William G. Kussmaul

Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure.

BackgroundOptimal timing of cardiac transplantation in ambulatory patients with severe left ventricular dysfunction is often difficult. To determine whether measurement of peak oxygen consumption (Vo2) during maximal exercise testing can be used to identify patients in whom transplantation can be safely deferred, we prospectively performed exercise testing on all ambulatory patients referred for transplant between October 1986 and December 1989. Methods and ResultsPatients were assigned into one of three groups on the basis of exercise data: Group 1 (n =35) comprised patients accepted for transplant (Vo2<14 ml/kg/min); group 2 (n =52) comprised patients considered too well for transplant (Vo2 >14 ml/kg/min); and group 3 (n =27) comprised patients with low Vo2 rejected for transplant due to noncardiac problems. All three groups were comparable in New York Heart Association functional class, ejection fraction, and cardiac index (p=NS). Pulmonary capillary wedge pressure was significantly lower in group 2 than in either group 1 or 3 (p<0.05), although there was wide overlap. Patients with preserved exercise capacity (group 2) had cumulative 1- and 2-year survival rates of 94% and 84%, which are equal to survival levels after transplantation. In contrast, patients rejected for transplant (group 3) had survival rates of only 47% at 1 year and 32% at 2 years, whereas patients awaiting transplantation (group 1) had a survival rate of 790% at 1 year (both (p <0.005 versus patients with Vo2 > 14 ml/kg/min). All deaths in group 2 were sudden. By univariate and multivariate analyses, peak Vo2 was the best predictor of survival, with only pulmonary capillary wedge pressure providing additional prognostic information. Conclusions.These data suggest that cardiac transplantation can be safely deferred in ambulatory patients with severe left ventricular dysfunction and peak exercise Vo2 of more than 14 ml/min/kg. (Circulation 1991;83:778–786)

Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features.

The clinical, electrocardiographic, and coronary hemodynamic responses to sequential 90-second occlusions of the left anterior descending coronary artery in 12 patients undergoing elective percutaneous transluminal coronary angioplasty were examined. Transmyocardial lactate metabolism was examined in an additional group of seven patients with clinical and hemodynamic features similar to the first group. We noted that in comparison with the initial balloon occlusion the second occlusion was characterized by less subjective anginal discomfort, less ST segment shift (0.44 +/- 0.13 versus 0.21 +/- 0.07 mV, p = 0.01), and lower mean pulmonary artery pressure (25 +/- 1.0 versus 20 +/- 1.7 mm Hg, p = 0.005). In addition, for the same heart rate-blood pressure product, cardiac vein flow during the second inflation was significantly lower than that recorded during the first inflation (96 +/- 1.4 versus 83 +/- 2.4 ml/min, p = 0.005). Finally, there was significantly less myocardial lactate production during the second inflation (lactate extraction ratio: first inflation, -0.11 +/- 0.03; second inflation, -0.03 +/- 0.02; p = 0.04). We conclude that the lessened clinical, electrocardiographic, hemodynamic, and metabolic evidence of myocardial ischemia during the second of two periods of coronary artery occlusion during percutaneous transluminal coronary angioplasty supports the concept of adaptation to myocardial ischemia (ischemic preconditioning).

Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty.

