Abstract Aims The overall aim was to identify sub‐clinical cardiac abnormalities by echocardiography in patients with chronic kidney disease (CKD) stages 3 and 4 and to investigate underlying mechanisms. Methods and results Ninety‐one patients with CKD stages 3 and 4, without a diagnosis of heart disease, and 41 healthy matched controls were included in this cross‐sectional study. Cardiac morphology and function were analysed with Doppler echocardiography and coronary flow velocity reserve (CFVR) in response to adenosine was measured in the left anterior descendent artery to detect coronary microvascular dysfunction (CMD). All study subjects had a left ventricular (LV) ejection fraction > 50%. Patients with CKD showed statistically significant increases in left atrial volume index and transmitral and pulmonary vein flow velocities during atrial contraction and prolonged LV isovolumetric relaxation time. Patients with CKD had significantly reduced CFVR vs. controls (2.74 ± 0.86 vs. 3.40 ± 0.89, P < 0.001), and 43% of patients were classified as having CMD compared with 9% of controls (P = 0.001). Conclusions Patients with CKD stages 3 and 4, without a diagnosis of heart disease, showed early abnormalities in LV diastolic function that did not fulfil the criteria for LV dysfunction according to current guidelines. A large proportion of CKD patients had CMD, suggesting that microvascular abnormalities may have a pathogenic role in the development of heart failure in this patient group.

Background/Aims: Cardiovascular disease is the major cause of death in patients with chronic kidney disease (CKD). Rats with adenine-induced chronic renal failure (ACRF) develop severe renal insufficiency and metabolic abnormalities that closely resemble those in patients with uremia. The aim of the present study was to determine left ventricular (LV) morphology and function in rats with ACRF. Methods: Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls, C). After 9-13 weeks animals were anesthetized with isoflurane and cardiac function was assessed both by echocardiography and by LV catheterization. Results: Rats with ACRF showed increases in serum creatinine (323±107 vs. 33±5 µM, P< 0.05), mean arterial pressure (115±6 vs. 106±7 mmHg, P< 0.05) and LV weight (3.4±0.3 vs. 2.5±0.2 mg/kg, P< 0.05) vs. controls. Rats with ACRF had reduced early diastolic tissue Doppler velocities in the LV, enlarged left atrial diameter (4.8±0.8 vs. 3.5±0.4 mm, P< 0.05) and elevated LV end-diastolic pressure (15±5 vs. 8±1 mmHg, P< 0.01). Cardiac output was increased in ACRF rats (211±66 vs. 149±24 ml/min, P< 0.05) and systolic function preserved. In the LV of ACRF rats there were statistically significant (P< 0.05) increases in cardiomyocyte diameter, proliferation and apoptosis, while there was no difference between groups in fibrosis. Conclusion: Rats with ACRF develop LV hypertrophy and diastolic dysfunction while systolic performance was preserved. There was an increased hypertrophy and apoptosis of cardiomyocytes in the LV of ACRF rats. The cardiac abnormalities in ACRF rats resemble those in patients with CKD in which heart failure with preserved ejection fraction is common. Hence, this experimental model is well suited for studying pathophysiological mechanisms in chronic renocardiac syndromes.

Background: Obstructive sleep apnea (OSA) has been associated with worse diastolic function in patients with coronary artery disease (CAD). This analysis determined whether continuous positive airway pressure (CPAP) treatment would improve diastolic function in CAD patients with nonsleepy OSA.Methods: Between December 2005 and November 2010, 244 revascularized CAD patients with nonsleepy OSA (apnea-hypopnea index (AHI) >= 15/h, Epworth Sleepiness Scale [ESS] score < 10) were randomly assigned to CPAP or no-CPAP. Echocardiographic measurements were obtained at baseline, and after 3 and 12 months.Results: A total of 171 patients with preserved left ventricular ejection fraction (>= 50%), no atrial fibrillation or severe valve abnormalities, and technically adequate echocardiogramsat baseline and follow-up visits were included (CPAP, n = 87; no-CPAP, n = 84). In the intention-to-treat analysis, CPAP had no significant effect on echocardiographic parameters of mild (enlarged left atrium or decreased diastolic relaxation velocity) or worse (increased E/e filling index [presumed elevated left ventricular filling pressure]) diastolic function. Post-hoc analysis revealed a significant association between CPAP usage for = 4 h/night and an increase in diastolic relaxation velocity at 12 months' follow-up (odds ratio 2.3, 95% confidence interval 1.0-4.9; p = 0.039) after adjustment for age, sex, body mass index, and left atrium diameter at baseline.Conclusions: CPAP did not improve diastolic dysfunction in CAD patients with nonsleepy OSA. However, good CPAP adherence was significantly associated with an increase in diastolic relaxation velocity after one year. (C) 2017 Elsevier B.V. All rights reserved.

