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Background: Noninvasive measurement of myocardial contractility (end-systolic wall stress-adjusted change in left ventricular ejection fraction from rest to exercise [ΔLVEF - ΔESS]) predicts heart failure, subnormal LVEFrest, and sudden death in asymptomatic patients with chronic severe aortic regurgitation (AR). Here we assess the relation of preoperative ΔLVEF - ΔESS to survival after aortic valve replacement (AVR)., Methods: Patients who underwent AVR for chronic, isolated, pure severe AR (n = 66) were followed for 13.0 ± 6.4 event-free years. Preoperative ΔLVEF - ΔESS (from combined echocardiographic and radionuclide cineangiographic data) enabled cohort stratification into 3 terciles (-1 to -11% [normal or mild] contractility deficit, -12 to -16% [moderate], and ≤-17% [severe], identical with segregation in our earlier study) to relate preoperative contractility to postoperative survival and to age- and gender-matched US census data., Results: Since AVR, 22 patients died (average annual risk [AAR] for all-cause mortality for the entire co hort = 3.15%). Preoperative ΔLVEF - ΔESS predicted postoperative survival (p = 0.009, log rank test). By contractility terciles, all-cause AARs were 1.44, 2.58, and 6.40%. Survival was lower than among US census comparators (p < 0.02), but the "mild" tercile was indistinguishable from census data (p = ns). By multivariable Cox regression, survival prediction by pre-AVR ΔLVEF - ΔESS was independent of, and superior to, prediction by age at surgery, gender, preoperative functional class, LVEFrest, LVEFexercise, change in LVEFrest to exercise, and LV diastolic or systolic dimensions (p ≤ 0.01, pre-AVR ΔLVEF - ΔESS vs. other covariates)., Conclusion: In severe AR, preoperative contractility predicts post-AVR survival and may be prognostically superior to clinical, geometric and performance descriptors, potentially impacting on patient selection for surgery., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Objectives: The aim of this study was to examine the impact of beta-blockade on cardiac events among patients with initially asymptomatic chronic severe nonischemic mitral valve regurgitation (MR)., Methods: Data from 52 consecutive patients in our prospective natural history study of isolated chronic severe nonischemic MR were assessed post hoc over 19 years to examine the relation of chronic beta-blockade use to subsequent cardiac events (death or indications for mitral valve surgery, MVS). At entry, all patients were free of surgical indications; 9 received beta-blockers. Cardiac event rate differences were analyzed by Kaplan-Meier log rank comparison., Results: During follow-up, cardiac events included sudden death (1), heart failure (8), atrial fibrillation (6), left ventricular dimensions at systole ≥4.5 cm (11), left ventricular ejection fraction <60% (6), right ventricular ejection fraction <35% (2), and a combination of cardiac events (7). The cardiac event risk was 4-fold higher among patients receiving beta-blockers (average annual risk = 60.6%) versus those not receiving beta-blockers (average annual risk = 15.2%; p = 0.001). These effects remained statistically significant (p = 0.005) when analysis was adjusted for other baseline covariates., Conclusions: Beta-blockade appears to confer an increased risk of sudden cardiac death or indications for MVS among patients with chronic severe nonischemic MR. Randomized trials are needed to confirm these findings., (© 2017 S. Karger AG, Basel.)

Objectives: In the Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT), slowing of the heart rate with ivabradine reduced cardiovascular death or heart failure hospitalizations among patients with systolic chronic heart failure (CHF). Subsequently, in the Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients with Coronary Artery Disease (SIGNIFY) slowing of the heart rate in patients without CHF provided no benefit for cardiovascular death or nonfatal myocardial infarction (primary composite end point), with secondary analyses suggesting possible harm in the angina subgroup. Therefore, we examined the impact of ivabradine in the patients with CHF plus angina in SHIFT., Methods: SHIFT enrolled adults with stable, symptomatic CHF, a left ventricular ejection fraction ≤35% and a sinus rhythm with a resting heart rate ≥70 bpm. Outcomes were the SHIFT and SIGNIFY primary composite end points and their components., Results: Of 6,505 patients in SHIFT, 2,220 (34%) reported angina at randomization. Ivabradine numerically, but not significantly, reduced the SIGNIFY primary composite end point by 8, 11 and 11% in the SHIFT angina subgroup, nonangina subgroup and overall population, respectively. Ivabradine also reduced the SHIFT primary composite end point in all 3 subgroups., Conclusions: In SHIFT, ivabradine showed consistent reduction of cardiovascular outcomes in patients with CHF; similar results were seen in the subgroup of SHIFT patients with angina., (© 2016 S. Karger AG, Basel.)