To test the hypothesis that pretreatment with adequate antiplatelet therapy reduces the likelihood of acute coronary thrombosis during routine percutaneous transluminal coronary angioplasty (PTCA), we reviewed, blinded to treatment group, the films and records of 300 consecutive initially successful PTCAs. Films before PTCA, immediately after, and at least 30 min after the last balloon inflation were assessed for the presence of any thrombus at the PTCA site. We excluded 37 patients who received streptokinase before PTCA or who had 100% occlusion or thrombus on pre-PTCA films. New thrombi were classified as clinically significant (defined as causing 100% occlusion or requiring emergency surgery or streptokinase therapy) or as not significant (not causing an acute problem or requiring intervention). Patients were classified into three groups, based on the type and extent of antiplatelet therapy received. Group 1 (no aspirin, n = 121) consisted of patients who did not receive aspirin either before admission or in hospital before PTCA (with or without dipyridamole). Group 2 (standard treatment, n = 110) received aspirin with or without dipyridamole but did not receive both drugs before admission and in hospital before PTCA. Group 3 (maximal treatment, n = 32) received both aspirin and dipyridamole before admission and in hospital before PTCA. New thrombi were detected at 39 (14.8%) PTCA sites, of which 15 (5.7% of all PTCA sites) were considered clinically significant. Group 1 had the highest incidence of both thrombus (21.5%) and clinically significant thrombus (10.7%). A reduction was seen in group 2 in thrombus (11.8%; p = .07) and in clinically significant thrombus (1.8%; p = .005). Group 3 had no thrombus (p = .001) and no clinically significant thrombus (p = .04). In addition to inadequate pretreatment with antiplatelet therapy, univariate analyses demonstrated several other risk factors for thrombus: higher percent diameter stenosis before PTCA (p less than .008), higher platelet count (p = .013), and current smoking (p = .03). Only higher platelet count (p less than .001) and inadequate pretreatment (p = .001) were associated with clinically significant thrombus. Stepwise logistic regression analysis demonstrated that for thrombus, the lack of effective antiplatelet therapy was the most discriminatory variable, followed by current smoking, higher percent diameter stenosis, and dissection. For clinically significant thrombus, once the lack of pretreatment with effective antiplatelet therapy was considered, no other factors added significant discriminatory information.(ABSTRACT TRUNCATED AT 400 WORDS)

Pulmonary artery hemodynamics in primary pulmonary hypertension

OBJECTIVES The present investigation compared and contrasted steady and pulsatile pulmonary hemodynamics at rest and during exercise in patients with primary pulmonary hypertension and normal control subjects. BACKGROUND A complete description of the relation between pressure and flow in the pulmonary circulation includes both steady and pulsatile hemodynamic behavior. Patients with primary pulmonary hypertension provide a unique opportunity to study the effects of primary alterations in pulmonary vasculature on pulmonary artery vascular hydraulic load. METHODS Catheter tip pressure and velocity recordings from the main pulmonary artery in 8 patients with primary pulmonary hypertension and 10 control subjects were used to derive the pulmonary artery input impedance spectrum and the extent of pulse wave reflection at rest and during exercise. RESULTS As expected, in patients with primary pulmonary hypertension, mean pulmonary artery pressure (50 +/- 10 mm Hg) and pulmonary vascular resistance (880 +/- 446 dynes.s.cm-5) were markedly elevated at rest and remained so during exercise (mean pressure 71 +/- 15 mm Hg, mean resistance 750 +/- 530 dynes.s.cm-5). Pulmonary artery characteristic impedance was elevated at rest and did not change with exercise (rest 55 +/- 25 dynes.s.cm-5; exercise 66 +/- 33 dynes.s.cm-5). Measures of arterial wave reflection indicated that the extent of wave reflection in the pulmonary bed in those with primary pulmonary hypertension is large at rest (reflection coefficient 0.89 +/- 0.09) and that the composite reflected wave arrived during the midportion of right ventricular ejection. Although the extent of wave reflection decreased with exercise (reflection coefficient 0.81 +/- 0.10, p < 0.05), the magnitude and timing of these reflections remained adverse. Furthermore, in patients with primary pulmonary hypertension, the stroke volume response to exercise was strongly related to rest levels of pulmonary artery diastolic pressure, pulmonary vascular resistance and the reflection factor, whereas no such relation was found in the control subjects. CONCLUSIONS In addition to the expected abnormalities in steady measures of pulmonary artery hemodynamics at rest in patients with primary pulmonary hypertension, rest and exercise measures of oscillatory behavior (characteristic impedance and pulse wave reflection) are perturbed. Measures of steady and pulsatile behavior, particularly wave reflection, appear to have an important role in the exercise response of these patients.