BackgroundWhile left atrial (LA) enlargement is known as an early sign of left heart disease with prognostic implications in heart failure (HF), the importance of right atrial (RA) enlargement is less well studied, and the prognostic implications of interatrial size comparison are insufficiently understood. The aim of this study was to test the hypothesis that RA area larger than LA area in apical four‐chamber view is associated with all‐cause mortality in elderly patients with HF independent of left ventricular ejection fraction (LVEF).MethodsRetrospectively, 289 patients above 65 years hospitalized for HF between April 2007 and April 2008, and who underwent an echocardiogram, were enrolled. All‐cause mortality was registered during a follow‐up of at least 56 months. Baseline parameters measured were RA area, LA area, LA volume, LVEF, left ventricular mass (LVM), tissue Doppler systolic velocity of right ventricular free wall (SmRV), presence of severe tricuspid regurgitation (TR), tricuspid gradient, central venous pressure, systolic pulmonary artery pressure, as well as some parameters of diastolic function.ResultsIn univariate analysis RA larger than LA was associated with all‐cause mortality (hazard ratio [HR] of 1.88, P<.001). The relation of RA larger than LA to all‐cause mortality remained even after adjusting for age, heart rate, LVEF, atrial fibrillation, percutaneous coronary intervention, LVM index, LA volume index, SmRV, and the presence of severe TR (HR: 1.79, P=.04).ConclusionRA larger than LA, independently of LVEF, is associated with all‐cause mortality in elderly patients hospitalized due to HF.

Background: We recently demonstrated that obstructive sleep apnea (OSA) was associated with worse diastolic function in patients with coronary artery disease (CAD). In the current randomized controlled study, we addressed if continuous positive airway pressure (CPAP) treatment would improve diastolic function in CAD patients with nonsleepy OSA. Methods: Between December 2005 and November 2010, 244 revascularized CAD patients with nonsleepy OSA (apnea-hypopnea index (AHI)≥15 h-1, and Epworth Sleepiness Scale [ESS] score <10) were randomly assigned to CPAP or no-CPAP. Echocardiographic measurements were obtained at baseline, after 3 and 12 months, respectively. Results: In all, 171 patients (87 assigned to CPAP; 84 to no-CPAP) with preserved left ventricular ejection fraction ≥50%, and with no atrial fibrillation or severe valve abnormalities, and with technically adequate echocardiograms at baseline and at the follow-ups, were included. CPAP had no significant impact on echocardiographic parameters of the diastolic dysfunction (enlarged left atrium, decreased mean é tissue velocity, or increased E/é filling index) in the intention-to-treat population. On-treatment analysis revealed a significant increase in diastolic relaxation velocity in patients using CPAP for ≥4 h/night (odds ratio 2.3, 95% confidence interval 1.0-4.9; p=0.039) after adjustment for age, sex, body-mass-index, and left atrium diameter at baseline. Conclusion: CPAP prescription did not improve diastolic dysfunction in CAD patients with nonsleepy OSA. However, a significant increase in diastolic relaxation velocity was observed after one year in those compliant with the treatment.