Objectives: We explored the prescription of β-blockers with ivabradine in patients with systolic heart failure, focusing on the most frequently coprescribed β-blocker, carvedilol., Methods: We analyzed outcomes in SHIFT patients with systolic heart failure who were prescribed β-blockers (carvedilol, bisoprolol, metoprolol, or nebivolol) with ivabradine or placebo. Analysis was by intention to treat in patients prescribed a β-blocker at the time of the event., Results: Data were available for 2,596 patients receiving carvedilol, 1,483 bisoprolol, 1,424 metoprolol, and 197 nebivolol. Mean treatment duration was 19 months. There was no difference in the effect of ivabradine on the primary composite endpoint of cardiovascular death or heart failure hospitalization between the various β-blockers [hazard ratios (HR) for risk reduction, 0.75-0.89; p for interaction=0.86]. Patients prescribed carvedilol with ivabradine had lower rates of primary composite endpoint (HR 0.80, 95% CI: 0.68-0.94), heart failure hospitalization (HR 0.73, 95% CI: 0.61-0.88), and cardiovascular hospitalization (HR 0.80, 95% CI: 0.69-0.92) versus carvedilol with placebo. The dosage of carvedilol had no detectable effect and there were no unexpected safety issues., Conclusions: Whatever β-blocker was coprescribed with ivabradine, there were improvements in cardiovascular outcomes in patients with systolic heart failure, especially with the most prescribed β-blocker--carvedilol., (© 2015 S. Karger AG, Basel.)

It has long been known that life span is inversely related to resting heart rate in most organisms. This association between heart rate and survival has been attributed to the metabolic rate, which is greater in smaller animals and is directly associated with heart rate. Studies have shown that heart rate is related to survival in apparently healthy individuals and in patients with different underlying cardiovascular diseases. A decrease in heart rate due to therapeutic interventions may result in an increase in survival. However, there are many factors regulating heart rate, and it is quite plausible that these may independently affect life expectancy. Nonetheless, a fast heart rate itself affects the cardiovascular system in multiple ways (it increases ventricular work, myocardial oxygen consumption, endothelial stress, aortic/arterial stiffness, decreases myocardial oxygen supply, other) which, in turn, may affect survival. In this brief review, the effects of heart rate on the heart, arterial system and survival will be discussed., (© 2015 S. Karger AG, Basel.)

Objectives: The relation of indirect vasodilator use to cardiac events (CE) is undefined for chronic severe nonischemic mitral regurgitation (MR). The aim of this study was to resolve this knowledge deficiency., Methods: Data from 52 consecutive patients in our prospective natural history study with isolated chronic severe nonischemic MR were assessed post hoc over 19 years to examine the relation of indirect vasodilator use to subsequent CE (death or indications for valve surgery). At entry, no patient had surgical indications, 14% had hypertension (HTN) and 7 chronically received vasodilators (5 angiotensin-converting enzyme inhibitor, 1 receptor blocker and 1 α-adrenergic blocker). CE differences were assessed by log-rank comparison of Kaplan-Meier curves., Results: During follow-up, CE included sudden death (1 patient), heart failure (7 patients), atrial fibrillation (6 patients), left ventricular (LV) systolic dimension >4.5 cm (12 patients), LV ejection fraction (EF) <60% (7 patients), right ventricular EF <35% (2 patients) and combination CE (7 patients). Overall, vasodilator use did not predict CE (not significant). However, patients without HTN had higher CE rates with vasodilators than without (p = 0.007), while those with HTN and vasodilators had lower CE rates than those without vasodilators (p = 0.04)., Conclusion: Vasodilator use appears to confer no survival benefit in patients with chronic severe MR. The small number of patients with HTN precludes conclusions about modulation of vasodilator effect by HTN. Randomized trials are needed to conclusively evaluate this association.

