Exercise-induced Left Ventricular Dysfunction Research Articles

Leg raise can detect exercise-induced pulmonary arterial wedge pressure elevation

Abstract Background Exercise-induced elevation of pulmonary arterial wedge pressure (PAWP) may show preclinical or exercise-induced left ventricular diastolic dysfunction. Invasive hemodynamic assessment during provocative maneuvers, like exercise and volume challenge, in these patients allows greater sensitivity to diagnose or exclude HFpEF. The aim of this study was to examine how the leg raise, which is a simple way to increase preload, can detect exercise-induced PAWP elevation. Methods Four hundred seventy-nine patients (60±14y.o, mean pulmonary arterial pressure (PAP) 19mmHg, PAWP 8mmHg, CTEPH /IPAH/CTD-PH/SOB unknown reason: 357/56/38/28pts) with near-normal PAP and normal PAWP at rest underwent symptom-limited exercise test using supine cycle ergometer with right heart catheter. Exercise-induced elevation in PAWP of over 20mmHg was defined as exercise-induced elevation group. Results ΔPAWP (after leg raise - rest) in the exercise-induced elevation group was significantly higher (6.0±4.1 vs. 2.7±3.9mmHg, p<0.001, in the older (age≥60y.o) group (n=276); 3.4±3.5 vs. 1.9±3.4mmHg, p<0.001, in the younger (age<60y.o) group (n=203)) than that in the non-elevation group after legs raise for cycle ergometer exercise. The area under the ROC curve for ΔPAWP was 0.72 (95% CI: 0.65–0.78) in the older and 0.64 (95% CI: 0.53–0.75) in the younger. In the older, the cut-off value for detect exercise-induced PAWP elevation of ΔPAWP was 4mmHg, with 72% sensitivity and 58% specificity. On the other hand, in the younger, the cut-off value was 3mmHg, with 69% sensitivity and 59% specificity. Conclusion Leg raise can easily detect occult left ventricular diastolic dysfunction. Funding Acknowledgement Type of funding source: None

Reversible exercise-induced left ventricular dysfunction in symptomatic patients with previous Takotsubo syndrome: insights from stress echocardiography.

Takotsubo syndrome (TTS) is usually associated with rapid and spontaneous recovery of left ventricular (LV) function. However, a proportion of patients may have persistent symptoms. This study aimed to determine the haemodynamic and LV contractile responses to exercise in these patients. Thirty symptomatic TTS patients referred for exercise echocardiography, a median of 15 months following the index TTS episode, were matched with 30 controls with normal exercise echocardiography. Beta-blockers were withheld prior to the test. LV volumes, ejection fraction (EF) and wall motion score index (WMSI), were measured at rest and stress. The TTS cohort were Caucasian women with mean age of 64.6 ± 7.4 years and similar coronary risk factor profile and EF to controls. Resting systolic blood pressure (SBP), LV end-diastolic volume, wall stress, and right ventricular fractional area change were higher in TTS patients compared with controls. Stress echo data showed similar exercise time, peak heart rate, and peak SBP in TTS patients vs. controls, but TTS patients had higher LV volumes, lower exercise LVEF (70 ± 10% vs. 78 ± 7%; P = 0.001), ΔLVEF (4 ± 8% vs. 12 ± 5%; P < 0.001), and WMSI (1.4 ± 0.4 vs. 1 ± 0; P < 0.001) compared with controls. Twenty TTS patients had clear exercise-induced wall motion abnormalities, mainly involving the apex or more globally, with a mean ΔLVEF of 1% compared with 12% in controls. Among the other 10 TTS patients, the ΔLVEF was 10%. Symptomatic patients with previous TTS have a blunted contractile response to exercise. The therapeutic and prognostic implications of these findings need further investigation.