Background: The motion of the interatrial septum primum (septum) is dependent on the interatrial pressure relation, normally with slightly higher pressure in the left atrium and the septum bulging toward the right atrium. The aim of this study was to explore the physiologic mechanisms that reverse interatrial pressures and provoke leftward bulging of septum (LBA). The hypothesis was that both left ventricular unloading with nitroglycerin and sustained Valsalva strain would independently provoke LBA and that their combination would further intensify the effect.Methods: Prospectively collected transesophageal echocardiography recordings from 13 patients with obstructive sleep apnea were retrospectively analyzed for the presence or absence of LBA during resting respiration and during Valsalva strain. In each condition, LBA beats were counted at time points before and after nitroglycerin spray had been administered, which enabled a comparison of the independent effects and the combined effect of the nitroglycerin and the Valsalva maneuver. An LBA beat was defined as a heartbeat displaying any LBA during the cardiac cycle.Results: Nitroglycerin increased the proportion of LBA beats significantly during resting respiration, from 21 +/- 27% to 54 +/- 43% (P = .008). During Valsalva strain, the proportion increased with nitroglycerin spray from 48 +/- 21% to 80 +/- 17% (P = .001). After nitroglycerin administration, LBA occurred in at least three beats during strain in all Valsalva periods.Conclusions: Unloading of the left ventricle by nitroglycerin administration and by sustained Valsalva strain independently provoked LBA. The combination of these two interventions further intensified the effect.

Background: Diastolic dysfunction is common in patients with coronary artery disease (CAD). We hypothesize that patients with CAD and preserved left ventricular ejection fraction (LVEF) and obstructive sleep apnea (OSA) will have worse diastolic function than similar patients without OSA.Material and methods: We analyzed sleep-study recordings and echocardiographic measurements obtained at baseline in a randomized controlled trial (RICCADSA) of revascularized patients with CAD who had LVEF of at least 50%. OSA was defined as an apnea-hypopnea-index (AHI) >= 15 events/h, and, no OSA, as an AHI <5. Worse diastolic function was defined as assumed elevated left ventricular filling pressure based on peak flow velocity in early diastole/Tissue Doppler of early diastolic ventricular filling (E/e) of >13 (or >9 in patients with an enlarged left atrial diameter [>= 39 mm for women and >= 40 mm for men]).Results: Data from 431 patients were evaluated (mean age: 63.7 +/- 8.8 y; men: 82.5%; OSA: n = 331). Worse diastolic function was more common among the patients with OSA than those without (54.4% vs 41.0%, p = 0.019). In multivariate analysis, OSA was associated with worse diastolic function (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.13; 3.18) adjusted for female sex (OR 2.28, 95% CI 1.28; 4.07), hypertension (OR 1.84, 95% CI 1.20; 2.82), and diabetes mellitus (OR 2.45, 95% CI 1.42; 4.23). Age >= 60 years, obesity, and current smoking were nonsignificant.Conclusions: In this cohort with CAD and preserved LVEF, OSA was associated with worse diastolic function independent of the traditionally recognized risk indicators. (C) 2014 Elsevier B.V. All rights reserved.

Background: Contrast injections during transesophageal echocardiography for patent foramen ovale (PFO) detection may be false negative. The characteristics of false-negative injections were studied retrospectively.Methods: Contrast transesophageal echocardiography was analyzed for the presence or absence of two characteristics: leftward bulging of the interatrial septum and dense contrast filling of the region of the right atrium adjacent to the interatrial septum.Results: Two hundred forty-seven injections were administered to 14 patients with PFOs, and 130 (53%) were false negative. The absence of either characteristic during a single injection resulted in low sensitivity for PFO detection of 7%. When the two characteristics were present at the same time, the sensitivity for PFO detection after a single injection was as high as 95%.Conclusions: The simultaneous presence of both leftward bulging of the interatrial septum and dense contrast filling of the region in the right atrium, adjacent to the interatrial septum, is a prerequisite for PFO detection, and if either characteristic is missing, the injection is inconclusive. (J Am Soc Echocardiogr 2010; 23: 1136-42.)

The pulsed Doppler early diastolic left ventricular (LV) tissue (e)-blood (E) onset temporal relationship (e-E) is suggested to predict pulmonary capillary wedge pressure (PCWP), through the formulas: tau = 32 + 0.7(e-E) and PCWP = LV end-systolic pressure x e(-IVRT/tau). Small changes/errors in E could influence the quotient IVRT/tau by oppositely affecting IVRT and e-E. At rest in 50 healthy individuals we noted: e-E: 2 +/- 14 ms; IVRT: 89 +/- 17 ms; calculated tau: 33 +/- 110 ms; and PCWP: 9 +/- 9 mmHg (>12 mmHg in 28%). Non-pharmacological preload alterations in 14 individuals rendered an intraindividual 'PCWP'-fluctuation of up to 40 mmHg. This application may therefore not be clinically robust. (C) 2006 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.