Despite an early invasive strategy and the use of dual antiplatelet therapy, patients with acute coronary syndrome (ACS) continue to be at substantial risk for recurrent ischemic events. It is believed that this risk is, at least in part, due to an intrinsic coagulation pathway that remains activated for a prolonged period after ACS. Earlier studies using warfarin showed a reduction in ischemic events, but the overall benefits were offset by increased bleeding complications. Recently, there has been increased interest in the potential role of new oral anticoagulants, some of which target factor Xa, after ACS. Factor Xa is important for the coagulation pathway and also plays a role in cellular proliferation and inflammation. It may thus be an attractive target for therapeutic intervention in ACS. Recently, various oral factor Xa inhibitors have been studied as potential treatment options for ACS. This review will focus on currently available data to evaluate the possible role of factor Xa inhibitors in the management of patients with ACS.

Background: Nonsustained ventricular tachycardia (VT), frequent in unoperated severe mitral regurgitation (MR), confers mortality risk [sudden death (SD) and cardiac death (CD)]. The prognostic value of VT after mitral valve surgery (MVS) is unknown; we aimed to define this prognostic value and to assess its modulation by left (LV) and/or right (RV) ventricular ejection fraction (EF) for mortality after MVS., Methods: In 57 patients (53% females, aged 58 ± 12 years) with severe MR prospectively followed before and after MVS, we performed 24-hour ambulatory electrocardiograms approximately annually. LVEF and RVEF were determined within 1 year after MVS by radionuclide cineangiography., Results: During 9.52 ± 3.49 endpoint-free follow-up years, late postoperative CD occurred in 11 patients (7 SD, 4 heart failures). In univariable analysis, >1 VT episode after MVS predicted SD (p < 0.01) and CD (SD or heart failure; p < 0.04). Subnormal postoperative RVEF predicted CD (p < 0.04). When adjusted for preoperative age, gender, etiology or antiarrhythmics, both postoperative VT and RVEF predicted CD (p ≤ 0.05). When postoperative VT and RVEF were both in the multivariable model, only subnormal RVEF predicted CD (p < 0.04). Among those with normal RVEF, VT >1 episode predicted SD (p = 0.03)., Conclusion: Postoperative VT and subnormal RVEF predict late postoperative deaths in nonischemic MR. Their assessment may aid patient management., (Copyright © 2013 S. Karger AG, Basel.)

Off-pump coronary artery bypass (OPCAB) has gained increasing acceptance with potential benefits for high-risk elderly patients. We report a surgeon's operative outcomes in octogenarians with an OPCAB program. Retrospective, intention-to-treat analysis of 97 consecutive octogenarians who underwent coronary bypass by a single surgeon between 1997 and 2001 before and after initiation of a multi-vessel OPCAB program was performed. OPCAB was attempted in all octogenarians. The OPCAB cohort had higher serum creatinine (OPCAB vs. pre-OPCAB: 1.30 ± 0.79 mg/dl vs. 1.08 ± 0.27, p = 0.04) and ejection fractions (52 ± 14% vs. 45 ± 11%, p = 0.02) than the pre-OPCAB cohort. The OPCAB group was more likely to require urgent/emergency surgery (63 vs. 40%, p = 0.04) and to have chronic renal insufficiency (18 vs. 3%, p = 0.05). After programmatic change to OPCAB, significant postoperative improvements were observed in the length of hospital stay (17 ± 19 vs. 8 ± 4 days, p < 0.01), duration of inotropic requirement (47 ± 70 vs. 18 ± 39 h, p < 0.04), duration of ventilator support (51 ± 54 vs. 16 ± 27 h, p < 0.01) and incidence of tracheostomy (16 vs. 3%, p < 0.02). In-hospital mortalities (3.2 vs. 2.7%), strokes (3 per group) and 5-year survival did not differ significantly (57 vs. 67%, p = 0.50, NS). Despite some higher preoperative risks, the OPCAB program demonstrated clinical benefits in octogenarians but no advantage in hospital-mortality or long-term survival., (Copyright © 2013 S. Karger AG, Basel.)