P1497Reversible exercise-induced left ventricular dysfunction in symptomatic patients with previous Takotsubo syndrome - Insights from exercise echocardiography

Abstract Introduction Takotsubo syndrome (TTS) is an acute heart failure syndrome usually associated with rapid and spontaneous recovery of left ventricular (LV) function. However, approximately 10% of patients have persistent symptoms and seek further medical advice. Purpose To determine the cardiovascular haemodynamic and LV contractile response to exercise in these TTS survivors with ongoing symptoms. Methods This was a case-control study of 20 symptomatic patients with previous TTS referred for treadmill exercise echocardiography (EE), and 20 age-, sex- and ethnicity-matched control subjects with normal treadmill EE. Among the TTS group, EE was performed at a median of 8 months (mean 17±21 months) following the index event. Demographic characteristics, resting and EE data were collected. LV ejection fraction (EF) was measured at rest and peak stress. Global longitudinal and circumferential strain (GLS, GCS) were measured at rest. Results All 20 TTS patients were Caucasian postmenopausal females (mean age 63.5±6.6 years). There were no significant differences in body mass index (BMI), resting heart rate (HR) and the prevalence of cardiovascular risk factors compared to controls. Resting systolic and diastolic blood pressure (SBP, DBP) were higher in TTS patients (144±17 mmHg versus 128±18 mmHg, and 81±10 mmHg versus 74±9 mmHg, respectively). A comparative analysis of the resting and stress echo data is given in Table 1. The stress echo data showed similar exercise time and peak HR, but higher peak SBP in TTS patients. TTS patients had blunted contractile response to exercise with lower peak LVEF, ΔLVEF (exercise minus resting EF) and peak wall motion score index (WMSI) compared to controls. Among the 20 TTS patients, 12 had exercise-induced wall motion abnormalities: 6 involved the apical segments and 6 developed global dysfunction. In these 12 patients, the mean ΔLVEF was reduced (4%). In the other 8 patients, the ΔLVEF was 16% and pooled the TTS cohort had blunted contractile response with exercise compared to controls (ΔLVEF 8% vs. 19% in the control group, p=0.001). Table 1 Conclusions Our study shows that symptomatic patients with previous TTS have a blunted contractile response to exercise manifest as reversible apical or global LV dysfunction. These findings might indicate the need for treatment. Further systematic investigation of the therapeutic and prognostic implications of this reversible exercise-induced myocardial dysfunction is needed.

Lung morphology and surfactant function in cardiogenic pulmonary edema: a narrative review.

The conventional analysis of acute cardiogenic pulmonary edema involves the development of high pulmonary capillary pressures resulting in hydrostatic gradients for fluid flux out of capillaries into the interstitial space and alveolar spaces. However, some patients respond poorly to diuretic management. The PubMed database was searched to identify experimental studies on pulmonary edema in animals, experimental studies on surfactant function, including patients with pulmonary edema, and clinical studies reporting barrier dysfunction and/or injury in patients with acute pulmonary edema. Studies with animal models demonstrate that high capillary pressures can cause barrier disruption in alveolar capillary units which increases permeability and the transfer of fluid and protein into lung parenchyma. Fluid in alveolar spaces alters surfactant function which increases fluid flux out of capillaries into the lung parenchyma secondary to larger transcapillary hydrostatic gradients. Patients with acute cardiogenic pulmonary edema have increased levels of surfactant protein B in their plasma which reflect barrier disruption and increased levels of tumor necrosis factor alpha which reflect acute tissue injury. Increased surfactant protein B plasma levels are associated with abnormal gas exchange in patients with chronic heart failure. Patients with exercise-induced left ventricular dysfunction have increased levels of surfactant protein B after short periods of exercise. Pathology studies in patients with chronic heart failure have found increased connective tissue in alveolar capillary units and increased numbers of type II alveolar cells, and these changes represent an adaptive response in these patients. Clinicians need to consider the possibility of barrier dysfunction and disruption in patients with both acute and chronic pulmonary edema and understand that diuresis may have a limited effect on symptoms in some patients.

Prevalence and determinants of exercise-induced left ventricular dysfunction in patients with coronary artery disease.