Although pulsed Doppler echocardiography estimates current left ventricular (LV) filling, left atrial (LA) size reflects LV filling and pressure over time. However, the wide normal LA size range may blunt this diagnostic tool. Our objective was to compare the intraindividual atrial area difference (LA--right atrial [RA] area) and absolute LA area in their detection of a LA enlargement with respect to the degree of current LV filling impairment. We examined patients with acute coronary syndromes in sinus rhythm and without valvular disease (n = 154), and age- and gender-matched healthy controls (n=50) with echocardiography, applying pulsed Doppler international recommendations to group the patients according to the LV filling pattern: 0, normal; 1, delayed relaxation; 2, an isolated abnormal mitral pulmonary venous A-wave duration difference; 3, pseudonormal; and 4, restrictive. The LA and RA areas were measured in the 4-chamber view. Control values defined the normal range of: absolute LA area, LA area adjusted for body height, and LA-RA area. These areas indicated a LA enlargement in: (1) controls, 2%, 2%, and 4%, respectively; (2) patients with LV filling graded as normal/mildly impaired (groups 0 and 1), 15%, 17%, and 46%, respectively; moderately impaired (group 2), 26%, 29%, and 52%, respectively; and severely impaired (group 3 and 4), 42%, 38%, and 54%, respectively. Unequally sized atria appear to detect LA enlargement sensitively, especially when Doppler evidence of LV filling pathology is sparse. Clinically, with no obvious current cause for LA enlargement, a diagnosed "atrial size inequality" may still indicate a history of such causes.

AIM:A ratio>15 between the early diastolic pulsed Doppler velocities of the mitral inflow (E) and the basal left ventricular (LV) tissue (e) has been demonstrated to predict an elevated LV filling pressure (FP). An elevated LVFP implies an elevated right ventricular pressure (RVp). In order to investigate the sensitivity of the E/e filling index, we compared E/e and RVp, in their ability to identify a Doppler-assumed elevation of LVFP.METHODS AND RESULTS:Application of pulsed Doppler international recommendations grouped 134 patients with acute coronary syndromes (ACS) and 50 age- and sex-matched controls, according to LV filling: normal; delayed relaxation; an isolated pathological mitral-pulmonary venous-A-wave-duration difference; pseudo normal; or a restrictive filling pattern. An E/e>15 and an RVp>30 mmHg showed the following (%) sensitivity (32/94), specificity (95/76), positive (68/59), and negative (80/97) predictive values of a Doppler-assumed elevation of LVFP, in terms of either a pseudo normal or a restrictive filling pattern.CONCLUSION:The low sensitivity of E/e to detect a Doppler-assumed elevation of LVFP could limit its clinical usefulness as a single variable, in ACS. The high sensitivity and negative predictive value of RVp support its use as an additional LV filling variable in these patients.

Pulsed tissue Doppler can measure myocardial velocities with high temporal resolution. Our aim was to determine the onset timing of the regional left ventricular longitudinal early lengthening (e) in relation to the mitral inflow (E) in acute coronary syndromes. We applied pulsed tissue Doppler to the septal, lateral, inferior, and anterior left ventricular basal walls of 160 patients with acute coronary syndromes and 60 control subjects. Maximum systolic and early diastolic velocities were lower for patient than for control walls (6.1 +/- 1.7 vs 7.9 +/- 1.4 cm/s, P < .0001, and 6.9 +/- 2.3 vs 10.0 +/- 2.3 cm/s, P < .0001, respectively) and e started later than E (12 +/- 30 vs 2 +/- 19 milliseconds later, P < .0001). All 3 variables related to the degree of visual left ventricular wall pathology. The intraindividual time range for all 4 e starts was wider for patients (43 +/- 27 vs 30 +/- 18 milliseconds, P < .0001). Our results show that pulsed tissue Doppler can identify a delayed and asynchronous initial wall lengthening in acute coronary syndromes.

Approximately one third of free wall infarct ruptures are subacute and theoretically accessible for surgery. Two-dimensional echocardiography is an important tool in the early diagnosis of cardiac rupture. We report the successful treatment of a 74-year-old woman with subacute free wall rupture, who is still alive 3 years after surgery.