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Transcatheter aortic valve replacement (TAVR) has become a mainstay treatment for severe aortic stenosis and is increasingly used for veterans, producing excellent short-term outcomes. There is a paucity of long-term outcome data after TAVR in the veteran population.We examined consecutive patients who underwent TAVR at a single Veterans Affairs medical center through 2019. Baseline characteristics, echocardiographic and angiographic variables, and clinical outcomes were abstracted. All-cause mortality was the primary outcome of interest. Factors associated with all-cause mortality and cardiac-specific mortality, including the presence of significant non-revascularized coronary artery disease (CAD), were assessed with multivariable regression and competing-risk analyses.The 189 consecutive patients enrolled (mean age, 76.6 ± 8.4 years) had a median Society of Thoracic Surgeons (STS) score of 6.0 (interquartile range [IQR], 4.0-8.5). After a maximum follow-up of 7.5 years, 71 (37.6%) deaths occurred, of which 76% had a cardiac cause. Median overall survival was 3.55 years (95% confidence interval [CI], 3.21-5.30); significant graded differences were observed across STS risk subgroups (P.001). After multivariable adjustment, CAD was significantly associated with cardiac mortality (hazard ratio [HR], 2.6; 95% CI, 1.3-5.3) and all-cause mortality (HR, 2.2; 95% CI, 1.1-4.3). Other independent variables associated with all-cause mortality included age (P=.01), baseline creatinine (P.01), and chronic obstructive pulmonary disease (P=.03). Baseline ejection fraction (P=.04), age (P.01), creatinine (P=.02), and vascular disease (P=.04) were independently associated with cardiac-specific mortality.Long-term survival of veterans after TAVR is comparable to that of their non-veteran counterparts. Significant CAD, along with age and select comorbidities, was associated with poorer survival.

Echocardiograms are the second most frequently utilized cardiac test after electrocardiograms and are most commonly ordered by noncardiology providers. Echocardiogram reports are designed to communicate a comprehensive interpretation of cardiac function; however, it is not known how well these reports are understood by ordering providers. In order to identify gaps in understanding and target potential areas for improvement, we developed a questionnaire testing various topics reported on a standard transthoracic echocardiogram report. This questionnaire was administered to general medicine and cardiology trainees and attending physicians at 2 large academic institutions. Questionnaire response rate was 81%. There were several topics that were not well understood by general providers; these included viability of an akinetic region, pulmonary artery systolic pressure, left ventricular filling pressure, recognition of abnormal structures, and method of identifying of intracardiac thrombus. In conclusion, strategies such as improved communication techniques and adjustment of reporting format should be implemented to increase the clinical value of the echocardiogram.

Surgery remains the standard of care, but transcatheter aortic valve replacement is an emerging, viable option for some.

Objective Our objective was to evaluate the natural history of moderate aortic stenosis in veterans—a unique patient population with significant comorbidities. Methods We retrospectively reviewed the records of all patients who underwent echocardiography at a single veterans affairs hospital during 2006. We identified consecutive patients who had moderate aortic stenosis as indicated by a mean transaortic gradient of 25 to 40 mm Hg, peak aortic jet velocity of 3 to 4 m/s, or aortic valve area of 1.0 to 1.5 cm 2 . The primary end point was defined as survival without aortic valve replacement. Results Of the 104 patients (mean age, 74 ± 10 years), 49% had diabetes, 21% had peripheral vascular disease, 21% were current smokers, 18% had chronic obstructive pulmonary disease, 60% had coronary artery disease, 89% had hypertension, and 31% had a body mass index of 30 kg/m 2 or more. Mean ejection fraction was 49% ± 12%. During the mean follow-up period of 22 months (range, 1-67 months), 30% of patients underwent aortic valve replacement—26% for symptomatic severe aortic stenosis and 4% concomitantly with coronary artery bypass grafting as the primary indicated operation—and 61% died. Event-free survivals were 48%, 24%, and 15% at 1, 3, and 5 years, respectively. Conclusions Our cohort of military veteran patients had significant comorbidities. Event-free survival for such patients who have moderate aortic stenosis is significantly lower than previously reported data suggest. Within this unique group of patients, identifying factors that accelerate the progression of moderate aortic stenosis would help surgeons select patients who may benefit from early aortic valve replacement for moderate aortic stenosis.

Iatrogenic aortic valve leaflet perforation and aorto-right atrial fistula are rare adverse events of transcatheter interventions and transseptal radiofrequency ablations, respectively. We present the case of a 62-year-old man who experienced acute, severe aortic insufficiency as a result of leaflet entrapment by a septal occluder device during attempted percutaneous closure of an iatrogenic aorto-right atrial fistula. This rare adverse event emphasizes the need for a thorough understanding of cardiac anatomy to minimize transcatheter adverse events and to recognize and treat them appropriately when they occur.