The phenomenon of exercise-induced left ventricular dysfunction (LVD) is incompletely understood. Better understanding of its prevalence and determinants might help to address the current potential oversimplification of the relation between physical activity and cardiac health in patients with coronary artery disease (CAD). We prospectively assessed the prevalence and determinants of exercise-induced LVD in patients with stable CAD and normal LV function at rest undergoing bicycle rest/stress myocardial perfusion imaging single-photon emission computed tomography (MPI-SPECT). Exercise-induced LVD was defined as a relevant (5% or more) drop in left ventricular ejection fraction after maximal exercise. High-sensitivity cardiac troponin I/T (Hs-cTnI/T) and N-terminal probrain natriuretic peptide (NT-proBNP) concentrations were measured before exercise to quantify cardiomyocyte injury and hemodynamic cardiac stress, respectively. Among 317 patients, exercise-induced LVD was present in 83 (26%) patients. Exercise-induced LVD was associated with the extent of exercise-inducible myocardial ischaemia as well as transient ischaemic dilatation. Still, 43% of patients developing exercise-induced LVD did not have functionally relevant CAD. Neither baseline characteristics, nor the quantification of the extent of cardiomyocyte injury and hemodynamic cardiac stress using hs-cTnI/T and NT-proBNP concentrations, respectively, allowed predicting exercise-induced LVD. One out of four patients with stable CAD develops exercise-induced LVD after bicycle exercise test. While the extent of exercise-inducible myocardial ischaemia is a predictor, other still unrecognized mechanisms also seem to play a major role, as nearly half of all patients with exercise-induced LVD do not have functionally relevant CAD.

0251: Prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive Algerian patients without coronary artery disease

We sought to assess the prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive Algerian patients with normal resting echocardiography and absence of coronary artery disease. From our database of patients (military hospitals of Algeria) referred for treadmill exercise echocardiography, we identified 91 hypertensive patients with preserved resting left ventricular ejection fraction (>50%), no evidence of structural heart disease, and absence of coronary artery disease on angiography. Overall, 38 patients developed exercise-induced left ventricular systolic dysfunction (defined as a decrease in left ventricular ejection fraction below 50% at peak exercise) and 53 exhibited a normal left ventricular ejection fraction response to exercise. The mean follow-up was 6.1 (3.7) years. End points were all-cause mortality, cardiac death, heart failure, and the composite event of cardiac death or heart failure. Patients who developed exercise-induced left ventricular systolic dysfunction were at higher risk of death from any cause (hazard ratio=3.4; 95% confidence interval, 1.1-10.3), cardiac death (hazard ratio=5.6; 95% CI, 1.1-29.4), heart failure (hazard ratio=8.9; 95% confidence interval, 1.8-44.2), and the composite end point (hazard ratio=5.7; 95% confidence interval, 1.7-19.0). In the multivariate analysis, exercise-induced left ventricular systolic dysfunction remained an independent predictor of both heart failure (hazard ratio=6.9; 95% CI, 1.3-37.4) and the composite event of cardiac death or heart failure (hazard ratio=4.5; 95% confidence interval, 1.2-16.0). In hypertensive Algerian patients patients with preserved resting left ventricular ejection fraction and absence of coronary artery disease, exercise-induced left ventricular systolic dysfunction is a strong predictor of cardiac events and may represent early hypertensive heart disease.

Prognostic Value of Exercise-induced Left Ventricular Systolic Dysfunction in Hypertensive Patients Without Coronary Artery Disease

Introduction and objectivesWe sought to assess the prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients with normal resting echocardiography and absence of coronary artery disease. MethodsFrom our database of patients referred for treadmill exercise echocardiography, we identified 93 hypertensive patients with preserved resting left ventricular ejection fraction (≥ 50%), no evidence of structural heart disease, and absence of coronary artery disease on angiography. Overall, 39 patients developed exercise-induced left ventricular systolic dysfunction (defined as a decrease in left ventricular ejection fraction below 50% at peak exercise) and 54 exhibited a normal left ventricular ejection fraction response to exercise. The mean follow-up was 6.1 (3.7) years. End points were all-cause mortality, cardiac death, heart failure, and the composite event of cardiac death or heart failure. ResultsPatients who developed exercise-induced left ventricular systolic dysfunction were at higher risk of death from any cause (hazard ratio=3.4; 95% confidence interval, 1.1-10.3), cardiac death (hazard ratio=5.6; 95%CI, 1.1-29.4), heart failure (hazard ratio=8.9; 95% confidence interval, 1.8-44.2), and the composite end point (hazard ratio=5.7; 95% confidence interval, 1.7-19.0). In the multivariate analysis, exercise-induced left ventricular systolic dysfunction remained an independent predictor of both heart failure (hazard ratio=6.9; 95% CI, 1.3-37.4) and the composite event of cardiac death or heart failure (hazard ratio=4.5; 95% confidence interval, 1.2-16.0). ConclusionsIn hypertensive patients with preserved resting left ventricular ejection fraction and absence of coronary artery disease, exercise-induced left ventricular systolic dysfunction is a strong predictor of cardiac events and may represent early hypertensive heart disease.

