Background: Patients with hypertrophic cardiomyopathy (HCM) show various physical findings, but their clinical significance has not been systematically evaluated.Methods and Results: This study ...evaluated 105 consecutive patients with HCM who had undergone phonocardiography and external pulse recording. Physical examinations included a visible jugular a-wave (Jug-a), audible 4th sound (S4), and double or sustained apex beat. The primary outcome was a composite of all-cause death and hospitalization for cardiovascular disease. A total of 104 non-HCM subjects served as controls. The prevalence of visible Jug-a in the seated or supine position, audible S4, and a sustained or double apex beat in patients with HCM were 10%, 71%, 70%, 42%, and 27%, respectively, all of which were significantly higher than in the controls (0%, 20%, 11%, 17%, and 2%; P<0.001 for all comparisons). The combination of visible Jug-a in the supine position and audible S4 yielded a specificity of 94% and sensitivity of 57%. During a follow-up period of 6.6 years, 6 patients died and 10 were hospitalized. The absence of audible S4 was a predictor of cardiovascular events (hazard ratio, 3.91; 95% confidence interval, 1.41 to 10.8; P=0.005).Conclusions: Detection of these findings has clinical importance in the diagnosis and risk stratification of HCM prior to the use of advanced imaging techniques.
Background:The 4th heart sound (S4) is commonly heard in patients with hypertrophic cardiomyopathy (HCM). The 3rd heart sound (S3) is also audible in HCM patients regardless of the presence or ...absence of heart failure. These extra heart sounds may be associated with myocardial fibrosis because myocardial fibrosis has been suggested to affect left ventricular compliance.Methods and Results:The present retrospective study evaluated 53 consecutive HCM patients with sinus rhythm who had no symptoms of heart failure and underwent an initial assessment including phonocardiography, echocardiography, and late gadolinium enhancement (LGE) magnetic resonance imaging (MRI). S3 was detected on phonocardiography in 13% of all patients, and S4 was recorded in 75% of patients. Patients with S3 had a higher incidence of LGE and larger LGE volumes (86% and 11.5±2.4 g/cm, respectively) than patients without S3 (33% and 2.5±0.8 g/cm, respectively; P=0.02 and P=0.002). The presence of S4 was not associated with MRI findings, including the incidence of LGE and LGE volume. The diagnostic value of S3 for the detection of LGE was highly specific (97%), with a low sensitivity (29%).Conclusions:Myocardial fibrosis, as assessed by LGE, was associated with S3 but not with S4 in patients with HCM. These results may contribute to the risk stratification of patients with HCM.
Heart failure (HF) is often accompanied by skeletal muscle weakness and exercise intolerance, which are known as prognostic factors of HF. Comprehensive evaluation of physical function is important, ...but it is not commonly conducted because of the lack of equipment or appropriate expertise. Measurement of rectus femoris diameter (RFD) by ultrasound is convenient and noninvasive, but it has not been clarified that RFD could represent physical functions in HF patients. This study evaluated 185 consecutive HF patients and underwent assessment including RFD, grip power (GP), knee extension strength (KES), skeletal muscle index (SMI), nutrition status, cardiopulmonary exercise testing, and New York Heart Association (NYHA) functional class. RFD was related with NYHA class and significantly correlated with GP, KES, SMI, body mass index, pre-albumin level, geriatric nutritional risk index, and peak
V
O
2
(
r
= 0.631, 0.676, 0.510, 0.568, 0.380, 0.539, 0.527, respectively;
p
< 0.001). Multivariate regression analysis revealed that estimated glomerular filtration rate (
β
= 0.551) and RFD (
β
= 0.326) were predictive factors of peak
V
O
2
. Gender, age, brain natriuretic peptide level, left ventricular ejection fraction, and hemoglobin level were the other explanatory parameters. The cut off value of RFD for sarcopenia diagnosis was estimated as 15 mm (sensitivity = 0.767 and specificity = 0.808). RFD is a simple and useful marker which reflects skeletal muscle strength/volume, exercise tolerance, nutrition status, and NYHA class. It is also associated with sarcopenia in HF patients.