Objectives This paper describes the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial and its effect on risk factors. Background Most cardiovascular clinical trials test a single intervention. The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention in patients with stable coronary disease. Methods All patients, regardless of treatment assignment, received equivalent lifestyle and pharmacologic interventions for secondary prevention. Most medications were provided at no cost. Therapy was administered by nurse case managers according to protocols designed to achieve predefined lifestyle and risk factor goals. Results The patients (n = 2,287) were followed for 4.6 years. There were no significant differences between treatment groups in proportion of patients achieving therapeutic goals. The proportion of smokers decreased from 23% to 19% (p = 0.025), those who reported Conclusions Secondary prevention was applied equally and intensively to both treatment groups in the COURAGE trial by nurse case managers with treatment protocols and resulted in significant improvement in risk factors. Optimal medical therapy in the COURAGE trial provides an effective model for secondary prevention among patients with chronic coronary disease. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657)

We examined factors affecting the choice of surgical versus medical treatment of severe aortic stenosis and evaluated associated patient survival.We retrospectively reviewed data from all patients diagnosed with severe aortic stenosis at a Veterans Affairs medical facility between January 1997 and April 2008.Of 345 patients with severe aortic stenosis, 260 (75%) underwent surgical evaluation, and 205 (59%) underwent aortic valve replacement (AVR). The patient's decision to decline surgical referral or AVR (n = 47) and severe comorbidities (n = 34) were the top two reasons for medical treatment rather than AVR. The AVR group was younger (69.5 +/- 9.6 years versus 75.7 +/- 8.6 years; p0.001) and had a higher prevalence of symptoms (96% versus 71%; p0.001) than the medical group. The medical group had a lower cardiac ejection fraction (0.42 +/- 0.15 versus 0.50 +/- 0.12; p0.001) and was less likely to be independent in activities of daily living (64% versus 74%). The AVR group had higher survival rates than the medical patients at 1 year (92% versus 65%), 3 years (85% versus 29%), and 5 years (73% versus 16%; log-rank test p0.0001). Valve replacement was independently associated with decreased mortality (hazard ratio, 0.17; 95% confidence interval, 0.10 to 0.27; p0.0001).The management of severe aortic stenosis in veterans is sometimes limited to medical evaluation and treatment. Surgeons should be involved in the complex process of risk assessment, to select patients with severe aortic stenosis who would benefit from the survival advantage associated with AVR.

OBJECTIVESWe wished to determine the effect of post-infarct management strategy on event rates (death or recurrent nonfatal myocardial infarction [MI]) in patients who evolved non–Q-wave MI (NQMI) following thrombolytic therapy.BACKGROUNDPatients who evolve NQMI following thrombolytic therapy are often considered to be at high risk and are frequently managed with routine early invasive testing despite a lack of data supporting improved outcome.METHODSThe Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) study included 115 patients who evolved NQMI following thrombolytic therapy. We compared the event rates in patients randomized to routine early coronary angiography with those in patients randomized to a conservative strategy of noninvasive functional assessment, with angiography reserved for patients with spontaneous or induced ischemia.RESULTSDuring an average follow-up of 23 months, 19 of 58 patients (33%) randomized to the invasive management strategy died or suffered recurrent nonfatal MI, compared with 11 of 57 patients (19%) randomized to the conservative strategy (p = 0.152). Equivalent numbers of patients were subjected to revascularization (percutaneous transluminal coronary angioplasty or coronary artery bypass graft). There were more deaths in the invasive management group than in the conservative management group (11 vs. 2). Excess deaths could not be attributed to periprocedural mortality.CONCLUSIONSOverall event rates (death or recurrent nonfatal MI) are comparable with conservative and invasive strategies in patients who evolve NQMI following thrombolytic therapy. Mortality rate in patients managed conservatively is low (3.5%), and routine invasive management may be associated with an increased risk of death.

This article discusses the recognition and management of major disorders of the tricuspid valve in the context of altered anatomy and physiology. First, selected congenital lesions in which the tricuspid valve is an important, often primary component of the complex are discussed, then acquired causes of valvar insufficiency and finally restricted inflow are discussed. Ultrasound imaging and Doppler flow interrogation allow bedside analysis of the pathoanatomy and altered physiology, correlate beautifully with careful physical examination, and provide insight into cause and severity that are important factors in clinical decision making.

Objectives. We sought to evaluate the comparative accuracy of myocardial contrast echocardiography (MCE), quantitative rest-redistribution thallium-201 (Tl-201) tomography and low and high dose (up to 40 μg/kg body weight per min) dobutamine echocardiography (DE) in identifying myocardial hibernation.Background. Myocardial contrast echocardiography can assess myocardial perfusion and may therefore be useful in predicting myocardial hibernation. However, its accuracy in comparison to myocardial perfusion scintigraphy and to that of high dose DE remains to be investigated.Methods. Eighteen patients (aged [±SD] 57 ± 10 years) with stable coronary artery disease and ventricular dysfunction underwent the above three modalities before coronary revascularization. Myocardial contrast echocardiography was achieved with intracoronary Albunex. Rest echocardiographic and Tl-201 studies were repeated ≥6 weeks after revascularization.Results. Of 109 revascularized segments with severe dysfunction, 46 (42%) improved. Left ventricular ejection fraction increased from 38 ± 14% to 45 ± 13% at follow-up (p = 0.003). Rest Tl-201 uptake and the ratio of peak contrast intensity of dysfunctional to normal segments with MCE were higher (p < 0.01) in segments that recovered function compared with those that did not. Myocardial contrast echocardiography, thallium scintigraphy and any contractile reserve during DE had a similar sensitivity (89% to 91%) with a lower specificity (43% to 66%) for recovery of function. A biphasic response during DE was the most specific (83%) and the least sensitive (68%) (p < 0.01). The best concordance with MCE was Tl-201 (80%, kappa 0.57). Changes in ejection fraction after revascularization related significantly to the number of viable dysfunctional segments by all modalities (r = 0.54 to 0.65).Conclusions. In myocardial hibernation, methods evaluating rest perfusion (MCE, Tl-201) or any contractile reserve have a similar high sensitivity but a low specificity for predicting recovery of function. A limited contractile reserve (biphasic response) increases the specificity of DE. Importantly, the three techniques identified all patients who had significant improvement in global ventricular function.(J Am Coll Cardiol 1997;29:985–93)© 1997 by the American College of Cardiology