Valor pronóstico de la disfunción ventricular izquierda inducida por el ejercicio en pacientes hipertensos sin enfermedad arterial coronaria

Introduction and objectivesWe sought to assess the prognostic value of exercise-induced left ventricular systolic dysfunction in hypertensive patients with normal resting echocardiography and absence of coronary artery disease. MethodsFrom our database of patients referred for treadmill exercise echocardiography, we identified 93 hypertensive patients with preserved resting left ventricular ejection fraction (≥ 50%), no evidence of structural heart disease, and absence of coronary artery disease on angiography. Overall, 39 patients developed exercise-induced left ventricular systolic dysfunction (defined as a decrease in left ventricular ejection fraction below 50% at peak exercise) and 54 exhibited a normal left ventricular ejection fraction response to exercise. The mean follow-up was 6.1 (3.7) years. End points were all-cause mortality, cardiac death, heart failure, and the composite event of cardiac death or heart failure. ResultsPatients who developed exercise-induced left ventricular systolic dysfunction were at higher risk of death from any cause (hazard ratio=3.4; 95% confidence interval, 1.1-10.3), cardiac death (hazard ratio=5.6; 95%CI, 1.1-29.4), heart failure (hazard ratio=8.9; 95% confidence interval, 1.8-44.2), and the composite end point (hazard ratio=5.7; 95% confidence interval, 1.7-19.0). In the multivariate analysis, exercise-induced left ventricular systolic dysfunction remained an independent predictor of both heart failure (hazard ratio=6.9; 95% CI, 1.3-37.4) and the composite event of cardiac death or heart failure (hazard ratio=4.5; 95% confidence interval, 1.2-16.0). ConclusionsIn hypertensive patients with preserved resting left ventricular ejection fraction and absence of coronary artery disease, exercise-induced left ventricular systolic dysfunction is a strong predictor of cardiac events and may represent early hypertensive heart disease.Full English text available from: www.revespcardiol.org/en

Cardiac resynchronization therapy for exercise-induced left ventricular dysfunction in the setting of left bundle branch block: A case report and review of the literature

Exercise-induced dyspnea is one of the most common symptoms that cause a patient to see a physician and a broad differential diagnosis is required. In this case report, we describe a patient with this complaint who had a left bundle branch block and preserved left ventricular function at rest. On stress echocardiography, she had significant exercise-induced left ventricular dysfunction and associated mitral regurgitation but a coronary angiogram demonstrated normal coronary arteries. Both of the echocardiographic findings, as well as her symptoms, improved with the placement of a bi-ventricular pacemaker. A brief review of the literature on cardiac resynchronization therapy for indications beyond the current guidelines is also provided.

Assessment of Pulmonary Arterial Pressure During Exercise in Collagen Vascular Disease: Echocardiography vs Right-Sided Heart Catheterization

This study compared the results of exercise Doppler echocardiography (EDE) with right-sided heart catheterization (RHC) and evaluated the combination of EDE and cardiopulmonary exercise testing (CPET) as a screening method for early pulmonary vasculopathy in patients with connective tissue disease. Patients (N = 52) with connective tissue disease (predominantly systemic sclerosis) and without known pulmonary arterial hypertension underwent both EDE and CPET. If systolic pulmonary arterial pressure (SPAP) was > 40 mm Hg during exercise or peak oxygen uptake (Vo(2)) was < 75% predicted, RHC was suggested. EDE showed an SPAP > 40 mm Hg during exercise in 26/52 patients. Additionally, CPET showed a peak Vo(2) < 75% predicted in 10/26 patients with SPAP <or= 40 mm Hg upon exercise. Accordingly, RHC was suggested to 36 patients. RHC was performed in 28 of these patients, revealing SPAP > 40 mm Hg in 25 patients (n = 1 at rest, n = 24 during exercise). SPAP values assessed by EDE showed no significant difference vs RHC at rest, 25 W, 50 W, and maximal exercise (difference [95% CI]: 0.3 [-2.7; 3.2], -1.3 [-7.1; 4.4], 0.9 [-7.7; 5.9], and -5.6 [-13.5; 2.2] mm Hg). Eight patients with exercise SPAP > 40 mm Hg had an exercise pulmonary arterial wedge pressure > 20 mm Hg, suggesting exercise-induced left ventricular diastolic dysfunction not detectable by EDE. EDE appears to be a reasonable noninvasive method to detect SPAP increase during exercise in connective tissue disease. In combination with CPET, it may be a useful screening tool for early pulmonary vasculopathy, although RHC remains the gold standard for hemodynamic assessment. clinicaltrials.gov; Identifier: NCT00609349 (Early Recognition of Pulmonary Arterial Hypertension).