Constrictive pericarditis versus restrictive cardiomyopathy: a reappraisal and update of diagnostic criteria.

Distinguishing constrictive pericarditis from restrictive cardiomyopathy is a difficult clinical challenge. We review published reports in which hemodynamic criteria were used to differentiate these two diagnoses. There were 82 cases of constriction and 37 cases of restriction. The overall predictive accuracy of the difference between right and left ventricular end-diastolic pressures (RVEDP and LVEDP), RV systolic pressure, and the ratio of RVEDP to RV systolic pressure were 85%, 70%, and 76%, respectively. If all three criteria were concordant, the probability of having correctly classified the patient was greater than 90%. However, one fourth of patients could not be classified by hemodynamic criteria. There are few data to support the use of hemodynamic measurements after exercise or volume infusion to separate these two groups. Numerous recent studies have reported on the ability of left ventriculography, Doppler echocardiography, or radionuclide angiography to distinguish constriction from restriction. Many of the proposed indices appear promising, but these studies suffer from small sample size, potential selection bias, and complexity of the proposed criteria, which have limited their widespread application. New imaging technologies, such as CT scanning or MRI have been applied in a limited number of cases, but appear to be a sensitive means of detecting abnormal pericardium. Endomyocardial biopsy has proven useful in establishing the diagnosis of infiltrative cardiomyopathies, eliminating in those cases the need for surgical intervention. The finding of myocarditis must be considered a nonspecific finding that does not preclude thoracotomy. Since constrictive pericarditis is a surgically curable condition, the distinction between constrictive and restrictive disease is of critical importance. Taking into account the relative contribution of data derived from hemodynamic, imaging,and biopsy studies, we propose an algorithm for the selection of appropriate candidates for pericardial biopsy and stripping.

Characteristics of vascular hydraulic load in patients with heart failure.

Aortic input impedance and hydraulic power were derived from simultaneous catheter recordings of ascending aortic pressure and velocity in eight normal subjects and 11 age-matched subjects with clinical heart failure secondary to idiopathic congestive cardiomyopathy. Resting data revealed the characteristic depression of cardiac output and elevation of systemic vascular resistance in patients with heart failure. The pulsatile component of vascular hydraulic load, characteristic impedance (Zc), was similar in both groups (Zc normal: 85 +/- 30 dyne-sec-cm-5; Zc cardiomyopathy: 93 +/- 33 dyne-sec-cm-5). The oscillatory fraction of aortic input power in patients with heart failure (14 +/- 4%) was also similar to that of normal subjects (11 +/- 2%). The transition from rest to exercise in patients with heart failure was marked by a decrease in the steady component of arterial hydraulic load, although characteristic impedance did not change. A similar qualitative response occurred in normal subjects, although the systemic vascular resistance during exercise remained above normal in patients with heart failure. The modulus of the first harmonic of impedance significantly decreased during exercise in normal subjects but did not change significantly in patients with heart failure. Furthermore, the modulus of the first harmonic of the reflection coefficient decreased significantly during exercise in normal subjects but did not change in patients with heart failure in spite of systemic vasodilation. Exercise appears to impose no additional increase in vascular hydraulic load on the ejecting left ventricle. The similar aortic characteristic impedances in patients with heart failure and in normal subjects, at rest and during exercise, are consistent with a constant oscillatory fraction of input power.

Influence of heparin therapy on percutaneous transluminal coronary angioplasty outcome in patients with coronary arterial thrombus

The clinical and angiographic outcome of 18 patients with coronary thrombus undergoing percutaneous transluminal coronary angioplasty without antecedent heparin therapy was compared to that of a group of 35 patients receiving pre-procedural heparin therapy. The former group had a significant reduction in angiographic success (61 vs 94%, p less than 0.05) and a significant increase in immediate postprocedural thrombotic arterial occlusion (33 vs 6%, p less than 0.05). This difference existed despite equivalent frequencies of antiplatelet therapy. Prolonged intravenous heparin therapy before angioplasty in the setting of coronary thrombus improves the overall success rate and lessens the likelihood of periprocedural coronary arterial thrombosis.

