Prognostic value of exercise longitudinal right ventricular free wall strain in patients with sickle cell disease.

Longitudinal right ventricular free wall strain (RVFWS) has been identified as an independent prognostic marker in patients with pulmonary hypertension. Little is known however about the prognostic value of RVFWS in patients with sickle cell (SC) disease, particularly during exercise. We therefore examined the prognostic significance of RVFWS both at rest and with exercise in patients with SC disease and normal resting systolic pulmonary artery pressure (SPAP). Consecutive patients with SC disease referred for bicycle ergometer stress echocardiography (SE) were enrolled ftom July 2019 to January 2021. All patients had measurable tricuspid regurgitation velocity (TRV). Conventional echocardiography parameters, left ventricular global longitudinal strain (LVGLS), RVFWS, and ventriculoarterial coupling indices (TAPSE/SPAP and RVFWS/SPAP) were assessed at rest and peak exercise. Repeat SE was performed at a median follow-up of 2 years. The cohort consisted of 87 patients (mean age was 31 ± 11 years, 66% females). All patients had normal resting TRV < 2.8 m/s, RVFWS and LVGLS at baseline. There were 23 (26%) patients who had peak stress RVFWS < 20%. They had higher resting and peak stress TRV and SPAP, but lower resting and peak stress TAPSE/SPAP, RVFWS/SPAP, and LVGLS as well as lower peak stress cardiac output when compared to patients with peak stress RVFWS ≥ 20% (p < 0.05). Patients with baseline peak stress RVFWS < 20% had a significant decrease in exercise performance at follow-up (7.5 ± 2.7 min at baseline vs. 5.5 ± 2.8 min at follow-up, p < 0.001). In the multivariate analysis, baseline peak stress RVFWS was the only independent predictor of poorer exercise performance at follow-up [odds ratio 8.2 (1.2, 56.0), p = 0.033]. Among patients with SC disease who underwent bicycle ergometer SE, a decreased baseline value of RVFWS at peak stress predicted poorer exercise time at follow-up.

Clinical Implementation of Different Strategies for Exercise-Based Rehabilitation in Kidney and Liver Transplant Recipients: A Pilot Study. / Implementação Clínica de Diferentes Estratégias para Reabilitação Baseada em Exercícios em Receptores de Transplante de Rim e Fígado: Um Estudo Piloto.

BACKGROUND: Cardiovascular disease is among the leading causes of death in solid organ transplant recipients with a functional graft. Although these patients could theoretically benefit from exercise-based rehabilitation (EBR) programs, their implementation is a challenge. OBJECTIVE: We present our initial experience on different delivery modes of a pilot EBR program in kidney and liver transplant recipients. METHODS: Thirty-two kidney or liver transplant recipients were invited for a 6-month EBR program delivered at the hospital gym, community gym or at home, according to the patient's preference. The significance level adopted was 5%. RESULTS: Ten patients (31%) did not complete their program. Among the 22 who did, 7 trained at the hospital gym, 7 at the community gym, and 8 at home. The overall effect was an 11.4% increase in maximum METs (Hedges' effect size g = 0.39). The hospital gym group had an increase in METs of 25.5% (g= 0.58, medium effect size) versus 10% (g= 0.25), and 6.5% (g= 0.20) for the community gym and home groups, respectively. There was a beneficial effect on systolic and diastolic blood pressures, greater for the hospital gym (g= 0.51 and 0.40) and community gym (g= 0.60 and 1.15) groups than for the patients training at home (g= 0.07 and 0.10). No significant adverse event was reported during the follow-up. CONCLUSION: EBR programs in kidney and liver transplant recipients should be encouraged, even if they are delivered outside a hospital gym, since they are safe with positive effects on exercise capacity and cardiovascular risk factors.