Exercise-Induced Left Ventricular Systolic Dysfunction in Women Heterozygous for Dystrophinopathy

Mutations in the X-linked gene encoding dystrophin cause skeletal and cardiac muscle diseases in men. Female "carriers" also can develop overt disease. The purpose of this study was to ascertain the prevalence of cardiac contractile abnormalities in dystrophinopathy carriers. Twenty-four dystrophinopathy heterozygotes and 24 normal women each underwent standard exercise stress echocardiography. Heterozygotes demonstrated mildly lower left ventricular ejection fractions (LVEFs) at rest compared with controls (0.56 + or - 0.10 vs 0.62 + or - 0.07, P = .02). After exercise, the mean LVEF fell to 0.53 + or - 0.14 in heterozygotes but rose to 0.73 + or - 0.07 in controls (P < .001). Twenty-one of 24 dystrophinopathy heterozygotes demonstrated > or = 1 of the following: abnormal resting LVEF, abnormal LVEF response to exercise, or exercise-induced wall motion abnormality. Women heterozygous for dystrophinopathy demonstrate significant left ventricular systolic dysfunction, which is unmasked by exercise. This finding has mechanistic implications for both inherited and acquired cardiac disease states.

Cardiopulmonary Exercise Testing with Right-heart Catheterization in Patients with Systemic Sclerosis

To examine the role of cardiopulmonary exercise testing with right-heart catheterization (CPET/RHC) in patients with systemic sclerosis (SSc) with potentially multifactorial exertional limitation. This was a single-center retrospective cohort study of patients with SSc referred for CPET/RHC. A total of 19 patients with SSc [subtypes: 10 limited, 5 diffuse, 1 systemic lupus erythematosus (SLE)/SSc overlap, and 3 with no subtype specified in the medical record] underwent CPET/RHC testing from February 2003 to February 2008. Of these patients, the primary limitations to exercise were found to be ventilatory (n = 6), deconditioning/cardiovascular (n = 6), pulmonary vascular (PVL; n = 3), and exercise-induced left ventricular diastolic dysfunction (exercise-LVDD; n = 4). No prior physical examination, pulmonary function test, imaging, or echocardiographic data reliably predicted the etiology of exercise limitation determined by CPET/RHC. Vital capacity and ventilatory equivalent for CO(2) did not differ during CPET testing between PVL and exercise-LVDD, limiting the utility of CPET alone for discriminating these etiologies of dyspnea. Exercise alveolar-arterial oxygen gradient was elevated in subjects shown to have PVL [median 48 mm Hg (interquartile range 45.3, 62.0)] compared to those with exercise-LVDD [26.0 (IQR 10.6, 36.0)] and deconditioning [13.9 (IQR 4.0, 16.4); p = 0.02]. Major therapeutic changes occurred in 11/19 (58%) subjects after CPET/RHC testing. CPET/RHC testing in subjects with SSc and potentially multifactorial dyspnea adds potentially useful diagnostic information unavailable from noninvasive testing.