Pressure recovery in aortic valve stenosis.

BACKGROUND Pressure recovery is the variable increase in lateral pressure downstream from a stenotic orifice. The magnitude and clinical significance of pressure recovery in aortic valve stenosis are poorly defined. METHODS AND RESULTS We obtained high-fidelity pressure and velocity recordings in 11 patients with isolated significant aortic valve stenosis at the time of diagnostic cardiac catheterization. Systematic catheter pullback from the left ventricular cavity revealed a consistent although variable subvalvular gradient. Further pullback across and distal to the region of the stenosed aortic valve revealed a consistent and progressive increase in the ascending aortic pressure. This increase in lateral pressure occurred pari passu with a diminution in amplitude of the velocity pulse. The extent of pressure recovery was directly related to systemic blood flow and transvalvular flow but inversely related to the Gorlin-derived aortic valve area. CONCLUSIONS These findings have potentially important implications for the hemodynamic evaluation of mild to moderately severe aortic valve stenosis. The extent of pressure recovery may be of additional utility in the assessment of aortic valve stenosis under varying physiological states.

Right ventricular-pulmonary arterial interactions

The application of pulsatile models to hemodynamic data has made possible a more complete understanding of the relationship of pulmonary pressure and flow. To review the genesis of these concepts, the unique characteristics of the pulmonary artery and right ventricle are outlined as a basis for understanding why differences in their pulsatile properties from the systemic circuit must exist. The pulmonary impedance spectrum is introduced and the concept of optimal right ventricular-pulmonary artery coupling is explored based on a review of extensive experimental data. Finally, available studies of normal pulmonary impedance in man and abnormal impedance in human disease states are reviewed, with emphasis on disturbances in optimal ventricular-vascular coupling. The important implications of these concepts for understanding and treatment of cardiovascular disease are developed.

Intravascular ultrasonographic assessment of the results of coronary artery stenting

We studied 12 patients undergoing elective coronary stent implantation for either recurrent restenosis or adverse lesion appearance. By use of a 4.8F 20 MHz intravascular ultrasound catheter, the conventional angioplasty site was examined before and after coronary stent implantation. Quantitative angiographic analysis revealed the expected excellent final result with a group mean poststent diameter reduction of 14 +/- 9% and a cross-sectional area reduction of 22 +/- 13%. Angiographic analysis also indicated an increase in minimum stenosis diameter from 1.8 +/- 0.6 mm after conventional balloon angioplasty to 2.8 +/- 0.3 mm after coronary stent implantation. Quantitative analysis of the corresponding intravascular ultrasound images, however, revealed significant residual endoluminal obstruction. Fractional plaque area remained unchanged from 30 +/- 12% after conventional balloon angioplasty to 32 +/- 11% after stent implantation. The circumferential distribution of plaque increased significantly from 0.44 +/- 0.17 to 0.55 +/- 0.15 (p = 0.03) after stent implantation. Despite the lack of significant change in the ultrasound-determined minimum stenosis diameter after stent placement, there was a borderline significant increase in the plaque-free lumen area (before stent, 6.35 +/- 1.55 mm2; after stent, 7.25 +/- 1.6 mm2; p = 0.06). Thus, in contrast to the substantial improvement in the angiographically assessed residual luminal obstruction after stent implantation compared with the prestent condition, considerably less improvement was found by intravascular ultrasound-assessed examination. Morphometric analysis indicated a tendency toward circumferential remodeling of plaque. The inherently different approaches to vascular imaging represented by contrast angiography and intravascular ultrasound techniques appear to provide complementary information.(ABSTRACT TRUNCATED AT 250 WORDS)