Is serial determination of inspiratory muscle strength a useful prognostic marker in chronic heart failure?

BACKGROUND: Little data exists on the prognostic role of inspiratory muscle strength (PImax) in chronic heart failure (CHF). Training studies, however, frequently use it as a therapeutic target and surrogate marker for prognosis. The prognostic value of changes of PImax that allow this extrapolation is unknown. DESIGN: Patients with stable CHF were prospectively included and 1-year and all-time event rates recorded for endpoint analysis. METHODS: In 158 patients (85% men; New York Heart Association functional class: 2.4+/-0.6), PImax was measured along with clinical evaluations at two visits, the initial visit and the second visit, 6.4+/-1.4 months apart. The mean follow-up was 59+/-34 months. RESULTS: Overall, 59 patients (37%) reached the primary endpoint of death or hospitalization (endpoint positive), and overall mortality rate (secondary endpoint) was 26% (42 patients). PImax did not differ between endpoint-negative and endpoint-positive patients, both at the initial and at the second visit (8.3+/-5.6 vs. 7.3+/-3.4 kPa and 8.8+/-6.0 vs. 7.9+/-3.6 kPa, respectively; P=NS), and both groups showed increased PImax (0.6+/-2.6 vs. 0.6+/-2.8 kPa; P=NS). Cox analyses found neither the absolute nor the relative change of PImax to be significant predictors for the primary and secondary endpoints (P=NS for both), both for the 1-year and for the all-time event rates. Endpoint rates did not differ between patients showing increasing or decreasing PImax (P=NS; relative risk (RR): 0.77; 95% confidence interval: 0.47-1.27). CONCLUSION: Trials focusing on inspiratory muscle function should use the actual levels of PImax as a surrogate marker to represent prognostic information, rather than relative or absolute changes. This is the first study to investigate the prognostic information of the changes of PImax over time, regarding both short-term and long-term morbidity and mortality in patients with stable CHF.     

Anatomically oriented right ventricular volume measurements with dynamic three-dimensional echocardiography validated by 3-Tesla magnetic resonance imaging.

OBJECTIVES: We tested a newly developed 4-dimensional (4D) right ventricular (RV) analysis method for computing RV volumes for both 3-dimensional (3D) ultrasound (US) and magnetic resonance (MR) images. BACKGROUND: Asymmetry and the anatomical complexity of the RV make accurate determination of RV shape and volume difficult. METHODS: Thirty patients, 14 with grossly normal cardiac anatomy and 16 with major congenital heart disease, were studied at the same visit with both 3D echocardiography (echo) and magnetic resonance imaging (MRI) for RV size and function. Ultrasound images were acquired on a Philips 7500 system (Philips Medical Systems, Andover, Massachusetts) with a matrix-array transducer (real-time 3D echo) with full volume sweeps from apical and subcostal views. Sagittal, 4-chamber, and coronal views were derived for contour detection (all 12 to 24 slices). The MR images were acquired with a 3-T MRI magnet with segmented cine-loop gradient echo sequences in short- and rotated long-axis views to cover the RV inflow, body, and outflow tract. The RV volumes were analyzed with the new software applicable to 3D echo MR images. RESULTS: New software aided delineation of the RV free wall, tricuspid valve, RV outflow tract, and apex on 3D echo volumes. Although there was a slightly higher variability measuring right ventricular ejection fraction (RVEF) and volumes obtained by US compared with MRI, both imaging methods showed closely correlated results. The RVEF was measured with 4% variability for US and 5% variability for MRI with a correlation coefficient of r = 0.91. The RV end-diastolic volume was measured at 70.97 +/- 15.0 ml with 3D US and at 70.06 +/- 14.8 ml with MRI (r = 0.99), end-systolic volume measured 39.8 +/- 10.4 ml with 3D US and 39.1 +/- 10.2 ml with MRI (r = 0.98). CONCLUSIONS: The new RV analysis software allowed validation of the accuracy of 4D echo RV volume data compared with MRI.     

Increased SR Ca2+ cycling contributes to improved contractile performance in SERCA2a-overexpressing transgenic rats

OBJECTIVE: Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transgenic rat hearts (TG) results in improved contractility. However, it was not clear whether TG have improved contractility due to frequency-dependent improved SR Ca2+ handling. METHODS: Therefore, we characterized TG (n=35) vs. wild-type (WT) control rats (n=39) under physiological conditions (37 degrees C, stimulation rate <8 Hz). Twitch force, intracellular Ca2+ transients ([Ca2+]i), and SR Ca2+ content were measured in isolated muscles. The contribution of transsarcolemmal Ca2+ influx (I(Ca)) through L-type Ca2+ channels (LTCC) and reverse mode NCX (I(Na/Ca)) to Ca2+ cycling were studied in isolated myocytes. RESULTS: With increasing frequency, force increased in TG muscles by 168+/-35% (8 Hz; P<0.05) and SR Ca2+ content increased by maximally 118+/-31% (4 Hz; P<0.05). In WT, there was a flat force-frequency response without changes in SR Ca2+ content. Relaxation parameters of force and [Ca2+]i decay were accelerated at each frequency in TG vs. WT by approximately 10%. At prolonged rest intervals (<240 s), force and SR Ca2+ content increased significantly more in TG. Consequently, absolute SR Ca2+ content measured in myocytes was increased approximately 2-fold in TG. Transsarcolemmal Ca2+ fluxes estimated by I(Ca) (at 0 mV -10.2+/-1.1 vs. -16.9+/-1.3 pA/pF) and I(Na/Ca) (0.17+/-0.02 vs. 0.46+/-0.05 pA/pF) were decreased in TG vs. WT (P<0.05), whereas NCX and LTCC protein expression was only slightly reduced (P=n.s.). CONCLUSION: In summary, SERCA2a-overexpression improved contractility in a frequency-dependent way due to increased SR Ca2+ loading whereas transsarcolemmal Ca2+ fluxes were decreased.     