Background The purposes of this study were to evaluate the comparative accuracy of dobutamine echocardiography and quantitative rest-redistribution 201 Tl tomography in the prediction of recovery of function after revascularization and to assess the relation of contractile reserve to thallium uptake. Methods and Results Thirty-four patients with stable coronary disease and regional dysfunction underwent dobutamine echocardiography (2.5 up to 40 μg·kg −1 ·min −1 ) and rest-redistribution 201 Tl tomography 1 day before revascularization. Resting echocardiography and scintigraphy were repeated at ≥6 weeks. Before revascularization, resting 201 Tl uptake was similar in segments demonstrating biphasic or sustained improvement and was higher than in those exhibiting no change or worsening function during dobutamine. After revascularization, 201 Tl uptake increased only in segments that showed a biphasic response (from 66±12% to 78±13%; P Conclusions In patients with myocardial hibernation, biphasic response during dobutamine is less sensitive but more specific for recovery of function, whereas indexes of 201 Tl scintigraphy are in general more sensitive and less specific, the least accurate being a qualitative assessment of thallium uptake. The sensitivity and specificity of both methods, however, can be altered depending on the quantitative criteria of thallium uptake or combination of responses of the myocardium to dobutamine.

implantation of a BVS, an emerging effective treatment for de-novo coronary artery disease [3] allowed for satisfactory treatment of both the ISR and the in-segment disease. Figure legend: Optical coherence tomography (OCT) appearance pre-implantation of a bioresorbable vascular scaffold (BVS) with significant neointimal proliferation over two layers of stent struts following pre-dilatation to facilitate adequate contrast flow for OCT (Panel A) with significant atheroma also seen at the proximal nonstented segment (Panel B) with balloon related dissection also present. Absorb 3.5 × 18 mm BVS with adequate BVS expansion and apposition over the two previously placed layers of metallic stent struts (Panels C, D and zoomed up image Panel E). Baseline angiographic image before any balloon dilatation (Panel F) shows severe in-stent and significant in-segment stenosis. Final angiographic appearance post BVS was satisfactory (Panel G).

A 62-year–old man presented with progressive exertional dyspnea and angina. His past medical history is notable for coronary artery disease, for which he underwent a coronary artery bypass graft surgery 8 years earlier. A few years afterward, he underwent aortic valve (AV) bypass (AVB) surgery for severe aortic stenosis (AS) using an apicoaortic conduit to the descending aorta consisting of a 16-mm connector and an 18-mm valved conduit (Hancock valve; Medtronic, Minneapolis, MN; Figures 1 and 2; online-only Data Supplement Movie I). After a period of initial improvement in symptoms, the patient developed progressive dyspnea and angina and was referred for additional cardiac workup. Figure 1. An ECG-gated thin-slice contrast-enhanced cardiac computed tomography scan showing a heavily calcified native aortic valve (AV), hypertrophied left ventricle (LV), and the apical LV insertion site of the apicoaortic valved conduit. Figure 2. A 3-dimensional cardiac computed tomography reconstruction image showing the apicoaortic valved conduit, extending from its apical insertion site into the left ventricle (LV) to its insertion site into the descending aorta. Arrow , Conduit valve. The patient underwent a bicycle ergometer test, which showed a diminished functional capacity and was stopped because of fatigue and a hypotensive response. He underwent a 2-dimensional transthoracic echocardiogram with gradual dobutamine infusion. He was found to have a heavily calcified AV (online-only Data Supplement Movie II) with a rest mean transvalvular gradient of 34 mm Hg and velocity of 3.5 m/s, which increased to 50 mm Hg and 4.8 m/s, respectively, at peak dobutamine dose (Figure 3). This corresponded with a …

A large mitral paravalvular leak in a 63-year-old patient was closed by percutaneous placement of 2 Amplatzer Septal Occluder (AGA Medical Corporation, Plymouth, MN) devices. The patient had a residual paravalvular leak and subsequently developed infective endocarditis that was successfully treated by removal of all hardware and implantation of a new valve. Transcatheter treatment of paravalvular leaks may be useful in select patients who are poor candidates for open surgery; however, one must be aware of the potential complications. This report underscores the risk of device infection that may be increased if there is turbulence related to residual paravalvular leaks.