FUNDAMENTO: A doença cardiovascular está entre as principais causas de morte entre pacientes transplantados. Embora esses pacientes possam teoricamente se beneficiar de programas de reabilitação baseada em exercícios (RBE), sua implementação ainda é um desafio. OBJETIVO: Apresentamos nossa experiência inicial em diferentes modos de realização de um programa piloto de RBE em receptores de transplante de rim e fígado. MÉTODOS: Trinta e dois pacientes transplantados renais ou hepáticos foram convidados para um programa de RBE de 6 meses realizado na academia do hospital, na academia comunitária ou em casa, de acordo com a preferência do paciente. O nível de significância adotado foi de 5%. RESULTADOS: Dez pacientes (31%) não completaram o programa. Entre os 22 que completaram, 7 treinaram na academia do hospital, 7 na academia comunitária e 8 em casa. O efeito geral foi um aumento de 11,4% nos METs máximos (tamanho do efeito de Hedges g = 0,39). O grupo de academia hospitalar teve um aumento nos METs de 25,5% (g = 0,58, tamanho de efeito médio) versus 10% (g = 0,25) e 6,5% (g = 0,20) para os grupos de academia comunitária e em casa, respectivamente. Houve efeito benéfico nas pressões arteriais sistólica e diastólica, maior para os grupos academia hospitalar (g= 0,51 e 0,40) e academia comunitária (g= 0,60 e 1,15) do que para os pacientes treinando em casa (g= 0,07 e 0,10). Nenhum evento adverso significativo foi relatado durante o seguimento. CONCLUSÃO: Programas de RBE em receptores de transplante de rim e fígado devem ser incentivados, mesmo que sejam realizados fora da academia do hospital, pois são seguros com efeitos positivos na capacidade de exercício e nos fatores de risco cardiovascular.

Implementação Clínica de Diferentes Estratégias para Reabilitação Baseada em Exercícios em Receptores de Transplante de Rim e Fígado: Um Estudo Piloto / Clinical Implementation of Different Strategies for Exercise-Based Rehabilitation in Kidney and Liver Transplant Recipients: A Pilot Study

Resumo Fundamento: A doença cardiovascular está entre as principais causas de morte entre pacientes transplantados. Embora esses pacientes possam teoricamente se beneficiar de programas de reabilitação baseada em exercícios (RBE), sua implementação ainda é um desafio. Objetivo: Apresentamos nossa experiência inicial em diferentes modos de realização de um programa piloto de RBE em receptores de transplante de rim e fígado. Métodos: Trinta e dois pacientes transplantados renais ou hepáticos foram convidados para um programa de RBE de 6 meses realizado na academia do hospital, na academia comunitária ou em casa, de acordo com a preferência do paciente. O nível de significância adotado foi de 5%. Resultados: Dez pacientes (31%) não completaram o programa. Entre os 22 que completaram, 7 treinaram na academia do hospital, 7 na academia comunitária e 8 em casa. O efeito geral foi um aumento de 11,4% nos METs máximos (tamanho do efeito de Hedges g = 0,39). O grupo de academia hospitalar teve um aumento nos METs de 25,5% (g = 0,58, tamanho de efeito médio) versus 10% (g = 0,25) e 6,5% (g = 0,20) para os grupos de academia comunitária e em casa, respectivamente. Houve efeito benéfico nas pressões arteriais sistólica e diastólica, maior para os grupos academia hospitalar (g= 0,51 e 0,40) e academia comunitária (g= 0,60 e 1,15) do que para os pacientes treinando em casa (g= 0,07 e 0,10). Nenhum evento adverso significativo foi relatado durante o seguimento. Conclusão: Programas de RBE em receptores de transplante de rim e fígado devem ser incentivados, mesmo que sejam realizados fora da academia do hospital, pois são seguros com efeitos positivos na capacidade de exercício e nos fatores de risco cardiovascular.

Abstract Background: Cardiovascular disease is among the leading causes of death in solid organ transplant recipients with a functional graft. Although these patients could theoretically benefit from exercise-based rehabilitation (EBR) programs, their implementation is a challenge. Objective: We present our initial experience on different delivery modes of a pilot EBR program in kidney and liver transplant recipients. Methods: Thirty-two kidney or liver transplant recipients were invited for a 6-month EBR program delivered at the hospital gym, community gym or at home, according to the patient's preference. The significance level adopted was 5%. Results: Ten patients (31%) did not complete their program. Among the 22 who did, 7 trained at the hospital gym, 7 at the community gym, and 8 at home. The overall effect was an 11.4% increase in maximum METs (Hedges' effect size g = 0.39). The hospital gym group had an increase in METs of 25.5% (g= 0.58, medium effect size) versus 10% (g= 0.25), and 6.5% (g= 0.20) for the community gym and home groups, respectively. There was a beneficial effect on systolic and diastolic blood pressures, greater for the hospital gym (g= 0.51 and 0.40) and community gym (g= 0.60 and 1.15) groups than for the patients training at home (g= 0.07 and 0.10). No significant adverse event was reported during the follow-up. Conclusion: EBR programs in kidney and liver transplant recipients should be encouraged, even if they are delivered outside a hospital gym, since they are safe with positive effects on exercise capacity and cardiovascular risk factors.