A metamorphosis in the etiology of valvular heart disease (VHD) has occurred over the last 6 decades. In this review, the factors contributing to this metamorphosis, the common causes of VHD today, the relationship of valvular calcification to atherosclerosis and the interrelationship of VHD with other systems/organs are presented., (Copyright © 2013 S. Karger AG, Basel.)

Background: Anxiety and insomnia are associated with cardiovascular (CV) symptoms. We assessed whether the relation between anxiety and CV symptoms is modulated by insomnia., Methods: Independently living women (n = 1,440; mean age = 59.36 +/- 6.53 years) were recruited by cluster sampling technique. We obtained data on demographic characteristics, health beliefs, access to health care, CV symptoms, sleep, stress and anxiety levels., Results: Overall, 56% of the sample reported insomnia; 46% reported CV symptoms, and 54% were highly anxious. There was a greater likelihood for highly anxious women and those experiencing insomnia to report CV symptoms (r(s) = 0.31* and r(s) = 0.32*, respectively). In logistic regression analysis, the adjusted odds ratios for reporting CV symptoms were 1.39 for patients with insomnia and 2.79 for those with anxiety. With control for insomnia, we observed a 3-fold reduction in the magnitude of the association between anxiety and CV symptoms (r(p) = 0.09*). Stepwise adjustments for sociodemographic factors, CV risk markers, and factors anchoring health beliefs and access to health care showed lesser impact on the relationships. With simultaneous control for those covariates, the correlation was r(p) = 0.13*; * p < 0.01., Conclusion: The association of CV symptoms with anxiety is partly accounted for by insomnia.

Objectives: The antianginal and anti-ischemic efficacy of ivabradine has been demonstrated in large-scale trials. Pooling trial data allowed for subpopulation analyses of ivabradine's antianginal efficacy., Methods: Data on the frequency of angina attacks, short-acting nitrate consumption, and heart rate were pooled from 5 randomized trials in patients with stable angina pectoris receiving 5, 7.5, or 10 mg of ivabradine b.i.d. for 3 or 4 months. The subpopulations were defined according to age, sex, disease characteristics, and comorbidities (severity of angina, history of myocardial infarction, cerebrovascular disease, revascularization status, diabetes, asthma/chronic obstructive pulmonary disease, or peripheral vascular disease)., Results: Efficacy data were available for 2,425 patients (full analysis set), in whom ivabradine reduced the frequency of diary-based angina attacks by 59.4% and nitrate consumption by 53.7%. All subpopulations experienced 51-70% reductions in the frequency of angina attacks, with similar reductions for the other parameters studied. Ivabradine's efficacy was maintained in the presence of different comorbidities. In the safety set, ivabradine reduced heart rate by 14.5%. Ivabradine had a good safety and tolerability profile in all the subpopulations assessed., Conclusions: The antianginal efficacy of ivabradine was consistent across all the subpopulations analyzed, independent of the severity of angina and the presence of a comorbidity., (Copyright 2009 S. Karger AG, Basel.)