Simultaneous left atrial (LA) and left ventricular (LV) 3-dimensional (3D) echocardiographic volume measurements enable the quantifying of precise LA function, by virtue of their independence on any ...geometric assumption and capability of measurement for net LA conduit volume. We sought to elucidate the impact of conventional Doppler LV diastolic property on LA volume and function derived from this method. Our study subjects consisted of 381 patients who underwent 3D echocardiography. From LA time-volume curve, maximum and minimum volume index (VI) and VI before atrial contraction (LAVIpre-c) were determined; subsequently, active emptying volume was calculated as LAVIpre-c − minimum LAVI. From LA and LV volume measurement, conduit volume was calculated as LV stroke VI − (maximum LAVI − minimum LAVI). LA volume increased depending on the severity of diastolic dysfunction. Compared with patients with normal diastolic function, LA booster pump function, as the contribution of active emptying volume to LV filling, was higher in those with mild diastolic dysfunction. Additionally, it gradually decreased as diastolic dysfunction was advanced from mild to moderate and moderate to severe degree (23.2 ± 15.5%, 29.5 ± 15.1%, 25.1 ± 16.2%, 14.9 ± 14.1%, respectively; p <0.001). Contrarily, conduit contribution was significantly higher in patients with severe diastolic dysfunction than in those with mild diastolic dysfunction; furthermore, conduit function tended to increase, reciprocally to booster pump function, as diastolic dysfunction grade was advanced (39.1 ± 28.8%, 36.8 ± 26.2%, 42.7 ± 25.6%, 52.9 ± 26.2%, respectively; p = 0.034). In conclusion, simultaneous LA and LV volumetric analyses through 3D echocardiography clearly demonstrate the characteristic LA functional alterations following LA dilation caused by LV diastolic dysfunction.
Late rather than acute kidney injury after percutaneous coronary intervention (PCI) has been recently recognized as a predictor of future adverse events in patient with coronary artery disease. The ...risk-predicting models for acute kidney injury reported by Mehran et al., Bartholomew et al., and Tsai et al. were derived from a large cohort and externally validated, although the applicability of these models for predicting late kidney injury is unknown. A total of 327 patients undergoing elective PCI procedures were included. We calculated the three scores and tested their diagnostic ability for predicting late kidney injury (> 6 months after PCI), defined as an increase in creatinine levels ≥ 0.3 mg/dl or ≥ 50% from baseline. During the median follow-up period of 28 months, 27 (8.3%) patients had late kidney injury. All three scores significantly predicted late kidney injury, among which the score by Tsai et al. had a better diagnostic ability (area under the curve 0.83, best cut-off value 14,
p
< 0.001). With the best cut-off value, patients with Tsai score ≥ 14 had a significantly higher rate of late kidney injury than their counterpart (27.4% vs. 2.8%,
p
< 0.001). In conclusion, established risk scores for acute kidney injury may be useful for predicting late kidney injury after PCI in patients with chronic coronary syndrome.
Background:Cardiac conduction disturbance (CD) is the most frequent complication following transcatheter aortic valve replacement (TAVR). This study examined whether the anatomy of the membranous ...septum (MS) could provide useful information about the risk of CD following TAVR with a balloon-expandable valve (BEV).Methods and Results:Among 132 consecutive patients, 106 (mean age, 85.6±5.1 years; 75 females) were included in the study. Using preoperative CT and angiography, MS length and implantation depth (ID) were assessed. The MS length minus the prosthesis ID was calculated (∆MSID). Correlation between CD, defined as new-onset left-bundle branch block (LBBB) or the need for permanent pacemaker (PPM) within 1 week after the procedure, and MS length were evaluated. A total of 19 patients (18%) developed CD following TAVR. MS length was significantly shorter in these patients than in those without CD (5.3±1.3 vs. 6.6±1.4; P<0.001), and was the important predictor of CD (odds ratio OR: 0.43, 95% confidence interval CI: 0.27–0.69, P<0.001). When considering the pre- and postprocedural parameters, the ∆MSID was smaller in patients with CD (−1.7±1.5 vs. 0.8±1.9, P<0.001), and emerged as the important predictor of CD (OR: 0.47, 95% CI: 0.33–0.69, P<0.001).Conclusions:Short MS is associated with an increased risk of CD after TAVR with BEV.
