded from consideration for heart-lung and lung transplantation because of profound donor organ shortages. A 23-year-old woman with systemic lupus erythematosus (SLE) was referred for evaluation of severe, progressive pulmonary hypertension. She underwent an uneventful heart-lung transplant and received cyclosporine A, azathioprine, and prednisone on a long-term basis. Bronchiolitis obliterans resulted in the development of moderate airflow obstruction 18 months after transplantation, but the process was stabilized with augmented immunosuppression consisting of high-dose parenterally administered corticosteroids, and subsequently a course of antithymocyte globulin. Four years after transplant, despite the persistence of reduced complement levels, the patient remains functionally well without clinical manifestations of SLE. This patient's long-term successful outcome indicates that connective tissue disorders such as SLE do not necessarily represent absolute contraindications to heart-lung and lung transplantation.

Local determinants of response to endobronchial high-dose rate brachytherapy in bronchogenic carcinoma.

STUDY OBJECTIVE: We evaluated bronchoscopic tumor appearance and tumor location as determinants of response to high-dose rate brachytherapy (HDR-BT) in patients with symptomatic unresectable bronchogenic carcinoma previously treated with external-beam irradiation. PATIENTS AND METHODS: Thirty patients with symptomatic endobronchial bronchogenic carcinoma who had previously completed external irradiation were divided into two groups based on whether the initial bronchoscopic appearance showed an endoluminal mass or submucosal infiltration/extrinsic compression. Furthermore, patients were also classified based on tumor location: central (trachea or mainstem bronchi) and peripheral (lobar or segmental bronchi). Patients underwent three treatments of 800 cGy intraluminal irradiation at 2-week intervals, with follow-up evaluation 4 weeks later. We evaluated response in tumor extent based on bronchoscopic and chest radiograph appearance, as well as symptoms with standardized scales. RESULTS: Fifteen of 24 patients who underwent follow-up bronchoscopy had reductions in the degree of endobronchial obstruction. Seven of 24 patients had radiographic improvement in the extent of atelectasis. Patients with both tumor appearances (endoluminal and submucosal/extrinsic compression) had significant improvements following HDR-BT with regard to hemoptysis. Patients with submucosal disease also had improvement in cough. Patients with peripheral tumors had better rates of response for hemoptysis and cough than did those with central tumors. CONCLUSION: HDR-BT may result in symptomatic improvement in patients with bronchogenic carcinoma, whether characterized endoscopically as endoluminal projection or submucosal infiltration/extrinsic compression. Peripheral tumors have better rates of response than central tumors, possibly on the basis of less extensive disease.

Changes in obstructive sleep apnea characteristics through the night.

It was our impression that the respiratory parameters in obstructive sleep apnea (OSA) worsened as the night progressed. To confirm this, we review polysomnographic studies from 66 patients with apnea-hypopnea indices (AHI) of 40 to 125 events per hour, dividing bed time into equal quartiles. As the night progressed, the mean apnea duration (MAD) increased from 27.2 s to 34.6 s (p < 0.0001), mainly from increases during NREM sleep. The proportion of time spent in apnea increased from 54 to 71% (p < 0.0001) due to increases in both MAD and the proportion of REM sleep (from 2.8 to 14.7% of the total sleep time). The AHI did not change significantly between quartiles. Even though preapneic oxygen saturation did not change and apnea duration increased as the night progressed, the end-apneic saturation did not decrease, hence the rate of oxygen desaturation decreased. Also, it was found that patients with an AHI greater than 65 events per hour increased their proportion of time spent in apnea significantly more than those with an AHI smaller than 65, as the night progressed. In the patients with an AHI greater than 85, this was due to both an increase in MAD and AHI. In conclusion, in patients with an AHI greater than 40 events per hour, the severity of apnea increased as the night progressed due to lengthening of MAD, increased proportion of REM sleep, and in the most severe patients, also an increase in AHI. Even though the exact pathophysiologic mechanisms for the observed changes are unknown, a decrease in respiratory muscle effort with consequent decrease in oxygen consumption may explain both the lengthening of the apneas and the decrease in the rate of oxygen desaturation.

Exertional dyspnea and ventilation in hyperthyroidism.