Objectives: In aortic regurgitation (AR), fibronectin (FN) expression is upregulated. This study sought to determine signal transduction pathways involved in upregulation of FN expression in AR., Methods: Cardiac fibroblasts (CF) from rabbits with surgically induced AR and matched controls (NL) were cultured and assayed for FN expression and kinase activity with and without inhibitors of kinases JNK, p38 mitogen-activated protein kinase (MAPK) and extracellular response kinase (ERK). NL CF also were subjected to cyclic strain mimicking AR for 24 h in culture with and without inhibitors., Results: AR CF exhibited 2.9-fold greater c-Jun phosphorylation (p < 0.01) and 1.5- to 2-fold greater ATF2 phosphorylation (p < 0.05-0.01) than NL. JNK and p38MAPK inhibition reduced c-Jun and ATF2 phosphorylation to NL; ERK inhibition had no effect. FN mRNA expression was similar in pattern to kinase activities. Cyclic strain in NL CF increased c-Jun phosphorylation 2-fold versus unstrained controls (p < 0.005). This was suppressed by inhibition of JNK but not p38MAPK., Conclusion: FN expression in response to the acute mechanical strain resembling AR is upregulated primarily via JNK. However, in chronic AR both JNK and p38MAPK are involved. These signaling pathways represent potential therapeutic targets for normalizing extracellular matrix (ECM) composition and contractile force transmission, believed to be related to ECM composition/organization, in AR., (Copyright 2009 S. Karger AG, Basel.)

Objectives: Myocardial fibrosis in experimental aortic regurgitation (AR) features abnormal fibronectin with normal collagen content, but the relevant degradative processes have not been assessed., Methods: To elucidate these degradative processes, mRNA (Northern) and protein levels (Western) of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), as well as MMP activity (zymography), were measured in cardiac fibroblasts (CF) from New Zealand white rabbits with experimental AR paired with normals (NL). Collagen and fibronectin were quantified by immunohistochemical staining., Results: In AR CF versus NL CF, MMP-2 and -14 mRNA and protein were increased (both p < 0.005), while TIMPs 1-3 were slightly decreased (p < 0.05-0.005; TIMP-4 undetectable). Gelatinase activity in AR CF was 1.7 times that in NL CF (p < 0.005); fibronectinase activity was unaffected. The Jun N-terminal kinase (JNK) inhibitor SP600125 suppressed MMP-2 protein (0.4-fold, p < 0.05) and mRNA (0.7-fold, p < 0.005) in AR CF; MMP-2 levels in NL CF were unaffected. AR MMP-9 mRNA, protein and activity were low and indistinguishable from NL. In left ventricular tissue, fibronectin was increased 1.9-fold (AR vs. NL, p < 0.05). Total AR collagen was indistinguishable from NL, but the collagen III to collagen I isoform ratio decreased (0.4-fold, p < 0.05)., Conclusions: Collagen is relatively deficient in AR fibrosis, due at least in part to upregulated MMPs and downregulated TIMPs; fibronectinase is unaltered. JNK-dependent regulation may stimulate both MMP-2 and fibronectin expression in AR, providing a potential therapeutic target., (Copyright (c) 2009 S. Karger AG, Basel.)

Cell therapies hold the potential for suppression, modification, or cure of disease. Several unique challenges have been recognized as this field has developed. Many of these involve considerations of trial design. This paper summarizes the discussion and suggestions constructed during the 8th Cardiovascular Clinical Trialists Workshop, a meeting involving cardiovascular clinical trialists, biostatisticians, National Institutes of Health scientists, European and United States regulators, and pharmaceutical industry scientists. Investigators must adapt research methods to accommodate the scientific advances associated with cell therapy. Safety and efficacy of cell therapy for cardiovascular indications should be evaluated with the same degree of scientific rigor required of pharmacologic agents, and the same fundamental regulatory requirements and scientific processes apply to both. Clinical trials for these indications should also meet standards similar to those set for drug therapies. Safety should be determined throughout development, dose responsiveness should be established and, while surrogate endpoints are important development tools, the ultimate demonstration of efficacy must rely on clinical benefit. The establishment of a global safety database for cell therapy would significantly advance the field. Efforts to discover innovative therapies must be balanced by a commitment to comprehensively evaluate the safety and efficacy of the new treatments., (Copyright 2007 S. Karger AG, Basel.)