Use of Bicycle Exercise Echocardiography for Unexplained Exertional Dyspnea

Unexplained exertional dyspnea is a common and perplexing clinical problem. Myocardial ischemia and left ventricular systolic dysfunction are important cardiac causes, but are often not detected in these patients. Recently, exercise-induced left ventricular diastolic dysfunction and exercised-induced pulmonary hypertension have emerged as common alternative mechanisms. While conventional exercise treadmill echocardiography effectively diagnoses left ventricular systolic dysfunction and myocardial ischemia, it has limited ability to detect exercise-induced diastolic dysfunction or pulmonary hypertension. The latest advances in exercise echocardiography, including utilization of tissue Doppler imaging and harmonic imaging, make noninvasive evaluation of both conventional and alternative cardiac causes of exertional dyspnea possible. These advancements, when coupled with newly designed supine exercise platforms for bicycle exercise echocardiography (BE), facilitate the detection of exercise-induced diastolic dysfunction and pulmonary hypertension. Moreover, BE using supine ergometry additionally permits the dynamic evaluation of valvular function and interatrial shunting and detection of pulmonary arteriovenous fistula, uncommon but important causes of unexplained exertional dyspnea. Therefore, we propose that because of its superior diagnostic capabilities, BE should be included as part of a comprehensive cardiac evaluation of patients with unexplained exertional dyspnea.

The utility of cardiopulmonary exercise testing in the assessment of suspected microvascular ischemia

Evidence demonstrating the potential value of cardiopulmonary exercise testing (CPET) to accurately detect myocardial ischemia secondary to macro-vascular disease is beginning to emerge. Despite distinct mechanisms mediating ischemia in micro-vascular and macrovascular coronary artery disease (CAD), the net physiologic effect of exercise-induced left ventricular (LV) dysfunction is common to both. The abnormal physiologic response to CPET may, therefore, be similar in patients with macro- and micro-vascular ischemia. The following case report describes the CPET abnormalities in a patient with suspected microvascular CAD and the subsequent improvement in LV function following three weeks of medical therapy with the anti-ischemic drug ranolazine.

Influence of physical training on cardiac performance in patients with coronary artery disease and exercise-induced left ventricular dysfunction

Objective — The aim of the study was to assess the influence of physical training on systolic and diastolic left ventricular (LV) function using seismocardiography (SCG) and its relationship to the exercise capacity in CAD patients with exercise-induced LV dysfunction.Methods and results — Eighty men aged 52.5 ± 7.5 y with stable CAD were assigned to either a control group (CG, n = 40) or a training group (TG, n = 40).TG patients underwent a 4.5-month training programme (TP). Before and at the end of the study all patients underwent a cardiopulmonary test (CPET) and SCG. After TP the following CPET parameters improved significantly: duration (776 ± 120 vs. 879 ± 89 s, P < 0.001), METs (8 ± 2 vs. 10 ± 1, P < 0.01), maxVO2 (22 ± 4 vs. 25 ± 3 ml/kg/min, P < 0.001). During SCG performed before (SCGREST) and immediately after each CPET (SCGCPET) the following variables improved significantly, but only in TG patients: the pre-ejection period (PEP; 126 ± 15 vs. 119 ± 14, P < 0.05 ms), PEP/LVET ratio (PEP/LV ejection time, ms; 0.42 ± 0.08 vs. 0.38 ± 0.06, P < 0.05).There was a negative correlation between training-induced changes in maxVO2 and PEPCPET (r =-0.4, P = 0.01) and PEP/LVETCPET (r =-0.52, P = 0.001), and a positive correlation between maxVO2 and LVETCPET (r = 0.51, P = 0.01). After TP, there was also a negative correlation between maxVO2 and isovolumetric relaxation time (ms;r =-0.46, P = 0.01).Conclusions — The training programme resulted in a significant improvement in the physical capacity and cardiac performance in CAD patients with exercise-induced left ventricular dysfunction.An improvement of systolic left ventricular function suggested an increase in exercise capacity.

Cumulative exercise-induced left ventricular systolic and diastolic dysfunction in hypertrophic cardiomyopathy

The phenomenon of cumulative exercise-induced left ventricular function impairment was studied in 40 patients with non-obstructive hypertrophic cardiomyopathy with resting normal left ventricular function and no increase in ejection fraction on exercise. All patients underwent two symptom-limited exercise tests one-hour apart. Cumulative myocardial dysfunction was seen in 13 patients (group I) but not in the remaining 27 patients (group II). During follow-up, group I showed more commonly than group II a deterioration in symptoms (67% vs 22%, P = 0.025) and left ventricular function (50% vs 9%, P = 0.019). In conclusion, cumulative exercise-induced myocardial dysfunction can occur in hypertrophic cardiomyopathy and may be associated with clinical deterioration and worse outcome.