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction caused by autoantibodies binding to P/Q-type voltage-gated calcium channels. Breakdown of the ...blood-brain barrier and diffusion of cerebellar granule/Purkinje cell-reactive autoantibodies into the CNS are critical for the pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton myasthenic syndrome. We recently found evidence that glucose-regulated protein 78 (GRP78) autoantibodies in the plasma of patients with neuromyelitis optica promote the CNS access of AQP4 autoantibodies. In the present study, we investigated whether the GRP78 autoantibodies in PCD-LEMS IgG boost the brain uptake of cerebellar cell-reactive antibodies across the blood-brain barrier and facilitate cerebellar dysfunction. We first evaluated the effects of purified IgG from PCD-LEMS or PCD patients on the blood-brain barrier function in human brain microvascular endothelial cells using a high content imaging system with nuclear factor κB p65 and intracellular adhesion molecule 1 (ICAM1) immunostaining. Next, we identified GRP78 autoantibodies causing blood-brain barrier permeability in PCD-LEMS IgG by co-immunoprecipitation and the living cell-based antibody binding assays. Exposure of brain microvascular endothelial cells to IgG from PCD-LEMS patients induced nuclear factor κB p65 nuclear translocation, ICAM1 upregulation, reduced claudin-5 expression, increased permeability and increased autocrine IL-1β and IL-8 secretion; the IgG from patients with Lambert-Eaton myasthenic syndrome did not have these effects. We detected GRP78 autoantibodies in the IgG of LEMS-PCD (83.3%, n = 18), but observed fewer in patients with LEMS (6.6%, n = 15) and none were observed in the control subjects (n = 8). The depletion of GRP78 autoantibodies reduced the biological effect of LEMS-PCD IgG on brain microvascular endothelial cells. These findings suggest that GRP78 autoantibodies play a role beyond neuromyelitis optica and that they have direct implications in the phenotypic differences between PCD-LEMS and LEMS.
Background
Patients with hypertrophic cardiomyopathy (HCM) in sinus rhythm commonly show the fourth heart sound (S4). The lack of S4 may be a marker of impaired atrial function in HCM patients with ...sinus rhythm.
Methods and Results
This retrospective study consisted of 47 patients with HCM who had undergone phonocardiography and a cardiopulmonary exercise test. The primary outcome was a composite of cardiac death, stroke, hospitalization for worsening heart failure, and newly developed atrial fibrillation (AF). S4 was detected in 38 of 43 patients with sinus rhythm (88%). Peak oxygen consumption was the highest in 38 sinus rhythm patients with S4 (23.6 ± 5.6 mL/kg/min), middle in five sinus rhythm patients without S4 (19.3 ± 6.7 mL/kg/min), and lowest in four patients with AF (15.7 ± 3.3 mL/kg/min, p = 0.01). After a median of 40.5 months, the incidence of the primary outcome was higher in patients without S4 than in those with S4 (33% vs. 8%; hazard ratio, 6.17; 95% confidence interval, 1.02 – 37.4; p = .04) and higher in sinus rhythm patients without S4 than in those with S4 (60% vs. 8%; hazard ratio, 12.05; 95% confidence interval, 2.31 – 71.41; p = .007).
Conclusions
The absence of S4 on phonocardiography was associated with impaired exercise tolerance and adverse cardiac events in HCM patients with sinus rhythm.
Glomerulopathy with fibronectin deposits (GFND) is a rare hereditary kidney disease with autosomal dominant inheritance. A 21-year-old woman who had been diagnosed with GFND 10 years ago was admitted ...for investigation of a rapid decline in her renal function, hemolytic anemia, and cardiac dysfunction. A renal biopsy showed GFND accompanied by extraglomerular vascular lesions. Comprehensive treatments against hypertension and anemia improved the renal function. Although there have been few reports of vascular lesions in GFND, we suspect that endothelial hyperpermeability resulting from hypertension caused the fibronectin deposition and narrowing of the extraglomerular vascular lumens, thereby accelerating hypertension and inducing hemolytic anemia.
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