Objectives: Hypotension is common immediately following cardiopulmonary bypass. Experimentally, MTR-105 (S-ethylisothiuronium diethylphosphate), a fast-acting synthetic nitric oxide synthase inhibitor, rapidly increases blood pressure. The purpose of the current study was to assess the influence of MTR-105 on hemodynamics early after cardiopulmonary bypass in patients undergoing open-heart surgery., Methods: Thirty-six patients with an ejection fraction >50% undergoing open-heart surgery were randomly assigned to either 50 microg kg(-1) min(-1) MTR-105 (M50, n = 12), 10 microg kg(-1) min(-1) MTR-105 (M10, n = 12) or buffered phosphate solution (placebo control, n = 12). Half suffered from atrial fibrillation and 75% had severe tricuspid regurgitation. Patients received the drug for 6 h after cross-clamp removal. Hemodynamic variables were measured before drug administration until 24 h after operation. Adverse events were recorded from study drug initiation through 30 days after the operation., Results: Compared with control, both MTR-105 doses were associated with an immediate increase in systemic blood pressure (16%) and systemic vascular resistance and a decrease in cardiac index. Half-life time of MTR-105 was calculated to be 4.1 +/- 0.8 h (M10) and 4.45 +/- 0.92 h (M50). Three patients died during hospitalization, unrelated to the study medication., Conclusions: At the doses employed, MTR-105 appears hemodynamically active in increasing both blood pressures., (Copyright 2008 S. Karger AG, Basel.)

Among patients with chronic nonischemic mitral regurgitation (MR), high short-term mortality risk can be identified by left (LV) and/or right ventricular (RV) ejection fraction (EF) criteria (LVEF 20%, MVR significantly improved survival versus medical treatment (rest: p < 0.0001, exercise: p = 0.0003). In high risk MR patients, MVR improves survival; preoperative RV performance can define subgroups with different long-term postoperative survival., (Copyright 2000 S. Karger AG, Basel)

Myocardial fibrosis and myocyte degeneration have been reported in patients with chronic aortic regurgitation (AR), and may be related to the pathophysiology of congestive heart failure (CHF) in this disease. To define the relationship between myocardial histopathologic variations and CHF in chronic AR, we performed gross and microscopic evaluations of postmortem tissue from a rabbit model of chronic AR manifesting left ventricular (LV) responses to AR similar to those in humans. Moderate-to-severe chronic AR (echocardiographic regurgitant fraction = 52 +/- 13%) was induced by closed-chest aortic valve perforation in 11 New Zealand White rabbits; 5 control rabbits were sham operated. Six of the 11 AR rabbits died 1.5 +/- 0.8 years (range 0.6-2.8 years) after AR induction; all 6 had gross and histologic anatomic evidence of CHF at necropsy. The remaining 5 AR rabbits survived until sacrifice at 2.9 +/- 0.1 years of AR; none had pathologic evidence of CHF. Cardiac hypertrophy and the extent of LV fibrosis and myocyte necrosis all were greatest among the 6 AR CHF rabbits. No inflammatory response was apparent in any animal. Moderate-to-severe chronic experimental AR frequently results in CHF which is strongly associated with myocardial fibrosis and necrosis, without evidence of inflammation. These histopathologic variations may be pathophysiologically related to CHF development.

We recently demonstrated dynamic alterations in protein turnover 3 days and 1 month after surgical induction of aortic regurgitation (AR). To characterize protein synthesis and degradation during the long-term plateau phase, we performed [3H]-leucine infusion 2.5 years after induction of AR in 10 New Zealand White rabbits and 12 sham-operated controls. Protein fractional synthesis rates were obtained by analyses of plasma and protein hydrolysates, growth rates from protein concentration and heart weight measurements, and degradation rates by subtraction of growth from synthesis rates. AR (regurgitant fraction 25 +/- 11%) caused a 57% increase in left ventricular (LV) weight in comparison with controls (7.4 +/- 1.7 vs. 4.7 +/- 0.6 g, p < 0.001) and no evidence of heart failure. Although concentrations of total cardiac protein, myosin heavy chain and actin were similar, the enlarged AR hearts had increased amounts of total cardiac protein (1,009 +/- 312 vs. 682 +/- 120 mg/LV, p < 0.05), myosin heavy chain (148 +/- 91 vs. 81 +/- 29 mg/LV, p < 0.05), and actin (73 +/- 42 vs. 44 +/- 16 mg/LV, p < 0.06). Individual protein fractional synthesis and degradation rates were closely balanced. However, myosin fractional synthesis rates were 152% (p < 0.01) greater than those of total cardiac protein in AR animals, while only 52% (p < 0.05) greater in controls (AR vs. controls, p = 0.05). Variations in actin turnover between AR and control animals did not attain statistical significance. Myosin and actin fractional synthesis rates correlated closely in AR rabbits (R = 0.81, p < 0.02), but not among controls (R = 0.41, NS). Thus, selective alterations in myofibrillar protein turnover contribute to the maintenance of increased myofibrillar protein content in the 'compensatory' LV hypertrophy of chronic AR.

