Selenium Deficiency as a Risk Factor for Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a multifactorial disease. Although the specific aetiology and pathogenesis of PPCM are unknown, several hypotheses have been proposed, including selenium deficiency. However, the risk of PPCM from selenium deficiency was not previously quantified. This posthoc analysis of peripartum cardiomyopathy in Nigeria (PEACE) registry data aimed to determine if selenium deficiency is an independent risk factor for PPCM. METHODS: Apparently healthy women who delivered within the previous 8 weeks and PPCM patients in Kano, Nigeria, were compared for selenium deficiency (<70µg/L) and other relevant socio-demographic and clinical characteristics. Selenium level was measured at recruitment for each subject. Independent predictors of PPCM were determined using logistic regression models. RESULTS: 159 PPCM patients and 90 age-matched controls were consecutively recruited. 84.9% of the patients and 3.3% of controls had selenium deficiency. Selenium deficiency independently increased the odds for PPCM by 167-fold while both unemployment and lack of formal education independently increased the odds by 3.4-fold. CONCLUSION: Selenium deficiency was highly prevalent among PPCM patients in Kano, Nigeria, and significantly increased the odds for PPCM. These results could justify screening of women in their reproductive years for selenium deficiency, particularly those living in regions with high incidence of PPCM. The results also call for the setting up of a definitive clinical trial of selenium supplementation in PPCM patients with selenium deficiency, to further define its benefits in the treatment of PPCM.

CONTEXTE: La cardiomyopathie péripartum (CMPP) est une maladie multifactorielle. Bien que l'étiologie spécifique et la pathogenèse de la CMPP soient inconnues, plusieurs hypothèses ont été proposées, notamment la carence en sélénium. Cependant, le risque de CMPP lié à la carence en sélénium n'a pas été précédemment quantifié. Cette analyse post-hoc des données du registre de la cardiomyopathie péripartum au Nigéria (PEACE) visait à déterminer si la carence en sélénium est un facteur de risque indépendant de la CMPP. MÉTHODES: Des femmes apparemment en bonne santé ayant accouché dans les 8 semaines précédentes et des patientes atteintes de CMPP à Kano, au Nigéria, ont été comparées pour la carence en sélénium (<70µg/L) et d'autres caractéristiques socio-démographiques et cliniques pertinentes. Le taux de sélénium a été mesuré au recrutement pour chaque sujet. Les prédicteurs indépendants de la CMPP ont été déterminés à l'aide de modèles de régression logistique. RÉSULTATS: 159 patientes atteintes de CMPP et 90 témoins appariés selon l'âge ont été recrutés consécutivement. 84,9% des patientes et 3,3% des témoins présentaient une carence en sélénium. La carence en sélénium augmentait indépendamment les chances de CMPP de 167 fois, tandis que le chômage et le manque d'éducation formelle augmentaient indépendamment les chances de 3,4 fois. CONCLUSION: La carence en sélénium était très répandue parmi les patientes atteintes de CMPP à Kano, au Nigéria, et augmentait significativement les chances de CMPP. Ces résultats pourraient justifier le dépistage de la carence en sélénium chez les femmes en âge de procréer, en particulier celles vivant dans des régions à forte incidence de CMPP. Les résultats appellent également à la mise en place d'un essai clinique définitif sur la supplémentation en sélénium chez les patientes atteintes de CMPP présentant une carence en sélénium, afin de définir davantage ses avantages dans le traitement de la CMPP. MOTS-CLÉS: Cardiomyopathie Péripartum; Carence en Sélénium; Facteur de Risque.