Exercise capacity and paroxysmal atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia among patients with hypertrophic cardiomyopathy (HCM). The relationship between paroxysmal AF and exercise capacity in this population is incompletely understood. METHODS: Patients with HCM underwent symptom-limited cardiopulmonary testing with expired gas analysis at Stanford Hospital between October 2006 and October 2012. Baseline demographics, medical histories and resting echocardiograms were obtained for all subjects. Diagnosis of AF was established by review of medical records and baseline ECG. Those with paroxysmal AF were in sinus rhythm at the time of cardiopulmonary testing with expired gas analysis. Exercise intolerance was defined as peak VO2<20 mL/kg/min. We used multivariate logistic regression to evaluate the association between exercise intolerance and paroxysmal AF. RESULTS: Among the 265 patients recruited, 55 had AF (28 paroxysmal and 27 permanent). Compared with those without AF, subjects with paroxysmal AF were older, more likely to use antiarrhythmic and anticoagulant medications, and had larger left atria. Patients with paroxysmal AF achieved lower peak VO2 (21.9±9.2 mL/kg/min vs 26.9±10.8 mL/kg/min, p=0.02) and were more likely to have exercise intolerance (61% vs 28%, p<0.001) compared with those without AF. After adjustment for age, sex and body mass index (BMI) exercise intolerance remained significantly associated with paroxysmal AF (OR 4.65, 95% CI 1.83 to 11.83, p=0.001). CONCLUSIONS: Patients with HCM and paroxysmal AF demonstrate exercise intolerance despite being in sinus rhythm at the time of exercise testing.

The effect of sport on computerized electrocardiogram measurements in college athletes.

BACKGROUND: Broad criteria for abnormal electrocardiogram (ECG) findings, requiring additional testing, have been recommended for preparticipation exams (PPE) of athletes. As these criteria have not considered the sport in which athletes participate, we examined the effect of sports on the computerized ECG measurements obtained in college athletes. METHODS: During the Stanford 2007 PPE, computerized 12-lead ECGs (Schiller AG) were obtained in 641 athletes (350 male/291 female, age 19.5 ± 2 years). Athletes were engaged in 22 different sports and were grouped into 16 categories: baseball/softball, basketball, crew, crosscountry, fencing, field events, football linemen, football other positions, golf, gymnastics, racquet sports, sailing, track/field, volleyball, water sports, and wrestling. The analysis focused on ECG leads V2, aVF and V5 which provide a three-dimensional representation of the heart's electrical activity. As marked ECG differences exist between males and females, the data are presented by gender. RESULTS: In males, ANOVA analysis yielded significant ECG differences between sports for heart rate, QRS duration, QTc, J-amplitude in V2 and V5, spatial vector length (SVL) of the P wave, SVL R wave, and SVL T wave, and RS(sum) (p < 0.05). In females ECG differences between sports were found for heart rate, QRS duration, QRS axis and SVL T wave (p < 0.05). Poor correlations were found between body dimensions and ECG measurements (r < 0.50). CONCLUSIONS: Significant ECG changes exist between college athletes participating in different sports, and these differences were more apparent in males than females. Therefore, sport-specific ECG criteria for abnormal ECG findings should be developed to obtain a more useful approach to ECG screening in athletes.

Effect of gender on computerized electrocardiogram measurements in college athletes.

BACKGROUND: Broad criteria for classifying an electrocardiogram (ECG) as abnormal and requiring additional testing prior to participating in competitive athletics have been recommended for the preparticipation examination (PPE) of athletes. Because these criteria have not considered gender differences, we examined the effect of gender on the computerized ECG measurements obtained on Stanford student athletes. Currently available computer programs require a basis for "normal" in athletes of both genders to provide reliable interpretation. METHODS: During the 2007 PPE, computerized ECGs were recorded and analyzed on 658 athletes (54% male; mean age, 19 +/- 1 years) representing 22 sports. Electrocardiogram measurements included intervals and durations in all 12 leads to calculate 12-lead voltage sums, QRS amplitude and QRS area, spatial vector length (SVL), and the sum of the R wave in V5 and S wave in V2 (RSsum). RESULTS: By computer analysis, male athletes had significantly greater QRS duration, PR interval, Q-wave duration, J-point amplitude, and T-wave amplitude, and shorter QTc interval compared with female athletes (all P < 0.05). All ECG indicators of left ventricular electrical activity were significantly greater in males. Although gender was consistently associated with indices of atrial and ventricular electrical activity in multivariable analysis, ECG measurements correlated poorly with body dimensions. CONCLUSION: Significant gender differences exist in ECG measurements of college athletes that are not explained by differences in body size. Our tables of "normal" computerized gender-specific measurements can facilitate the development of automated ECG interpretation for screening young athletes.

Addition of the electrocardiogram to the preparticipation examination of college athletes.