Background The US Food and Drug Administration recently approved a transcatheter aortic valve for patients for whom open heart surgery is prohibitively risky. Methods A multidisciplinary heart valve team partnered with administration to launch a transcatheter aortic valve replacement (TAVR) program. Clinical registries were used to show robust valve caseloads and outcomes at our Veterans Affairs (VA) facility and to project future volumes. A TAVR business plan was approved by the VA leadership as part of a multiphase project to upgrade and expand our surgical facilities. Results The heart valve team completed a training program that included simulations and visits to established TAVR centers. Patients were evaluated and screened through a streamlined process, and the program was initiated successfully. Conclusions Establishing a TAVR program at a VA facility requires a multidisciplinary team with experience in heart valve and endovascular therapies and a supportive administration willing to invest in a sophisticated infrastructure.

Digoxin has been shown to reduce heart failure (HF) hospitalizations with no overall effect on mortality in HF patients. We used cluster analysis to delineate the clinical characteristics of HF patients in whom digoxin therapy was associated with improved or worsened clinical outcomes.The Digitalis Investigation Group (DIG) database was partitioned into 20 clusters. Multivariate Cox regression analyses was used, to identify clusters in which digoxin was associated with either an increase (Mortality(dig)HR1), decrease (Mortality(dig)HR1), or no association with all cause mortality (Mortality(dig)HR-NS); and separately, with an increase (HFA(dig)HR1), decrease (HFA(dig)HR1), or no association (HFA(dig)HR-NS) with HF admissions (HFA).We identified 938 patients in the Mortality(dig)HR1 group, 6818 patients in the Mortality(dig)HR-NS group, and none in Mortality(dig)HR1 group. The Mortality(dig)HR1 group had a higher prevalence of females, diabetes mellitus, hypertension, higher age, systolic blood pressure (SBP), heart rate and ejection fraction (EF), compared to the Mortality(dig)HR-NS group. Similarly, 6325 patients clustered in the HFA(dig)HR1 group, 1431 patients in the HFA(dig)HR-NS group, and none in the HFA(dig)HR1 group. The HFA(dig)HR-NS group had a higher prevalence of females and hypertension, higher SBP, body mass index and EF; and lower prevalence of peripheral edema and third heart sound, compared with the HFA(dig)HR1 group.Thus, the baseline characteristics of patients who did not have reduction in HF hospitalization or who had increased mortality were very similar and included females with hypertension, higher EF and higher SBP. Thus, use of digoxin in patients with this profile may need to be avoided.

Importance The US Food and Drug Administration recently approved the use of a transcatheter aortic valve in patients for whom traditional valve replacement surgery poses a high or prohibitive risk. Our hospital was one of the first Veterans Affairs facilities to launch a transcatheter aortic valve replacement (TAVR) program. Objective To evaluate our early experience with transfemoral TAVR. Design and Setting We retrospectively reviewed the records of all patients who underwent TAVR during the first year of our program at the Department of Cardiothoracic Surgery, Michael E. DeBakey Veterans Affairs Medical Center. Participants The mean (SD) age of the patients was 77 (9) years, and their mean (SD) Society of Thoracic Surgeons predicted risk of mortality score was 8.8 (10.7). Interventions All patients underwent TAVR with the SAPIEN transcutaneous valve. Main Outcome Measures We evaluated operative mortality and major operative morbidity (stroke, myocardial infarction, renal failure necessitating dialysis, and requirement for mechanical circulatory support, as well as vascular complications and requirement for permanent pacemaker), in addition to length of hospital stay and discharge status. Results Between December 21, 2011, and December 13, 2012, a total of 19 transfemoral TAVR procedures were performed at our center. Implantation was successful in all cases. There were no reports of operative (30-day) mortality, prosthetic valve endocarditis, renal failure necessitating dialysis, perioperative myocardial infarction or stroke, or conversion to surgical aortic valve replacement. Seven patients (37%) had mild paravalvular leak, 3 patients (16%) had moderate paravalvular leak, 2 patients (11%) had groin wound complications, 2 patients (11%) required a permanent pacemaker, 1 patient (5%) had a vascular access complication requiring endovascular repair, and 1 patient (5%) required temporary circulatory support (with extracorporeal membrane oxygenation). The mean (SD) length of hospital stay after TAVR was 8.0 (5.9) days. All patients were discharged home. Conclusions and Relevance Transcatheter aortic valve replacement can be performed safely and with good outcomes at a Veterans Affairs facility with a committed multidisciplinary team and substantial experience in heart valve and endovascular therapies.

Infective endocarditis, especially when it involves prosthetic valves, is a serious, often fatal illness. Although antibiotics are essential in management, surgery is required in many patients who develop even incipient heart failure and structural complications. Early identification and referral results in improved mortality and morbidity rates, and there is evidence that surgery should play a larger role in managing infective endocarditis. Patients with intracardiac pacemakers and cardioverting devices represent a growing reservoir of patients with the potential to develop endocarditis.