Disease progression in cardiac morphology and function in heart failure: ATTR cardiac amyloidosis versus hypertensive left ventricular hypertrophy.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is today more frequently recognized but the rate of progression of cardiac dysfunction is not well established. The aim of this study is to investigate the nature of cardiac structure and function changes, over time, in a retrospective cohort of ATTR-CA patients. METHODS: Fifty-one patients with ATTR-CA (mean age 78 ± 7 years, 30 females) were compared with 20 patients with heart failure but no amyloidosis (HFnCA) (mean age 76 ± 7 years, 5 females), all with septal thickness > = 14 mm. All patients underwent DPD scintigraphy and an echocardiogram (Echo 2) which was compared with a previous echocardiographic examination (Echo 1), performed at least 3 years before. RESULTS: Over the follow-up period, the interventricular septal thickness (IVST) and relative wall thickness (RWT) in ATTR-CA increased from 16 (4) to 18 (5) mm and from 0.51 (0.17) to 0.62 (0.21) respectively, p < 0.001 for both, by a mean increase of 0.4 mm/year and 0.03 mm/year, (p = 0.009 and p = 0.002 compared with HFnCA), respectively. RWT > 0.45 (AUC = 0.77) and RELAPS > 2.0 (AUC 0.86) both predicted positive DPD diagnosis for ATTR-CA. CONCLUSION: In ATTR-CA patients, the overtime-increase in RWT and IVST was worse than that seen in patients with heart failure but no cardiac amyloidosis. Also, RWT and relative apical sparing predicted diagnosis of ATTR-CA, thus could strengthen the use of follow-up echocardiographic findings as red flag for the diagnosis of ATTR-CA.

Passive leg-lifting in heart failure patients predicts exercise-induced rise in left ventricular filling pressures.

AIM: The aim of this study was to assess PCWP with passive leg-lifting (PLL) and exercise, in two groups of patients presenting with normal left ventricular ejection fraction (LVEF); one group with elevated NT-proBNP (eBNP), and one with normal NT-proBNP (nBNP) plasma concentration. METHODS AND RESULTS: Fifty-one patients with eBNP (NT-proBNP ≥ 125 ng/l) and LVEF > 50%, were investigated and compared with 34 patients with nBNP (NT-proBNP < 125 ng/l) and LVEF > 50%. Both groups underwent right heart catheterization (RHC) at rest, PLL and exercise. From RHC, mean pulmonary arterial pressure (mPAP), cardiac output (CO), and PCWP were measured. All nBNP patients had PCWP < 15 mmHg at rest, and a PCWP of < 25 mmHg with PLL and during exercise. Patients with eBNP had higher (p < 0.01) resting mPAP, PCWP, and mPAP/CO. These values increased with exercise; however, CO increased less in comparison with nBNP patients (p = 0.001). 20% of patients with eBNP had a PCWP > 15 mmHg at rest, this percentage increased to 47% with PLL and 41% had a PCWP > 25 mmHg during exercise. Of those with PCWP > 25 mmHg during exercise, 91% had a PCWP > 15 mmHg with PLL. A PCWP > 15 mmHg on PLL had a 91% sensitivity and 92% specificity in predicting exercise-induced PCWP of > 25 mmHg. CONCLUSION: In patients presenting with eBNP, PLL can predict which patients will develop elevated PCWP with exercise. These findings highlight the role of stress assessment.

Prevalence and predictors of right ventricular diastolic dysfunction in peripartum cardiomyopathy.

BACKGROUND: This study aimed to assess the prevalence of right ventricular diastolic dysfunction (RVDD) and its potential predictors in peripartum cardiomyopathy (PPCM) patients. METHODS: This was a cross-sectional study carried out in Nigeria. RVDD was defined and graded using Doppler filling and myocardial tissue Doppler velocities obtained at tricuspid annular level. RESULTS: Forty-three subjects with PPCM and mean age of 26.6 ± 7.0 years were recruited over 6 months. RVDD was found in 30 (69.8 %) subjects, of whom 16 (53.3 %) had grade I, 12 (40.0 %) had grade II and 2 (6.7 %) had grade III severity. RV systolic dysfunction (RVSD), defined as RV fractional area change <35 %, was found in 88.4 %, while combined RVSD and RVDD was found in 58.1 % of patients. Subjects with RVDD had significantly higher tricuspid E/e' ratio (5.1 ± 2.8 versus 3.5 ± 1.0, p = 0.012) and prevalence of pulmonary hypertension (76.7 versus 46.2 %; p < 0.05), and lower serum selenium concentration (55.6 ± 12.1 versus 72.5 ± 12.0 µg/L, p = 0.001) than those with preserved RV diastolic function. Regression analyses showed serum selenium [odds ratio (OR) = 1.14; 95 % confidence interval (CI) = 1.0-1.3; p = 0.049] and combined RVSD and pulmonary hypertension (OR = 79.2; CI = 3.9-1593.7; p = 0.004) as the only predictors of RVDD, and serum selenium <70 µg/L increased the odds of RVDD by 6.67-fold (CI = 1.18-37.78; p = 0.032). CONCLUSIONS: Both RVDD and RVSD were common in PPCM patients. Selenium deficiency and combined RVSD and pulmonary hypertension seemed to be the only determinants of RVDD in this small cohort, a finding that needs verification in a larger sample of patients.

