The force response of activated striated muscle to length perturbations includes the so-called C-process, which has been considered the frequency domain representation of the fast single-exponential force decay after a length step (phases 1 and 2). The underlying molecular mechanisms of this phenomenon, however, are still the subject of various hypotheses. In this study, we derived analytical expressions and created a corresponding computer model to describe the consequences of independent acto-myosin cross-bridges characterized solely by 1), intermittent periods of attachment (t(att)) and detachment (t(det)), whose values are stochastically governed by independent probability density functions; and 2), a finite Hookian stiffness (k(stiff)) effective only during periods of attachment. The computer-simulated force response of 20,000 (N) cross-bridges making up a half-sarcomere (F(hs)(t)) to sinusoidal length perturbations (L(hs)(t)) was predicted by the analytical expression in the frequency domain, (F(hs)(omega)/L(hs)(omega))=(t(att)/t(cycle))Nk(stiff)(iomega/(t(att)(-1)+iomega)), where t(att) = mean value of t(att), t(cycle) = mean value of t(att) + t(det), k(stiff) = mean stiffness, and omega = 2pi x frequency of perturbation. The simulated force response due to a length step (L(hs)) was furthermore predicted by the analytical expression in the time domain, F(hs)(t)=(t(att)/t(cycle))Nk(stiff)L(hs)e(-t/t(att)). The forms of these analytically derived expressions are consistent with expressions historically used to describe these specific characteristics of a force response and suggest that the cycling of acto-myosin cross-bridges and their associated stiffnesses are responsible for the C-process and for phases 1 and 2. The rate constant 2pic, i.e., the frequency parameter of the historically defined C-process, is shown here to be equal to t(att)(-1). Experimental results from activated cardiac muscle examined at different temperatures and containing predominately alpha- or beta-myosin heavy chain isoforms were found to be consistent with the above interpretation.
Metabolic syndrome is associated with incident cardiovascular events. Combined use of MetS and FMD identifies those who are at higher risk of cardiovascular events. Metabolic syndrome and noninvasive FMD testing can be used concurrently for cardiovascular risk prediction.
; for the Shared Decision Making for Atrial Fibrillation (SDM4AFib) Trial Investigators IMPORTANCE Shared decision-making (SDM) about anticoagulant treatment in patients with atrial fibrillation (AF) is widely recommended but its effectiveness is unclear. OBJECTIVE To assess the extent to which the use of an SDM tool affects the quality of SDM and anticoagulant treatment decisions in at-risk patients with AF. DESIGN, SETTING, AND PARTICIPANTS This encounter-randomized trial recruited patients with nonvalvular AF who were considering starting or reviewing anticoagulant treatment and their clinicians at academic, community, and safety-net medical centers between January 30, 2017 and June 27, 2019. Encounters were randomized to either the standard care arm or care that included the use of an SDM tool (intervention arm). Data were analyzed from August 1 to November 30, 2019. INTERVENTIONS Standard care or care using the Anticoagulation Choice Shared Decision Making tool (which presents individualized risk estimates and compares anticoagulant treatment options across issues of importance to patients) during the clinical encounter. MAIN OUTCOMES AND MEASURES Quality of SDM (which included quality of communication, patient knowledge about AF and anticoagulant treatment, accuracy of patient estimates of their own stroke risk [within 30% of their estimate], decisional conflict, and satisfaction), decisions made during the encounter, duration of the encounter, and clinician involvement of patients in the SDM process. RESULTS The clinical trial enrolled 922 patients (559 men [60.6%]; mean [SD] age, 71 [11] years) and 244 clinicians. A total of 463 patients were randomized to the intervention arm and 459 patients to the standard care arm. Participants in both arms reported high communication quality, high knowledge, and low decisional conflict, demonstrated low accuracy in their risk perception, and would similarly recommend the approach used in their encounter. Clinicians were significantly more satisfied after intervention encounters (400 of 453 encounters [88.3%] vs 277 of 448 encounters [61.8%]; adjusted relative risk, 1.49; 95% CI, 1.42-1.53). A total of 747 of 873 patients (85.6%) chose to start or continue receiving an anticoagulant medication. Patient involvement in decision-making (as assessed through video recordings of the encounters using the Observing Patient Involvement in Decision Making 12-item scale) scores were significantly higher in the intervention arm (mean [SD] score, 33.0 [10.8] points vs 29.1 [13.1] points, respectively; adjusted mean difference, 4.2 points; 95% CI, 2.8-5.6 points). No significant between-arm difference was found in encounter duration (mean [SD] duration, 32 [16] minutes in the intervention arm vs 31 [17] minutes in the standard care arm; adjusted mean between-arm difference, 1.1; 95% CI, −0.3 to 2.5 minutes). CONCLUSION AND RELEVANCE The use of an SDM encounter tool improved several measures of SDM quality and clinician satisfaction, with no significant effect on treatment decisions...