Objective Our objective was to evaluate the natural history of moderate aortic stenosis in veterans—a unique patient population with significant comorbidities. Methods We retrospectively reviewed the records of all patients who underwent echocardiography at a single veterans affairs hospital during 2006. We identified consecutive patients who had moderate aortic stenosis as indicated by a mean transaortic gradient of 25 to 40 mm Hg, peak aortic jet velocity of 3 to 4 m/s, or aortic valve area of 1.0 to 1.5 cm 2 . The primary end point was defined as survival without aortic valve replacement. Results Of the 104 patients (mean age, 74 ± 10 years), 49% had diabetes, 21% had peripheral vascular disease, 21% were current smokers, 18% had chronic obstructive pulmonary disease, 60% had coronary artery disease, 89% had hypertension, and 31% had a body mass index of 30 kg/m 2 or more. Mean ejection fraction was 49% ± 12%. During the mean follow-up period of 22 months (range, 1-67 months), 30% of patients underwent aortic valve replacement—26% for symptomatic severe aortic stenosis and 4% concomitantly with coronary artery bypass grafting as the primary indicated operation—and 61% died. Event-free survivals were 48%, 24%, and 15% at 1, 3, and 5 years, respectively. Conclusions Our cohort of military veteran patients had significant comorbidities. Event-free survival for such patients who have moderate aortic stenosis is significantly lower than previously reported data suggest. Within this unique group of patients, identifying factors that accelerate the progression of moderate aortic stenosis would help surgeons select patients who may benefit from early aortic valve replacement for moderate aortic stenosis.

We studied the effect of left ventricular (LV) asynchrony and alterations in beta-adrenergic tone on the systolic load (pressure) dependency of LV isovolumic relaxation rate in anesthetized dogs. The time constant (T) of isovolumic exponential pressure decline was used as an index of relaxation rate. Variably afterloaded LV contractions resulted in a progressive increase in LV end-systolic pressure from 124 +/- 6 in the control beat to 176 +/- 11 mmHg in the third beat and a progressive lengthening of T from 19 +/- 2 to 30 +/- 4 ms. The direct relation between LV end-systolic pressure and T was nearly linear (r = 0.98), and the slope (k) of this relation was taken to reflect the systolic load dependency of T. Administration of isoproterenol (n = 6) produced a decrease in k from 0.11 +/- 0.02 to 0.08 +/- 0.02 (P less than 0.05); with propranolol (n = 6), k increased from 0.08 +/- 0.02 to 0.27 +/- 0.04 (P less than 0.01). Right ventricular epicardial pacing (n = 6) produced an asynchronous LV contraction and an increase in k from 0.09 +/- 0.02 (atrial pacing) to 0.25 +/- 0.04 (P less than 0.01). These studies confirm the dependency of LV relaxation rate on systolic loads and indicate that this form of load-dependent relaxation can be modified by alterations in beta-adrenergic tone and LV asynchrony. The observed alterations suggest the importance of temporal dispersion of the contraction-relaxation sequence as a mechanism responsible for disturbed relaxation.

Reoxygenation of hypoxic isolated cardiac muscle results in prolonged duration of contraction-relaxation. To determine whether similar mechanical changes occur in the intact left ventricle (LV), and especially to assess the influence of prolonged relaxation on LV diastolic stiffness, we examined LV pressure transients (micromanometer) and changes in myocardial segment length (ultrasonic transit time) during reoxygenation in 22 anesthetized dogs following 15 minutes of hypoxia (PaO2 = 21 +/- 2 mm Hg). The time constant (T) of LV isovolumic exponential pressure decline was used as an index of myocardial relaxation; LV end-diastolic stiffness was assessed from stiffness constants derived from multiple coordinates of end-diastolic pressure and segment length (volume loading). During reoxygenation, after LV systolic pressure and segment length measurements had returned to control levels, relaxation was prolonged; T increased from a control of 32 +/- 2 to 44 +/- 3 msec at 5 minutes of reoxygenation (P less than 0.01). Prolonged relaxation resulted in a consistent increase in LV early-diastolic pressures. Furthermore, calculated values for LV end-diastolic stiffness increased during reoxygenation when the next beat began less than 3.5 T after maximum negative dP/dt; this condition was present more frequently at a heart rate of 150 beats/min than at 120 beats/min. Thus, rapid correction of acute hypoxia in the dog results in prolonged LV relaxation; prolonged relaxation can influence LV end-diastolic stiffness when relaxation is sufficiently slow and/or when diastole is sufficiently short.

To determine the mechanisms of pulsus paradoxus during asthma, six subjects known to have cold air bronchial hyperreactivity were studied while in a quiescent phase of their disease. All were free of significant airway obstruction at the time of study. After placement of an esophageal balloon to estimate intrathoracic pressure, the subjects were assessed during quiet breathing, resistive airway loading and then during a stable period of airway obstruction induced by cold air. Steady state left ventricular volume and performance were measured using radionuclide ventriculography; right ventricular volume was calculated from the stroke volume ratio and right ventricular ejection fraction. Cardiac cycles were segregated according to their occurrence in inspiration or expiration using a flow signal from a pneumotachograph. Combined inspiratory and expiratory resistance produced pulsus paradoxus and changes in esophageal pressure that were similar to those during asthma and significantly greater than those during quiet breathing. These changes were accompanied by decreases in left ventricular diastolic volume and stroke volume during inspiration, and increases in these variables during expiration; right ventricular volume and stroke volume demonstrated changes reciprocal to those seen in the left ventricle. These data indicate that during periods of increase in airway resistance, abnormal pulsus paradoxus results from an exaggeration in the normal inspiratory-expiratory difference in stroke volume mediated primarily by the effects of intrathoracic pressure on ventricular preload.