Carotid plaque echogenicity predicts cerebrovascular symptoms: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Many reports have shown an association between hypoechoic (echolucent) carotid atherosclerotic plaques and unstable features. In this meta-analysis our aim was to determine the role of carotid plaque echogenicity in predicting future cerebrovascular (CV) symptoms. METHODS: Electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to September 2015 were systematically searched. Studies with ultrasound-based characterization of carotid artery plaque echogenicity and its association with focal neurological symptoms of vascular origin were eligible for analysis. In the meta-analysis, heterogeneity was measured using I(2) statistics and publication bias was evaluated using the Begg-Mazumdar test. In addition several comparisons between subgroups were performed. RESULTS: Of 1387 identified reports, eight studies with asymptomatic patients and three studies with symptomatic patients were meta-analyzed. Pooled analysis showed an association between echolucent carotid plaques and future CV events in asymptomatic patients [relative risk 2.72 (95% confidence interval 1.86-3.96)] and recurrent symptoms in symptomatic patients [relative risk 2.97 (95% confidence interval 1.85-4.78)]. The association was preserved for all stenosis degrees in asymptomatic patients, whilst patients with echolucent plaques and severe stenosis were at higher risk of future events. Also, computer-assisted methods for assessment of carotid plaque echogenicity and studies analyzing ultrasound data collected after the year 2000 showed better prediction. CONCLUSIONS: In asymptomatic and symptomatic patients, analysis of carotid plaque echogenicity could identify those at high risk of CV events.

Coronary artery calcification correlates with the presence and severity of valve calcification.

AIM: To investigate the prevalence of coronary artery calcification (CAC) in symptomatic individuals with CT evidence for left heart valve calcification, aortic valve (AVC), mitral valve (MAC) or both. METHODS: This is a retrospective study of 282 consecutive patients with calcification in either the aortic valve or mitral annulus. Calcium scoring of the coronary artery, aortic and mitral valve was measured using the Agatston score. RESULTS: AVC was more prevalent than MAC (64% vs. 2.5%, p < 0.001), with 34% having both. Absence of CAC was noted in 12.7% of the study population. AVC + CAC were observed in 53.5%, MAC and CAC in 2.1%, and combined AVC, MAC and CAC in 31.6%. The median CAC score was higher in individuals with combined AVC+MAC, followed by those with AVC and lowest was in the MAC group. The majority (40%) of individuals with AVC had CAC score >400, and only in 16% had CAC = 0. The same pattern was more evident in individuals with AVC + MAC, where 70% had CAC score >400 and only 6% had CAC score of 0. These results were irrespective of gender. There was no correlation between AVC and MAC but there was modest correlation between CAC score and AVC score (r = 0.28, p = 0.0001), MAC (r = 0.36, p = 0.0001) and with combined AVC + MAC (r = 0.5, p = 0.0001). AVC score of 262 had a sensitivity of 78% and specificity of 92% for the prediction of presence of CAC. CONCLUSION: The presence and extent of calcification in the aortic valve or/and mitral valves are associated with severe coronary artery calcification.

Severity of aortic stenosis predicts early post-operative normalization of left atrial size and function detected by myocardial strain.