OBJECTIVE: Although the use of standardized cardiovascular (CV) system-focused history and physical examination is recommended for the preparticipation examination (PPE) of athletes, the addition of the electrocardiogram (ECG) has been controversial. Because the impact of ECG screening on college athletes has rarely been reported, we analyzed the findings of adding the ECG to the PPE of Stanford athletes. DESIGN: For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database. SETTING: Although the use of standardized CV-focused history and physical examination are recommended for the PPE of athletes, the addition of the ECG has been controversial. Because the feasibility and outcomes of ECG screening on college athletes have rarely been reported, we present findings derived from the addition of the ECG to the PPE of Stanford athletes. For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database. MAIN OUTCOME MEASURES: Six hundred fifty-eight recordings were obtained (54% men, 10% African-American, mean age 20 years) representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete right bundle branch block (RBBB) (13%), right axis deviation (RAD) (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for left ventricular hypertrophy (LVH) were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7%, and only 5 men had abnormal Q-waves. Sixty-three athletes (10%) were judged to have distinctly abnormal ECG findings possibly associated with conditions including hypertrophic cardiomyopathy or arrhythmogenic right ventricular dysplasia/cardiomyopathy. These athletes were offered further testing but this was not mandated according to the research protocol. RESULTS: Six hundred fifty-three recordings were obtained (54% men, 7% African American, mean age 20 years), representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete RBBB (13%), RAD (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for LVH were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7% and only 5 men had abnormal Q-waves. Sixty-five athletes (10%) were judged to have distinctly abnormal ECG findings suggestive of arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy, and/or biventricular hypertrophy. These athletes will be submitted to further testing. CONCLUSIONS: Mass ECG screening is achievable within the collegiate setting by using volunteers when the appropriate equipment is available. However, the rate of secondary testing suggests the need for an evaluation of cost-effectiveness for mass screening and the development of new athlete-specific ECG interpretation algorithms.

Rest premature ventricular contractions on routine ECG and prognosis in heart failure patients.

BACKGROUND: Premature ventricular contractions (PVC) at rest are frequently seen in heart failure (HF) patients but conflicting data exist regarding their importance for cardiovascular (CV) mortality. This study aims to evaluate the prognostic value of rest PVCs on an electrocardiogram (ECG) in patients with a history of clinical HF. METHODS AND RESULTS: We considered 352 patients (64 + or - 11 years; 7 females) with a history of clinical HF undergoing treadmill testing for clinical reasons at the Veterans Affairs Palo Alto Health Care System (VAPAHCS) (1987-2007). Patients with rest PVCs were defined as having > or = 1 PVC on the ECG prior to testing (n = 29; 8%). During a median follow-up period of 6.2 years, there were 178 deaths of which 76 (42.6%) were due to CV causes. At baseline, compared to patients without rest PVCs, those with rest PVCs had a lower ejection fraction (EF) (30% vs 45%) and the prevalence of EF < or = 35% was higher (75% vs 41%). They were more likely to have smoked (76% vs 55%).The all-cause and CV mortality rates were significantly higher in the rest PVCs group (72% vs 49%, P = 0.01 and 45% vs 20%, P = 0.002; respectively). After adjusting for age, beta-blocker use, rest ECG findings, resting heart rate (HR), EF, maximal systolic blood pressure, peak HR, and exercise capacity, rest PVC was associated with a 5.5-fold increased risk of CV mortality (P = 0.004). Considering the presence of PVCs during exercise and/or recovery did not affect our results. CONCLUSION: The presence of PVC on an ECG is a powerful predictor of CV mortality even after adjusting for confounding factors.

Exercise capacity at submaximal heart rate and prognosis.

INTRODUCTION: Submaximal exercise testing can be useful for individuals with limitations to performing maximal exercise. Recent studies suggested that a low workload at a heart rate 100 beats/minute (HR(100)) was associated with a greater risk of cardiovascular (CV) mortality than maximal exercise capacity. This study evaluated the prognostic value of METs achieved at HR(100) (METs(100)) in patients referred for treadmill testing. METHOD: We studied 1446 patients (56+/-12 years; 76 females) without heart failure or beta-blockers treatment (1997-2004). RESULTS: During a period of 7.0+/-2.3 years, 35 (2.5%) patients died from CV causes. Compared to survivors, the non-survivors were older (69+/-9 vs. 56+/-12 years, p<0.001); had a higher prevalence of diabetes (27% vs. 14%, p=0.04), coronary artery disease (57% vs. 25%, p<0.05) and stroke (9% vs. 2%, p<0.001). Non-survivors had lower Duke Treadmill Scores (DTS) (2.8+/-6.8 vs. 9.7+/-5.5; p<0.001) and exercise capacity (7.5+/-3.3 vs.11.0+/-3.8 METs, p<0.001). At HR(100), METs (median (range): 3.8 (2.8-4.0) vs. 3.5 (3.3-3.5)) and %HR reserve achieved (45+/-13% vs. 34+/-17%; p<0.001) were higher in non-survivors. In Cox model, age-adjusted METs(100) was not a significant predictor of CV mortality. In contrast, each one MET increase in exercise capacity was associated with a 17% increase in survival (HR=0.83, 95% CI 0.73-0.93, p=0.002). DTS was also a significant predictor of CV mortality. CONCLUSION: In our population, METs at HR(100) was not a significant predictor of CV mortality.