Dyspnea is recognized to be an important feature in patients with hyperthyroidism at rest and during exercise. However, its etiology is not well-understood. Since dyspnea is thought to be related to the perception of excessive ventilatory effort, we explored the possibility that dyspnea in these patients might be related to an inappropriate ventilatory response to the increased metabolic rate. We studied 11 hyperthyroid patients and 11 age- and sex-matched controls, performing spirometry, lung volumes, mouth pressure measurements, and incremental exercise test. Central drive was estimated by measuring P0.1 and sensation of dyspnea by the Borg scale. We found that hyperthyroid patients (1) have higher ventilation than normal subjects during exercise even when corrected for VCO2 levels; (2) this increased ventilation is secondary to increased central drive which is correlated to the T3ria level (r = 0.85, p less than 0.01); (3) hyperthyroid patients are more dyspneic than controls; and (4) the increased drive can be normalized by beta-blockade. We conclude that the main ventilatory abnormality in hyperthyroid patients is an inappropriate increase in respiratory drive, possibly secondary to increased adrenergic stimulation.

Disseminated infection after intravesical BCG immunotherapy. Detection of organisms in pulmonary tissue.

A 57-year-old man undergoing intravesical immunotherapy with BCG for transitional cell bladder carcinoma presented with dyspnea, fever, hypoxemia, and a diffuse micronodular pattern on chest radiograph. Transbronchial biopsy specimen revealed widespread noncaseating granulomas, and acid-fast bacilli were identified in sputum as well as in the biopsy tissue. The patient's condition responded promptly to antituberculous antibiotics given in conjunction with corticosteroids. Although no growth was evident on TB culture of the specimens, the presence of organisms indicates a probable infectious cause of the pulmonary disease process.

Maximal exercise testing for the selection of heart transplantation candidates: limitation of peak oxygen consumption.

BACKGROUND: Peak exercise oxygen consumption (peak VO2), which is considered an indicator of prognosis in advanced heart failure, is currently being used as a major criterion in many centers for the selection of candidates for heart transplantation. Available studies suggest that patients with peak VO2 < 14 mL/min/kg have improved survival and significant functional benefit with transplantation. Since patients may terminate symptom-limited exercise tests for a variety of reasons, peak VO2 does not necessarily reflect maximal VO2, leading to the possibility of inappropriate selection for transplantation. Therefore, we investigated the proportion of transplant candidates referred for exercise testing considered to have achieved maximal results from studies. METHODS: Fifty-five patients with heart failure, aged 51+/-9 years, (mean +/- SD) underwent maximum symptom-limited exercise tests on a cycle ergometer utilizing a Jones stage 1 incremental protocol. Tests were considered maximal if subjects achieved peak heart rate (HR) > 85% predicted ("cardiocirculatory limitation") or peak minute ventilation (VE) > 85% predicted ("ventilatory limitation"), and achieved an anaerobic threshold (AT) by noninvasive measures. RESULTS: Seven tests were terminated because of chest pain, ST-segment abnormalities, or ventricular arrhythmias. Of the remaining 48 studies, the reasons for stopping exercise were leg fatigue in 52%, dyspnea in 16%, and both symptoms in 23%. Sixteen of the 48 patients (33%) had peak VO2 < 14 mL/min/kg. In 8 of these 16 patients, both peak HR and VE were < 85% predicted. Of these eight without apparent HR or ventilatory limitation, none had oxygen desaturation below 90% or fall in BP, two were in atrial fibrillation, and only three had evidence that an AT was achieved. CONCLUSIONS: Among the patients with peak VO2 < 14 mL/min/kg, there were no objective signs of a cardiocirculatory or a respiratory limitation to exercise in half of them, and 31% did not achieve an AT either, thus not meeting any criteria to support evidence of maximal exercise. Exercise tests without objective evidence of cardiocirculatory or ventilatory limitation may not represent maximal performance. Consequently, peak VO2 may misclassify an appreciable proportion of candidates if the test results are submaximal. CLINICAL IMPLICATIONS: Clinical exercise studies indicating low peak VO2 must be interpreted in the context of whether a defined objective exercise limitation is evident to avoid biasing the selection of heart transplant candidates.

Cardiac arrhythmias during exercise in severe chronic obstructive pulmonary disease.

We studied the effect of maximal exercise on the prevalence of arrhythmias in 122 subjects with severe COPD. At rest, ten subjects had supraventricular arrhythmias while 13 had unifocal VPB greater than or equal to 6/min or ventricular bigeminy. At peak exercise, six subjects had supraventricular arrhythmias while 24 had VAs. Univariate and multivariate analysis with logistic regression did not show relationships between exercise-related cardiac arrhythmias and the severity of pulmonary disease, oxyhemoglobin desaturation or ECG evidence of chronic lung disease. Exercise-related arrhythmias were significantly associated with the presence of arrhythmias at rest and 87 percent of subjects who had no arrhythmias at rest did not have any during exercise. In patients with COPD, the development of potentially serious arrhythmias during exercise is uncommon without clinically apparent CAD or arrhythmias at rest. However, routine cardiac monitoring during exercise testing should not be abandoned in this population since VAs can occur despite their absence at rest.