BACKGROUND: Aortic stenosis (AS) causes significant disturbances in left ventricular (LV) and left atrial (LA) function irrespective of the extent of myocardial hypertrophy which associates the increased afterload. We hypothesize that aortic valve replacement (AVR) and removal of LV outflow tract obstruction should result in LA size and function recovery, even partial, and were set to study this in a group of patients with AVR for AS. METHODS: Peak atrial longitudinal strain (PALS) was evaluated in 43 patients with severe isolated AS and normal EF (56.6 ± 3.8%) and no obstructive coronary artery disease candidates for AVR, pre-operatively and then 40 days and 3 months after surgery. Results were compared with those from 34 age- and gender-matched healthy controls. RESULTS: LVEF remained unchanged and LV mass regressed after AVR. Global PALS was reduced pre-operatively and increased 40 days after surgery (p=0.002) and showed only a slight further increase at 3 months follow-up (p<0.0001). Indexed LA volume was increased before surgery, but significantly fell 40 days after surgery (p<0.0001) and showed only a slight further reduction after 3 months (p<0.0001). Trans-aortic mean gradient change after surgery was the only independent predictor of the recovery of LA size and function. CONCLUSIONS: AVR reverses LA abnormalities and regains normal atrial function, a behavior which is directly related to the severity of pre-operative LV outflow tract obstruction. Early identification of LA size enlargement and functional disturbances might contribute to better patient's recruitment for AVR.

Aggressive and diffuse coronary calcification in South Asian angina patients compared to Caucasians with similar risk factors.

BACKGROUND: Ethnic differences in prevalence and severity of coronary artery disease are well established and are usually attributed to risk factors variation. This study investigates the differences in coronary artery narrowing and coronary calcification between two age- and gender-matched cohorts of South Asian and Caucasian symptomatic angina patients. METHODS: We identified 101 symptomatic angina patients of South Asian origin who had undergone CT angiography and calcium scoring, and compared them with 101 age and gender matched Caucasian patients. RESULTS: South Asians had a greater mean number of arterial segments with both obstructive and non-obstructive plaque than Caucasians (p=0.006 and p=0.0003, respectively) and higher prevalence of triple-vessel disease (p=0.0004). Similarly, South Asians had a higher mean CAC score (p<0.0001) and the percentage of South Asians with CAC>0 and in all categories of CAC score 100-1000 were also higher, as was the number of arterial segments with calcified and non-calcified plaque. These results were more marked in patients aged >50 but in those ≤ 50, Caucasians showed a higher mean number of diseased segments (p=0.019), with non-obstructive plaque (p=0.02), possibly suggesting that Caucasians are likely to have more diffuse atherosclerosis at an earlier age. CAC prevalence and severity in this age-group were not significantly different between South Asians and Caucasians. CONCLUSION: Despite similar conventional risk factors for CAD, symptomatic South Asians seem to have more aggressive and diffuse arterial calcification compared to Caucasians. These differences are more profound above the age of 50, suggesting potential genetic or other risk factors yet to be determined.

Mitral annular longitudinal function preservation after mitral valve repair: the MARTE study.

BACKGROUND: In patients with chronic mitral regurgitation (MR), undergoing surgical mitral valve repair, current Guidelines only recommend standard echocardiographic indices i.e. left ventricular (LV) ejection fraction (EF), and LV end-systolic and end-diastolic diameters as preoperative variables. However LV EF is often preserved until advanced stages of the valve disease. Aim of this study was to evaluate changes in LV systolic longitudinal function, 3 months after mitral valve repair in patients with chronic degenerative MR and normal preoperative EF. METHODS: We measured M-mode mitral lateral annulus systolic excursion (MAPSE) and Tissue Doppler (TD) peak systolic annular velocity (S(m)) in 31 patients with moderate to severe MR and normal EF (59.9 ± 4.7%) candidates for mitral valve repair, preoperatively and 3 months after surgery. RESULTS: After mitral valve repair, S(m) increased from 7.8 ± 1.4 to 9.6 ± 2.2 cm/s (p<0.0001) and MAPSE increased from 1.33 ± 0.26 to 1.55 ± 0.25 cm (p=0.0013). EF decreased from 59.9 ± 4.7 to 51.3 ± 5.9% (p<0.0001). As expected, LV diameters and volumes, wall thicknesses, midwall fractional shortening (mFS), and left atrial (LA) size were all reduced after surgery. CONCLUSIONS: This study suggests that assessment of LV long axis systolic velocity and amplitude of excursion by echocardiography is more sensitive than simple determination of EF for revealing the beneficial impact of MR surgery on overall systolic function.