Background-Inflammation markers and metabolic syndrome (MetS) are associated with risk of congestive heart failure (CHF). We evaluated whether combining inflammation markers and MetS provided additive information for incident CHF and if incorporating inflammation markers to the MetS definition added prognostic information. Methods and Results-We studied 4017 men and women Ն65 years old, without baseline CHF or diabetes, participating in the Cardiovascular Health Study, an observational study with 12.2 years follow-up and 966 cases of incident CHF. Baseline "C-reactive protein (CRP)-MetS" or "interleukin (IL)-6 -MetS" were defined as presence of 3 out of 6 components, with elevated CRP (Ն3 mg/L) or IL-6 (Ն2.21 pg/mL) as a sixth component added to ATPIII criteria. Cox models adjusted for CHF risk factors and incident coronary disease were used to calculate hazard ratios for CHF. MetS and elevated inflammation markers were independently associated with CHF risk (hazard ratios, 95% CI:
Background-The left ventricles of both rabbits and humans express predominantly -myosin heavy chain (MHC).Transgenic (TG) rabbits expressing 40% ␣-MHC are protected against tachycardia-induced cardiomyopathy, but the normal amount of ␣-MHC expressed in humans is only 5% to 7% and its functional importance is questionable. This study was undertaken to identify a myofilament-based mechanism underlying tachycardia-induced cardiomyopathy protection and to extrapolate the impact of MHC isoform variation on myofilament function in human hearts. Methods and Results-Papillary muscle strips from TG rabbits expressing 40% (TG40) and 15% ␣-MHC (TG15) and from nontransgenic (NTG) controls expressing Ϸ100% -MHC (NTG40 and NTG15) were demembranated and calcium activated. Myofilament tension and calcium sensitivity were similar in TGs and respective NTGs. Force-clamp measurements revealed Ϸ50% higher power production in TG40 versus NTG40 (PϽ0.001) and Ϸ20% higher power in TG15 versus NTG15 (PϽ0.05). A characteristic of acto-myosin crossbridge kinetics, the "dip" frequency, was significantly higher in TG40 versus NTG40 (0.70Ϯ0.04 versus 0.39Ϯ0.09 Hz, PϽ0.01) but not in TG15 versus NTG15.The calculated crossbridge time-on was also significantly shorter in TG40 (102.3Ϯ14.2 ms) versus NTG40 (175.7Ϯ19.7 ms) but not in TG15 versus NTG15. Conclusions-The incorporation of 40% ␣-MHC leads to greater myofilament power production and more rapid crossbridge cycling, which facilitate ejection and relengthening during short cycle intervals, and thus protect against tachycardia-induced cardiomyopathy. Our results suggest, however, that, even when compared with the virtual absence of ␣-MHC in the failing heart, the 5% to 7% ␣-MHC content of the normal human heart has little if any functional significance. (Circ Heart Fail. 2009;2:334-341.)