CIRCULATING SURFACTANT PROTEIN‐B LEVELS INCREASE ACUTELY IN RESPONSE TO EXERCISE‐INDUCED LEFT VENTRICULAR DYSFUNCTION

1. As a result of its enormous surface area and necessary thinness for gas exchange, the alveolocapillary barrier is vulnerable to mechanical disruption from raised pulmonary microvascular pressure (Pmv). 2. Because surfactant protein-B (SP-B) leaks into the blood stream from the alveoli in response to alveolocapillary barrier damage and exercise leads to increased Pmv, we sought to determine whether exercise results in increased plasma SP-B. Moreover, in the setting of exercise-induced left ventricular dysfunction, the consequent increase in left heart filling pressure and, therefore, P(mv) would be expected to further increase plasma SP-B levels. 3. Twenty consecutive subjects referred for treadmill exercise stress echocardiography (ESE) had venous blood sampled immediately before and after ESE for batch atrial natriuretic peptide (ANP) and SP-B assay. Echocardiographic measures of pulmonary haemodynamics (pulmonary artery flow acceleration time (pafAT) and right ventricular outflow tract velocity time integral (rVTI)) were also taken pre- and post-exercise. 4. Although circulating ANP levels increased following exercise (P < 0.001), there was no change in circulating SP-B levels in the entire cohort. 5. Ten subjects had a positive ESE for ventricular dysfunction. Although circulating ANP was increased post-exercise in both the negative and positive ESE groups (P < 0.05 and P < 0.01, respectively), circulating SP-B only increased post-exercise in the positive ESE group (P < 0.05). Echocardiographic parameters supported an increment in P(mv) in the cohort with exercise-induced left ventricular dysfunction because this group had an increase in pafAT (P < 0.05; reflecting pulmonary artery pressure) and no change in rVTI. 6. Physical exertion associated with a Bruce protocol ESE is insufficient to increase circulating SP-B, despite evidence of increased left atrial and pulmonary vascular pressure. However, in the setting of exercise-induced myocardial dysfunction, there is a detectable increase in circulating SP-B. 7. The exaggerated increase in pulmonary vascular pressure in exercise-induced myocardial dysfunction may result in increased SP-B leakage from the alveoli into the circulation by altering the integrity of the alveolocapillary barrier to protein.

Transient cavity dilation (TCD) and stress-induced stunning assessed by pharmacologic stress gated Tl-201 myocardial SPECT

Background: Transient left ventricular (LV) cavity dilation with apical thinning is frequently seen on ungated stress-rest myocardial perfusion SPECT with exercise stress. Transient LV dilation has been proposed as a marker of exercise-induced left ventricular dysfunction, i.e., stunning, which has been found in patients with coronary artery disease. But patients without coronary artery disease show transient LV dilation and apical thinning pattern, which could be one of the causes of false-positive myocardial SPECT. Purpose: We investigated the incidence of TCD in Tl-201 SPECT performed immediately after pharmacologic stress and the relationship between the TCD detected visually on ungated perfusion SPECT and LV function and volume measured by post-stress and rest gated Tl-201 SPECT. We also determined its relations to coronary artery disease by comparing ischemic group and low-risk normal perfusion group. Methods: Post-stress and rest gated Tl-201 SPECT with adenosine stress were performed with 174 patients (men 95 and 79 women, mean age 62). Rotating dual-head gamma camera was used through a 180° arc using 32 projections, 50s per projection. Perfusion defect and the pattern of TCD with apical thinning were detected visually on ungated SPECT. LV volume and ejection fraction (EF) of both stress and rest were calculated using an automatic algorithm-4DMSPECT. The poststress and rest ratios were determined for both end-diastolic (EDV) and end-systolic (ESV) volume. Results: Ninety-one patients (52.3%) showed normal perfusion, 63(36.2%) reversible defects and 20(11.5%) had fixed defects. TCD with apical thinning was detected in 68(74.7%) out of 91 patients with normal perfusion. In normal perfusion group, the EF change and stress/rest ratio of EDV and ESV were significantly different between patients with TCD and apical thinning (mean±SD, SEE, group A: EF change=0.86±8.3%, 0.92, s/rEDV=1.09±0.23, 0.02, s/rESV=1.28±1.32, 1.14) and those without TCD(group B: EF change=4.9±5.3%, 1.68, s/rEDV=0.93±0.11, 0.03, s/rESV =0.81±0.17, 0.05) (p<0.05). For group A, EDV and ESV measured by stress (66.5±25.8, 23.1±15.1) and rest (61.8±25.7, 20.9±14.6) were significantly different (p<0.01) but EF showed no difference (67.8±9.8, 68.7±9.6,p=0.37). There were no statistical differences of EF change, s/rEDV, s/rESV among patients with normal perfusion (0.36±8.15,1.08±0.23,1.23±1.26), reversible (2.25±9.37, 1.08±0.21, 1.28±0.95), and fixed defect (1.00±8.59, 1.02±0.13,1.07±0.25). Conclusion: TCD with apical thinning seen on ungated perfusion SPECT suggests systolic and diastolic LV dilation by pharmacological stress without change of LV global function, which could be noted frequently in normal myocardial perfusion SPECT and not related to stunning or existence of perfusion defect.