Ten normal subjects performed the Valsalva maneuver before and after the administration of propranolol (1 mg/kg). Changes in left ventricular (LV) size and function were assessed with noninvasive techniques (echocardiography and sphygmomanometer). Data were obtained at baseline, at 20 seconds of the strain phase (phase II) and 10 seconds after the release of strain (phase IV). In the control state (before propranolol), blood pressure decreased during phase II and exceeded baseline after the release of strain (“overshoot”) in phase IV; after the administration of propranolol, the pressure overshoot characteristic of phase IV was no longer present. End-diastolic dimension decreased during the strain phase, but returned to baseline values during recovery in both control and propranolol states. LV stress-dimension and stress-shortening relations before and after propranolol indicate that an increase in LV contractility beginning during phase II and extending into phase IV was attenuated after propranolol. Although the absence of phase IV blood pressure overshoot may be clinically useful in identifying patients with impaired left ventricular function, β-adrenergic receptor blocking agents can also produce this hemodynamic response in the presence of normal ventricular function.

Observations that the inner (subendocardial) half of the left ventricular wall contributes more to total left ventricular wall thickening than the outer (subepicardial) half may have important implications in the analysis of myocardial fiber length transients. Accordingly, we measured endocardial and midwall shortening and lengthening rates in normal and hypertrophic heart and compared the results obtained with conventional methods of measurement with those obtained with a modified model that does not depend on use of conventional assumptions about the midwall. This modified (two-shell) cylindrical model) method considers the substantial contribution of inner wall thickening and thus does not require the assumption of a theoretical midwall fiber that remains at the midwall throughout the cardiac cycle. Echocardiographic data from six normal subjects and six patients with concentric left ventricular hypertrophy (LVH) were examined; left ventricular wall thickness ranged from 8 to 10 mm in normal subjects and from 11 to 16 mm in the patients with LVH. By design, the standard measurements of left ventricular size (diastolic and systolic dimensions) and systolic function (fractional shortening and endocardial fiber shortening velocities) were equal in the two groups. Endocardial, conventional midwall, and modified midwall methods all indicate reduced fiber lengthening rates in patients with LVH; peak fiber lengthening rates for normal and LVH groups were 4.5 +/- 0.7 vs 3.1 +/- 0.8 sec-1 (p less than .02) at the endocardium, 2.3 +/- 0.4 vs 1.6 +/- 0.4 sec-1 (p less than .02) at the midwall (conventional method), and 2.1 +/- 0.3 vs 1.4 +/- 0.3 sec-1 (p less than .01) at the midwall (modified method).(ABSTRACT TRUNCATED AT 250 WORDS)

Serial changes in left ventricular (LV) size and function during the adaptation to chronic pressure overload and the transition to pump failure were studied in 16 conscious dogs (aortic bands placed at 8 weeks of age). Echocardiographic data at baseline and at 3, 6, 9, and 12 months after banding revealed a progressive increase in LV mass in all dogs. In six dogs with LV pump failure, there was a progressive decline in circumferential fiber shortening (29 +/- 4% at 12 months); this was significantly less than that seen in five littermate controls (38 +/- 3%, p less than 0.05). The average LV to body weight ratio in this group was 9.8 +/- 2.7 g/kg. In 10 dogs without pump failure (compensated LVH group), shortening exceeded that seen in the controls (43 +/- 4%, p less than 0.05); the LV to body weight ratio was 7.7 +/- 1.0 g/kg. At 12 months (cardiac catheterization), the LV end-diastolic pressure was higher in the failure (25 +/- 15 mm Hg) than in the compensated group (8 +/- 5 mm Hg, p less than 0.05); mean systolic stress was also higher in the failure group (313 +/- 67 g/cm2) than in the compensated group (202 +/- 53 g/cm2, p less than 0.05). The transmural distribution of myocardial blood flow was measured (at 12 months) with the radioactive microsphere technique; flow data were then related to an index of demand (a stress-time index). There was preferential blood flow to the subendocardial layers in the control (endo/epi = 1.28) and compensated hearts (endo/epi = 1.10), but in the failure group there was a relative decrease in subendocardial flow (endo/epi = 0.92). However, the absolute values for subendocardial flow in the normal, compensated, and failure groups were 77 +/- 54, 125 +/- 48, and 113 +/- 64 ml/min/100 g; the stress-time indexes in the subendocardial shell were 38 +/- 11, 74 +/- 19, and 93 +/- 34 g sec.10(2)/cm2/min. Despite what appears to be a marginal balance between blood flow and the stress time index in the failure group, the myocardial high energy phosphates were not depleted and the inoptropic state was not depressed. In this model of LV hypertrophy, the observed differences in fiber shortening can be explained on the basis of the inverse afterload-shortening relation; pump failure was due to an inadequate LV hypertrophy with afterload excess.(ABSTRACT TRUNCATED AT 400 WORDS)