Adding an electrocardiogram to the pre-participation examination in competitive athletes: a systematic review.

No matter how rare, the death of young athletes is a tragedy. Can it be prevented? The European experience suggests that adding the electrocardiogram (ECG) to the standard medical and family history and physical examination can decrease cardiac deaths by 90%. However, there has not been a randomized trial to demonstrate such a reduction. While there are obvious differences between the European and American experiences with athletes including very differing causes of athletic deaths, some would highlight the European emphasis on public welfare vs the protection of personal rights in the USA. Even the authors of this systematic review have differing interpretation of the data: some of us view screening as a hopeless battle against Bayes, while others feel that the ECG can save lives. What we all agree on is that the USA should implement the American Heart Association 12-point screening recommendations and that, before ECG screening is mandated, we need to gather more data and optimize ECG criteria for screening young athletes.

Mechanisms of exercise intolerance in patients with hypertrophic cardiomyopathy.

AIM: To determine the relation between echocardiogram findings and exercise capacity in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Sixty-three patients (48 +/- 15 years) were referred for cardiopulmonary testing and exercise echocardiography. They were classified by morphology: proximal (n = 11), reverse curvature (n = 32), apical (n = 7), and concentric HCM (n = 13). There were more women in proximal and reverse curvature groups. Proximal HCM patients were older. Maximal left ventricular thickness was highest in reverse curvature group. At peak exercise, concentric HCM achieved the lowest percent predicted maximal Vo2. Excluding apical group, no significant differences in gradient were noted between groups. Overall, no statistically significant correlation was found between peak Vo2, wall thickness, and gradient. Significant correlations were noted between peak Vo2 and indexed left atrial (LA) volume (r = -0.52), lateral E' (r = 0.50), and lateral E/E' ratio (r = -0.46). A multivariate model including age, lateral E', indexed LA volume, and mitral A wave explained 46% of the variance in peak Vo2 (P = .01). CONCLUSION: Lateral E' and indexed LA volume are negatively correlated with functional capacity. Although patients with concentric morphology achieved the lowest peak Vo2, wall thickness and gradient did not predict exercise capacity.

Impact of ezetimibe on cholesterol subfractions in dyslipidemic cardiac transplant recipients receiving statin therapy.

BACKGROUND: Ezetimibe decreases cholesterol in cardiac transplant recipients intolerant to statins therapy. The effects of ezetimibe in addition to statins therapy and its relationship with the magnitude of dyslipidemia and statins utilization have not been studied in cardiac transplant recipients. METHODS: The design of this investigation was a retrospective case control study. Twenty-two patients receiving the combination of therapy of statins plus ezetimibe were compared with 43 patients treated with statins only. The endpoints were assessed after three months of follow-up. RESULTS: The addition of ezetimibe decreased low density lipoprotein-cholesterol by 25% compared with a 4% increase in patients receiving statins only. The impact of ezetimibe was similar regardless of the magnitude of dyslipidemia or statins dosage. Ezetimibe increase high density lipoprotein (HDL)-cholesterol only in patients with baseline HDL-cholesterol above 1.3 mM/L (p < 0.05). There was an asymptomatic, but significant increase in creatinine kinase level [+31.4 +/- 8.1 (ezetimibe) vs. + 1.5 +/- 5.0 mM/L (placebo); p = 0.005]. CONCLUSION: Ezetimibe therapy provides a significant reduction in most cholesterol subfractions regardless of the magnitude of dyslipidemia and statins dosage.

The blood pressure response to dynamic exercise testing: a systematic review.

Although blood pressure (BP) is measured routinely during exercise testing, its clinical significance is not fully understood or appreciated. As the number of studies has increased, conflicting data have emerged, partly due to differences in methodologies, populations studied, testing procedures, and definitions used for an abnormal BP response. This article attempts to review the literature studying the physiology and pathophysiology of the BP response to exercise testing and summarize the evidence for its diagnostic and prognostic applications.