Mitral valve prolapse

Mitral valve prolapse is a common valvular abnormality that is the most common cause of severe non-ischaemic mitral regurgitation in the USA. The overall prognosis of patients with mitral valve prolapse is excellent, but a small subset will develop serious complications, including infective endocarditis, sudden cardiac death, and severe mitral regurgitation. We present a comprehensive review of mitral valve prolapse, examining normal mitral anatomy, the clinical and echocardiographic features of mitral valve prolapse, and the pathophysiology and genetics of the disorder. We discuss the contemporary management of both asymptomatic and symptomatic prolapse, with particular attention to the timing and technique of surgical repair. We conclude that echocardiography is the method of choice for diagnosing mitral valve prolapse, that clinical and echocardiographic features can predict which patients with prolapse are at highest risk for complications, and that mitral valve repair is the treatment of choice for symptomatic prolapse.     

Abnormalities of pulmonary artery wedge pressures in sleep-induced apnea

Six patients with sleep apnea syndrome were studied with continuous hemodynamic monitoring during sleep. Sleep apnea had been previously documented with an average number of apneas per hour of sleep ranging from 23 to 93 (mean 63). There was a significant decrease in heart rate during sleep (82 ± 5 to 69 ± 6, P < 0.01). There was a significant rise in systemic blood pressure (103 ± 2 mm Hg to 116 ± 6 mm Hg, P < 0.05) and pulmonary artery pressure (20 ± 1 mm Hg to 32 ± 5 mm Hg) during sleep. In addition, pulmonary artery wedge pressure increased (12 ± 2 mm Hg to 20 ± 3 mm Hg, P < 0.05) during sleep and 5 of the 6 patients developed an abnormal pulmonary wedge pressure. There was a significant decrease in P_O2 during sleep (71 ± 3 mm Hg to 49 ± 2 mm Hg, P < 0.005). These findings suggest that increases in pulmonary wedge pressures may be contributing to increase in pulmonary artery pressures in these patients during sleep.     

Intravascular ultrasonic comparative analysis of degree of intimal hyperplasia produced by four different stents in the coronary arteries

Intravascular ultrasound studies were performed at angiographic follow-up on 121 native coronary lesions treated with 1 bare metal stent (n = 50), high-dose dexamethasone-eluting stents (n = 18), non-polymer-based paclitaxel-eluting stents (n = 18), or sirolimus-eluting stents (n = 35). Paclitaxel- and sirolimus-eluting stents reduced mean intimal hyperplasia thickness compared with bare metal stents by 49% and 90% (p = 0.048 and p <0.001), respectively, whereas mean intimal hyperplasia thickness treated with dexamethasone-eluting stents was similar to those lesions treated with bare metal stents.     

Alterations of the CARD15/NOD2 gene and the impact on management and treatment of Crohn's disease patients

The recent identification of the CARD15/NOD2 gene as a susceptibility locus for Crohn's disease represents an important step towards the delineation of the immunopathogenesis of inflammatory bowel disease. CARD15 functions as an intracellular receptor for bacterial components and thus represents an important link between inflammatory bowel disease and innate immunity. Three major CARD15/NOD2 gene mutations have been associated with Crohn's disease in Caucasians in several independent studies. Together, they explain about 20% of the genetic susceptibility for Crohn's disease. Genotype-phenotype analyses demonstrated an association of these mutations with ileum-specific disease, an increased incidence of the fibrostenotic phenotype and an earlier age of disease onset. Beside these associations, no other relationship between the CARD15/NOD2 genotype and disease behavior or response to treatment has been detailed so far. Thus, the clinical impact of knowing the patient's genotype is limited at this time. Screening for CARD15 mutations in order to identify high-risk individuals or to introduce an individualized disease management is therefore currently not recommended.     

Microscopic polyangiitis and polyarteritis nodosa: how and when do they start?

OBJECTIVE: To describe initial clinical symptoms attributable to microscopic polyangiitis (MPA) or polyarteritis nodosa (PAN). METHODS: We retrospectively reviewed the medical files of 72 patients (mean followup 6.7 years) with biopsy-proven MPA (n = 36) or PAN (n = 36). RESULTS: Initial manifestations were similar in both entities except for peripheral neuropathy (P = 0.02) and gastrointestinal tract involvement (P = 0.006), which were significantly more frequent in PAN, and general signs alone in MPA (8%; P = 0.02). The mean time to diagnosis was 9.8 +/- 19.4 months; 35% of the patients died and 26% relapsed; significantly more MPA than PAN patients relapsed (P = 0.03). Time to diagnosis >/=90 days was associated with a trend toward more patients relapsing (P = 0.12), but not with an increased risk of mortality. CONCLUSION: Initial symptoms of MPA and PAN are usually nonspecific and last for several months before the diagnosis is made. A longer time to diagnosis is associated with a tendency to a higher relapse rate.