Ventricular dysfunction in type 1 myotonic dystrophy: electrical, mechanical, or both?

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a systemic disease which affects the heart and may be a cause of sudden death. Conduction disturbances are the major cardiac abnormalities seen in this condition. We sought to assess electrical and mechanical cardiac functions to identify abnormalities that might explain sudden cardiac death in DM1. METHODS: Thirty six patients with DM1 and 16 controls were studied using echocardiography including myocardial Doppler. ECG recordings were also obtained. RESULTS: Left ventricular (LV) dimensions were maintained but systolic function was reduced (p<0.001), including stroke volume (p<0.05). LV segmental myocardial isovolumic contraction time was prolonged (p<0.001) and correlated with PR interval (p<0.001). Isovolumic relaxation time was prolonged (p<0.05) and filling time was reduced (p<0.001). LV cavity was significantly asynchronous demonstrated by prolonged total isovolumic time (t-IVT) (p<0.001), high Tei index (p<0.001) and low ejection index (p<0.001). Right ventricular (RV) strain was reduced (p<0.001) as were its systolic and diastolic velocities (p<0.05 for both). 22/36 patients had prolonged LV t-IVT>12.3 s/min (upper 95% normal CI), 13 of whom had PR≥200 ms, 11 had QRS duration>120 ms (5 had combined abnormality) and the remaining 5 had neither. Over the 3 years follow up 10 patients had events, 6 of them cardiac. t-IVT was prolonged in 5/6 patients, PR interval in 4 and QRS duration in one. CONCLUSIONS: In DM1 patients, LV conventional measurements are modestly impaired but cardiac time relations suggest marked asynchronous cavity function. Although our findings were primarily explained on the basis of long PR interval or broad QRS duration a minority presented an evidence for myocardial cause of asynchrony rather than electrical. Early identification of such abnormalities may guide towards a need for additional electrical resynchronization therapy which may improve survival in a way similar to what has been shown in heart failure trials.

Resolution of central sleep apnoea following implantation of a left ventricular assist device.

Central sleep apnoea (CSA) occurs in up to 40% of patients with chronic heart failure (CHF). It is thought to be a consequence of CHF and is associated with an accelerated decline in cardiac function, and increased morbidity and mortality. The optimal treatment of CSA remains unclear. Resolution of CSA has been reported after cardiac transplantation. We report the first case of resolution of CSA 10 months following implantation of a permanent Jarvik 2000 left ventricular assist device (LVAD). The correction of CSA after implantation of the LVAD was associated with improvements in symptoms, exercise capacity, renal function, and increased arterial carbon dioxide levels at rest during wakefulness and also reduction in brain natriuretic peptide.

Left ventricular long axis dysfunction in adults with "corrected" aortic coarctation is related to an older age at intervention and increased aortic stiffness.

OBJECTIVES: This study examined the prevalence of left ventricular (LV) long axis dysfunction (LAD, septal annulus pulsed-wave (PW) tissue Doppler imaging (TDI) early diastolic velocity < or =8 cm/s) in patients with "corrected" aortic coarctation and its relationship to patient demographics and aortic elastic properties. METHODS: A retrospective study of 80 consecutive patients with "corrected" aortic coarctation (aged 27 (SD 6) years, seven postballoon aortoplasty, 41 poststenting and 32 postsurgical repair) was carried out. Patients' ages at intervention, comorbidities and medications were recorded. The LV long axis motions were recorded by M-mode and PW TDI. Aortic stiffness indices were calculated from the aortic diameters and pulse pressures. RESULTS: Forty-seven patients (59%) had LAD. They were older (28 (5) vs 9 (6) years) at treatment, had stiffer aorta (stiffness index 18.4 (6.0) vs 9.2 (2.3)), thicker LV walls (146.7 (59.7) vs 103.8 (44.9) g/m2), higher wall stress (80 (6) vs 70 (7) 10(3) dynes/cm2), larger left atria (31.7 (4.6) vs 24.5 (5.3) ml/m2) and higher LV filling pressures (p<0.01 for all) compared with those without LAD, despite a similar prevalence of antihypertensive use and bicuspid aortic valves. The age at intervention (OR 2.92, 95% CI 1.29 to 6.60, p<0.01) and aortic stiffness index (OR 1.98, 95% CI 1.41 to 2.79, p<0.001) were the two independent predictors for LAD in patients on multivariate analysis. A cut-off age of > or =25 year at intervention was 89% sensitive and 76% specific in predicting LAD (AUC = 0.90, p<0.001). CONCLUSIONS: LAD is common in adults with aortic coarctation despite apparently successful treatment. Its presence is related to older age at intervention and increased aortic stiffness.