Isolated, isovolumic rat hearts, perfused by Krebs-Henseleit buffer at constant coronary flow rate, were used to explore the hypothesis that endogenous cardiac glutathione provides protection against myocardial dysfunction associated with short periods of ischemia. Experimental animals were depleted of cardiac glutathione to 35% of control levels by intraperitoneal injections of diethylmaleate (DEM). Left ventricular pressure, coronary perfusion pressure, and glutathione levels were measured in control and experimental hearts after 60 minutes of oxygenated perfusion and after 20 minutes of global, no-flow ischemia and 30 minutes of reperfusion. With each protocol, both control and glutathione-depleted hearts received either standard buffer or one supplemented with 2 mM glutathione. Recovery of systolic function after ischemia-reperfusion was impaired in DEM-treated hearts compared with controls. In addition, the rise in perfusion pressure and chamber stiffness was also greater in DEM-treated hearts compared with controls. Recovery in glutathione-depleted hearts was improved when the reperfusate was supplemented with glutathione. In addition, the supplemented reperfusate prevented the decrease in compliance and the increase in coronary perfusion pressure in the glutathione-depleted hearts. Ischemia-reperfusion alone were not associated with a significant alteration in myocardial glutathione levels. Prewashout myocardial levels of glutathione were elevated after reperfusion with glutathione-supplemented buffer but fell to baseline levels after a short washout period. These studies demonstrate that endogenous glutathione is important in protection of myocardium from injury after ischemia-reperfusion, presumably by modifying levels of active oxygen intermediates. The smaller changes in left ventricular pressure and coronary resistance after administration of GSH probably reflects an extracellular mechanism because benefit is seen soon after reperfusion.

Oxygen-derived free radicals (OFR) have been implicated as mediators of tissue injury in various disease states. Their participation in myocardial injury due to ischemia-reperfusion has also been suggested. To characterize the mechanical dysfunction associated with OFR-induced injury, we studied alterations in isometric contractions of rat papillary muscle at 28 degrees C. A purine-xanthine oxidase system was used to generate OFR. Neither purine nor xanthine oxidase alone had significant effects on rest or active tension, duration of the contraction, or peak rates of tension development or decline. In contrast, their combination resulted in a reduction of active tension to 38% of base-line values without alteration in rest tension. This reduction was largely due to a decline in the peak rate of tension development. When catalase or superoxide dismutase was introduced into the bath prior to the generation of OFR, catalase but not superoxide dismutase offered essentially complete functional protection. These results substantiate that impaired myocardial function can result from exposure to OFR. In this case the active radicals appear to be either peroxides or hydroxyl and not superoxide. These observations provide a basis for understanding the functional protection afforded ischemic myocardium by OFR scavenging enzymes.

Objectives. The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial was designed to compare outcomes of patients with a non–Q wave myocardial infarction (NQMI) who were randomized prospectively to an early “invasive” strategy versus an early “conservative” strategy. The primary objective was to compare early and late outcomes between the two strategies using a combined trial end point (all-cause mortality or nonfatal infarction) during at least 1 year of follow-up. Background. Because of the widely held view that survivors of NQMI are at high risk for subsequent cardiac events, management of these patients has become more aggressive during the last decade. There is a paucity of data from controlled trials to support such an approach, however. Methods. Appropriate patients with a new NQMI were randomized to an early “invasive” strategy (routine coronary angiography followed by myocardial revascularization, if feasible) versus an early “conservative” strategy (noninvasive, predischarge stress testing with planar thallium scintigraphy and radionuclide ventriculography), where the use of coronary angiography and myocardial revascularization was guided by the development of ischemia (clinical course or results of noninvasive tests, or both). Results. A total of 920 patients were randomized (mean follow-up 23 months, range 12 to 44). The mean patient age was 61 ± 10 years; 97% were male; 38% had ST segment depression at study entry; 30% had an anterior NQMI; 54% were hypertensive; 26% had diabetes requiring insulin; 43% were current smokers; 43% had a previous acute myocardial infarction; and 45% had antecedent angina within 3 weeks of the index NQMI. Conclusions. Baseline characteristics were compatible with a moderate to high risk group of patients with an NQMI.

Segmental early relaxation, a form of left ventricular asynchrony, refers to lengthening of a myocardial segment before mitral valve opening. This phenomenon may occur in normal and diseased hearts; when it is seen in a diseased ventricle it may occur in either the abnormally contracting segment or the normal segment. Experimental data indicate that altered loading conditions, especially nonuniform distribution of load or functional inhomogeneities (as may occur with regional ischemia), or both, may result in asynchronous relaxation of the left ventricle.

Postextrasystolic (PES) relaxation of the left ventricle was studied in 24 anesthetized dogs using the time constant (tau) of the left ventricular isovolumic pressure decline as an index of global relaxation velocity. Using programmed atrial stimulation and a control RR interval of 500 msec, the "coupling interval/compensatory pause" was varied from 400/600 msec to 250/750 msec, and left ventricular pressure-segment length data from control beats were compared with data from PES beats. Contractile state and fractional shortening increased in the PES beat, but the relaxation time constant remained unchanged (control, 35 +/- 3 msec; PES at 250/750 msec, 36 +/- 3 msec) (p = NS). Pretreatment with propranolol did not qualitatively influence these results. Isoproterenol and calcium were given in doses sufficient to increase the time derivative of isovolumic pressure (maximal positive dP/dt) by an amount equal to that obtained with PES potentiation (approximately 50%); isoproterenol produced a substantial decrease in the relaxation time constant (38 +/- 4 to 30 +/- 6 msec, p less than 0.01), whereas calcium administration produced only a small decrease in the time constant (30 +/- 5 to 27 +/- 5 msec, p less than 0.05). Thus, in the intact dog heart, some positive inotropic interventions augment contraction and speed relaxation, but PES potentiation of contraction is not associated with a change in relaxation velocity.