BackgroundEnlargement of the proximal aorta is associated with aortic wall tissue remodeling, including fragmentation of the elastin fibers, increased synthesis of collagen, and calcification, all of which are associated with aortic wall stiffening. We hypothesized that the proximal aortic diameter (AoD) is associated with cardiovascular events in a community‐based cohort of blacks.Methods and ResultsWe investigated the associations between AoD and cardiovascular events among 3018 black participants (mean age, 55.9 years; 69% women) without past history of cardiovascular disease in the Jackson Heart Study. AoD was measured using echocardiography at the level of the sinuses of Valsalva at end diastole. Cardiovascular event was defined as incident myocardial infarction, fatal coronary artery disease, stroke, or heart failure hospitalization. Cox proportional hazards regression models were used to evaluate the association between baseline AoD and cardiovascular events. Over a median follow‐up of 8.3 years, there were 258 cardiovascular events (incident rate, 10.5 per 1000 person‐years). After adjustment for traditional risk factors, increased AoD was significantly associated with cardiovascular events (hazard ratio per 1‐cm increase, 1.72; 95% CI, 1.10–2.69; P<0.05). Participants in the top AoD quintile had a higher incidence of cardiovascular events compared to those not in the top quintile (hazard ratio, 1.47; 95% CI, 1.11–1.94; P<0.005) after adjustment for risk factors.ConclusionsGreater AoD was associated with an increased risk of cardiovascular events in a community‐based cohort of blacks. AoD may be useful as a predictor of incident cardiovascular events and further investigation is warranted.
OBJECTIVEWe evaluate associations of metabolic syndrome (MetS), C-reactive protein (CRP), and a CRP-incorporated definition of MetS (CRPMetS) with risk of all-cause mortality in a biracial population.RESEARCH DESIGN AND METHODSWe studied 23,998 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, an observational study of black and white adults ≥45 years old across the U.S. Elevated CRP was defined as ≥3 mg/L and MetS by the revised Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III; ATP III) criteria (three of five components). CRPMetS was defined as presence of three out of six components, with elevated CRP added to ATP III criteria as a sixth component. Cox models were used to calculate hazard ratios (HRs) for all-cause mortality, and population attributable risk (PAR) was calculated. Stratified analyses based on race and diabetes status were performed.RESULTSThere were 9,741 participants (41%) with MetS and 12,179 (51%) with CRPMetS at baseline. Over 4.8 years of follow-up, 2,050 participants died. After adjustment for multiple confounders, MetS, elevated CRP, and CRPMetS were each significantly associated with increased mortality risk (HRs 1.26 [95% CI 1.15–1.38], 1.55 [1.41–1.70], and 1.34 [1.22–1.48], respectively). The PAR was 9.5% for MetS, 18.1% for CRP, and 14.7% for CRPMetS. Associations of elevated CRP and of CRPMetS with mortality were significantly greater in whites than blacks, while no differences in associations were observed based on diabetes status.CONCLUSIONSBy definition, CRPMetS identifies more people at risk than MetS but still maintains a similar mortality risk. Incorporating CRP into the definition for MetS may be useful in identifying additional high-risk populations to target for prevention.
BackgroundTime to peak velocity (TPV) is an echocardiographic variable that can be easily measured and reflects a late peaking murmur, a classic physical finding suggesting severe aortic stenosis (AS). The aim of this study was to investigate the usefulness of TPV to evaluate AS severity.Methods and ResultsThis study included 700 AS patients, whose aortic valve area (AVA) was <1.5 cm2, and 200 control patients. The TPV was defined as the time from aortic valve opening to when the flow velocity across the aortic valve reaches its peak. AS severity was classified as follows: High gradient severe AS, mean pressure gradient ≥40 mm Hg and AVA index (AVAI) <0.6 cm2/m2; Low gradient severe AS, mean pressure gradient <40 mm Hg, AVAI <0.6 cm2/m2, and dimensionless index <0.25; moderate AS, mean pressure gradient <40 mm Hg, AVAI ≥0.6 cm2/m2. The area under the receiver operating characteristic curve of TPV to predict high gradient severe AS was 0.94 (95% CI: 0.92–0.97, P<0.001). TPV was significantly delayed in low gradient severe AS compared with moderate AS both in patients with preserved (102±13 ms versus 83±13 ms, P<0.001) and with reduced ejection fraction (110±18 ms versus 88±13 ms, P<0.001). Delayed TPV was associated with increased all‐cause mortality or need for aortic valve replacement after adjustment for confounders (hazard ratio for first quartile, reference is fourth quartile: 7.31, 95% CI 4.26–12.53, P<0.001).Conclusions TPV is useful to evaluate AS severity and predict poor prognosis of AS patients.
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