Asynchronous normal regional left ventricular function assessed by speckle tracking echocardiography: appearances can be deceptive.

BACKGROUND: Speckle tracking echocardiography (STE) is an angle independent method with high temporal resolution, which offers quantification of regional left ventricular (LV) wall motion. We studied radial and longitudinal LV wall motion by STE in healthy subjects with normal wall motion analysis (WMA) by eye-balling. MATERIALS AND METHODS: Eighteen healthy subjects were studied. We acquired parasternal short and apical long axis projections to determine the basal, mid and apical radial and longitudinal functions. At each level we measured; (I) radial and longitudinal peak displacement and displacement at aortic valve closure (AVC) and (II) the time interval from the Q-wave to the AVC and peak displacement. RESULTS: WMA indicated normal wall motion in all subjects. The mean peak radial displacement varied in different segments (range 3.9-9.8 mm) with highest values in the mid-level (6.9+/-1.5 mm), compared to basal level (5.9+/-1.0 mm, p<0.01) and apical level (5.4+/-1.0 mm, p<0.001). The time from Q-wave to AVC was 393 ms and in 89% of the analysed segments peak radial displacement occurred after AVC, thus mean peak radial displacement occurred 60 ms after AVC. The peak longitudinal amplitude was more synchronous with respect to AVC and with the highest amplitudes found in the two basal segments. CONCLUSIONS: In normal LV function, significant differences in peak displacement exist between segments at various LV levels using STE. In addition, in early diastole, significant discrepancy occurs between radial and longitudinal time of peak displacement, suggesting a shape change. Finally, while radial displacement was highest at mid-cavity level longitudinal displacement was highest at basal level.

Beyond dyssynchrony in cardiac resynchronisation therapy.

Cardiac resynchronisation therapy (CRT) in the form of biventricular pacing has emerged as a therapeutic option for patients with refractory heart failure. Patient selection and optimisation for CRT is based on the measurement of electromechanical ventricular dyssynchrony by electrocardiogram and echocardiographic techniques. The final common pathway for raising cardiac output on exertion is to minimise isovolumic time and maximise useful diastolic filling time, but correction of dyssynchrony alone may not lead to global improvement in about one-third of patients. Insights into pressure relations and abnormal timing, as well as clinical management, may hold the key to optimum outcome.

Age dependency in the timing of mitral annular motion in relation to ventricular filling in healthy subjects: Umea General Population Heart Study.

AIMS: Peak left ventricular (LV) relaxation normally precedes peak filling (E), which supports the hypothesis that LV suction contributes to early-diastolic filling. The significance of similar temporal discordance in late diastole has previously not been studied. We describe the time relationships between mitral annular motion and LV filling in early and late diastole and examine the effect of normal ageing on these time intervals. METHODS AND RESULTS: A total of 128 healthy subjects aged 25-88 years were studied. Transmitral and pulmonary venous flow reversals (Ar) were recorded by Doppler echocardiography. Mitral annular diastolic displacement-early (E(m)) and late (A(m))-were recorded by Doppler tissue imaging. With reference to electrocardiographic R and P-waves, the following measurements were made: R to peak E-wave (R-E) and E(m) (R-E(m)); onset P to peak A-wave (P-pA), A(m) (P-pA(m)), and Ar (P-pAr). The differences between [(R-E) and (R-E(m))] for early-diastolic temporal discordance (EDTD) and [(P-A) and (P-A(m))] for late-diastolic temporal discordance (LDTD) were calculated. Isovolumic relaxation time (IVRT) was also measured. Early-diastolic temporal discordance was approximately 26 ms in all age groups. Late-diastolic temporal discordance, however, was inversely related to age (r = -0.35, P < 0.001) and IVRT (r = -0.34, P < 0.001) and therefore decreased in the elderly vs. young (13 +/- 10 vs. 23 +/- 10 ms; P < 0.001). In multivariate analysis, age failed to predict LDTD in the presence of IVRT. A, A(m), and Ar were simultaneous at onset, and peak A(m) coincided with peak Ar in all age groups (r = 0.97, P < 0.001). No significant differences were noted in the RR intervals. CONCLUSIONS: Sequential prolongation of IVRT with ageing reduces LDTD, thus converging the peaks of A(m), A, and Ar (atrial mechanical alignment)-a potential novel method to identify subjects at increased dependency on atrial contraction for late-diastolic filling.