We studied the effect of an isolated increase in preload on isovolumetric relaxation in the intact dog heart and isometric relaxation in isolated cardiac muscle (dog and rat) preparations. In eight anesthetized dogs, 8 to 12 ml of blood was infused into the left ventricle during a single diastole. The exponential time constant (T) of isovolumetric relaxation was measured in single-beat experiments in which the left ventricular systolic pressure increased (112 +/- 2 to 128 +/- 3 mm Hg; p less than .05, n = 62). In a second series of experiments, left ventricular systolic pressure was held constant (109 +/- 2 to 107 +/- 2 mm Hg; p = NS, n = 23) by simultaneous ventricular infusion and aortic unloading. In the first protocol, T increased from 28.0 +/- 0.4 to 30.7 +/- 0.4 msec (p less than .05), whereas in the second protocol (constant systolic pressure) there was no change in T. The time course of isometric relaxation was also studied in six rat left ventricular papillary muscles and four dog right ventricular trabecular muscles. Preload was varied from 30% to 100% of the peak of the isometric length-tension curve in each muscle. Over this wide range of preload, the isometric force decline recordings were superimposable as long as the comparisons were made at equal levels of total load. Thus an isolated increase in preload does not influence the time course of isovolumetric relaxation.

To separate the effects of hemodialysis on loading conditions from those on contractile state, six patients with concentric left ventricular hypertrophy and normal left ventricular function were studied before, during, and after hemodialysis. Two-dimensional-directed M-mode ultrasound was used to measure left ventricular dimensions and wall thickness; a sphygmomanometer and carotid pulse recording were used to determine peak and end-systolic blood pressure. From these data, meridional stress at end systole was calculated and stress-dimension and stress-shortening relations were derived; measurements of metabolic parameters were made simultaneously. Heart rate and systolic blood pressure were stable throughout dialysis. Reductions in left ventricular dimensions and increased shortening were evident by 30 minutes of dialysis and were largely complete by mid-dialysis. These changes coincided with a decrease in potassium and an increase in ionized calcium but not in pH, which changed only in the latter half of dialysis. When stress-dimension and stress-shortening relations were examined, both individual and group data for all coordinates before, during, and after dialysis demonstrated an excellent linear fit consistent with a single contractile state. We conclude that in stable patients with left ventricular hypertrophy, the reduction in heart size and improvement in shortening are due primarily to reductions in preload and afterload.

Right ventricular pacing alters left ventricular synchrony and loading conditions, each of which may independently influence left ventricular relaxation. Addition of a properly timed atrial contraction by using sequential atrioventricular (AV) pacing minimizes changes in left ventricular loading conditions, but ventricular asynchrony persists. To separate the effects of altered loading from those of asynchrony, the effects of right ventricular pacing and sequential AV pacing on the rate of isovolumic pressure decline (relaxation time constant), myocardial (segment) lengthening rate and chamber (minor axis dimension) filling rate were examined. In 12 open chest anesthetized dogs, left ventricular pressure (micromanometer) and either left ventricular free wall segment length transients (n = 6) or minor axis dimension transients (n = 6) were measured during right atrial, right ventricular and sequential AV pacing; length and dimension were measured using ultrasonic crystals.Compared with right atrial pacing, right ventricular pacing produced a decrease in systolic pressure, a reduction in fractional shortening, a prolongation of the relaxation time constant (23.5 ± 0.7 to 29.8 ± 0.8 ms, p < 0.05), slower peak segment lengthening rate (6.2 ± 0.6 to 4.6 ± 0.8 s−1, p < 0.05) and a slower rate of increase in chamber dimension (3.5 ± 0.1 to 2.7 ± 0.1 s p < 0.05). In contrast, systolic pressure and fractional shortening did not change during sequential AV pacing; however, the relaxation time constant remained prolonged (23.5 ± 0.7 to 30.0 ± 0.8 ms, p < 0.05) and peak lengthening and filling rates (5.9 ± 0.6 versus 5.3 ± 0.8, p < 0.05 and 3.5 ± 0.1 versus 3.0 ± 0.1 s−1, p < 0.05, respectively) showed small but statistically significant declines.Thus, pacing-induced left ventricular asynchrony caused a decrease in the global and regional indexes of left ventricular relaxation rate that is not closely related to left ventricular loading conditions or shortening.

The introduction of transcatheter aortic valve replacement (TAVR) has renewed interest in balloon aortic valvuloplasty (BAV) for severe aortic stenosis (AS). It is unclear whether technical advances and increased experience associated with TAVR development have resulted in improved BAV outcomes. We