We recently demonstrated that total cardiac protein and myosin heavy chain fractional synthesis rates were not increased during the progressive cardiac hypertrophy that occurred 1 month following induction of aortic regurgitation. The increase in total cardiac protein and myosin heavy chain observed after 1 month of chronic volume overload was caused by a decrease in protein fractional degradation rates. The objective of the present study was to determine in vivo the relative contributions of protein synthesis and degradation of a variety of individual myofibrillar protein constituents, other than myosin heavy chain, to the left ventricular hypertrophic response to chronic aortic regurgitation. Intravenous infusions of [3H]-leucine were administered 3 days and 1 month following surgical induction of aortic regurgitation and sham operation in rabbits, and actin, myosin light chains 1 and 2, alpha-actinin and desmin fractional synthesis rates were obtained by analysis of plasma and protein hydrolysate data using [14C]-dansyl chloride assays. Individual myofibrillar protein growth rates were determined from protein concentration and serial echocardiographic and postmortem left ventricular weight measurements; protein degradation rates were determined by subtraction of growth rates from synthesis rates. Individual myofibrillar protein content increased most rapidly during the 1st week and progressively increased at a slower rate between 1 week and 1 month, in parallel with increases in left ventricular weight. In comparison with sham-operated controls, individual myofibrillar protein fractional synthesis rates were consistently increased at 3 days but not at 1 month. Progressive myocyte hypertrophy occurring at 1 month was caused by a decrease in myofibrillar protein fractional degradation rates. Increased myofibrillar protein synthesis contributed only to the early phase of myocyte hypertrophy while progressive hypertrophy in chronic aortic regurgitation was due to suppression of myofibrillar protein degradation.

Pulmonary artery pressures in patients with aortic stenosis have been related to postoperative prognosis and surgical risk. However, while right- and left-heart pressures should be measured simultaneously, a catheter lying across the stenotic aortic valve might alter left- and right-heart pressures. To assess this phenomenon, right- and left-heart pressures were recorded before and after retrograde crossing of the aortic valve in 51 patients (30 patients with and 21 without aortic stenosis). In aortic stenosis, the mean pulmonary artery pressure increased (p less than 0.001) after transaortic valvular pressure catheter placement (average 4 mm Hg, peak 19 mm Hg); in the absence of aortic stenosis, the mean pulmonary artery pressure did not change (average 0 mm Hg; NS). A similar response was noted for the mean pulmonary capillary wedge pressure. Hemodynamic changes did not correlate with the severity of aortic stenosis or with left ventricular performance. Right-heart pressures should be determined without transaortic valvular catheter in place, if accurate interpretation of the hemodynamic effects of aortic stenosis is to be achieved.

To establish the etiology of strokes related to the anticardiolipin antibody (Acla) syndrome and to determine the relationship of valvular heart disease and stroke in the presence of the Acla, clinical and objective characteristics of 21 patients with Acla, focal cerebral ischemic events were retrospectively analyzed. Twelve (86%) of 14 patients with stroke and 3 (42%) of 7 patients with non-stroke cerebral ischemic events had echocardiographic evidence of left-sided valvular abnormalities. Features characteristic of cardioembolic stroke were present in 12 (86%) of the 14 patients with stroke. The strength of the association between valvular disease and stroke, combined with the clinical and radiologic features noted, suggest that strokes related to the Acla syndrome typically are embolic, from a cardiac source.