Instantaneous effects of resynchronisation therapy on exercise performance in heart failure patients: the mechanistic role and predictive power of total isovolumic time.

BACKGROUND: Cardiac resynchronisation therapy improves peak oxygen uptake (peak VO(2)) 3-9 months after device implantation. In chronic heart failure, total isovolumic time (t-IVT) is a major determinant of peak VO(2) and of cardiac output at peak dobutamine stress. In selected patients, resynchronisation can instantaneously shorten t-IVT. We sought to determine the acute effect of resynchronisation on exercise performance and determine, with pharmacological stress echocardiography, the mechanism underlying this effect. METHODS AND RESULTS: Twenty-two patients with resynchronisation were studied within 3 months after device implantation. On a single study day, sequential cardiopulmonary exercise tests were performed during native activation (left bundle branch block) and resynchronisation (atrio-biventricular pacing) in random order. Total-IVT and cardiac output (at rest and peak dobutamine stress) were then measured in each activation mode. Resynchronisation acutely increased peak VO(2) by 1.6 (SD 1.5) ml/kg/min (p<0.001) and shortened peak stress t-IVT by 10 (SD 7) s/min (p<0.001), with the effects in individual patients showing a correlation (r = -0.46, p<0.05). Amongst all measurements during native activation, the best predictor of gain in peak VO(2) from resynchronisation was peak stress t-IVT (r = 0.71, p<0.001) with every increment of 5 s/min of peak stress t-IVT during native activation predicting an 8% gain in peak VO(2). No conventional measures during native activation at rest or on stress (including QRS duration, Tei index, tissue Doppler intraventricular delay, and resting t-IVT) added significant additional information. CONCLUSIONS: In eligible patients, resynchronisation can acutely augment peak VO(2), possibly through a mechanism of t-IVT shortening. Under native activation, long t-IVT during peak stress is the single best predictor of acute resynchronisation-mediated increment in peak VO(2).

A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction.

BACKGROUND: Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown. AIM: The aim of this study was to determine the prevalence and characteristics of SDB in male patients with NYHA class II symptoms of CHF. METHODS AND RESULTS: 55 male patients with mild symptomatic CHF underwent assessment of quality of life, echocardiography, cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive sleep apnoea. SDB patients had steeper VE/VCO(2) slope [median (inter-quartile range) 31.1 (28-37) vs. 28.1 (27-30) respectively; p=0.04], enhanced chemoreflexes to carbon dioxide during wakefulness [mean+/-sd: 2.4+/-1.6 vs. 1.5+/-0.7 %VE Max/mmHg CO(2) respectively; p=0.03], and significantly higher levels of brain natriuretic peptide and endothelin-1 compared to patients without SDB. No differences in left ventricular ejection fraction, percent predicted peak oxygen uptake, or symptoms of SDB were observed. CONCLUSIONS: A high prevalence of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be differentiated by symptoms or by routine cardiac assessment making clinical diagnosis of SDB in CHF difficult.

Can heart rate variation rule out sleep-disordered breathing in heart failure?

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne-Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF. In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles. Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea-hypopnoea index>20 events.h-1 and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea-hypopnoea cut-off of 30 events.h-1. In conclusion, these results suggest that spectral analysis of heart rate may be useful as a "rule-out test" for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.