Early myocardial dysfunction in the diabetic heart: current research and clinical applications

Patients with diabetes mellitus have a high incidence of heart failure, which contributes significantly to their increased cardiovascular morbidity and mortality. One of the major complications of diabetes is the development of cardiomyopathy, a condition characterized by defects of contractile function in the absence of significant coronary artery disease or systemic hypertension. Experimental data in animal models show that contractile depression begins as early as 1 week after induction of diabetes, and the dysfunction is related to an isomyosin distribution shift from V 1 with high adenosine triphosphatase (ATPase) to V 3 with low ATPase activity. Moreover, diabetes is associated with an increased or poorly regulated rate of amino acid catabolism at the cardiac level. Abnormal responses to acute left ventricular (LV) overload induced by exercise (isometric or isotonic) have been demonstrated in patients with diabetes. Impaired augmentation of LV ejection fraction occurs in up to 40% of patients with diabetes. Analysis of the LV afterload-pump function (LV circumferential wall stress-ejection fraction) relationship shows that defective contractile recruitment is the main cause of this anomaly. Exercise-induced LV dysfunction may be the first manifestation of cardiac involvement in patients with diabetes. Increasing the supply of amino acids in addition to conventional therapy significantly attenuates this phenomenon. Although the precise underlying pathophysiologic mechanism is not completely known, these observations may eventually be important in designing an optimal dietary or supplemental approach for patients with diabetes in order to prevent progressive myocardial dysfunction.

Early myocardial dysfunction in the diabetic heart: current research and clinical applications

Patients with diabetes mellitus have a high incidence of heart failure, which contributes significantly to their increased cardiovascular morbidity and mortality. One of the major complications of diabetes is the development of cardiomyopathy, a condition characterized by defects of contractile function in the absence of significant coronary artery disease or systemic hypertension. Experimental data in animal models show that contractile depression begins as early as 1 week after induction of diabetes, and the dysfunction is related to an isomyosin distribution shift from V1 with high adenosine triphosphatase (ATPase) to V3 with low ATPase activity. Moreover, diabetes is associated with an increased or poorly regulated rate of amino acid catabolism at the cardiac level. Abnormal responses to acute left ventricular (LV) overload induced by exercise (isometric or isotonic) have been demonstrated in patients with diabetes. Impaired augmentation of LV ejection fraction occurs in up to 40% of patients with diabetes. Analysis of the LV afterload-pump function (LV circumferential wall stress-ejection fraction) relationship shows that defective contractile recruitment is the main cause of this anomaly. Exercise-induced LV dysfunction may be the first manifestation of cardiac involvement in patients with diabetes. Increasing the supply of amino acids in addition to conventional therapy significantly attenuates this phenomenon. Although the precise underlying pathophysiologic mechanism is not completely known, these observations may eventually be important in designing an optimal dietary or supplemental approach for patients with diabetes in order to prevent progressive myocardial dysfunction.