Paul S. Hees

Independent effects of preload, afterload, and contractility on left ventricular torsion

Shortening of oblique left ventricular (LV) fibers results in torsion. A unique relationship between volume and torsion is therefore expected, and the effects of load and contractility on torsion should be predictable. However, volume-independent behavior of torsion has been observed, and the effects of load on this deformation remain controversial. We used magnetic resonance imaging (MRI) with tagging to study the relationships between load and contractility, and torsion. In ten isolated, blood-perfused canine hearts, ejection was controlled by a servopump: end-diastolic volume (EDV) was controlled by manipulating preload parameters and end-systolic volume (ESV) by manipulating afterload using a three-element windkessel model. MRI was obtained at baseline, two levels of preload alteration, two levels of afterload alteration, and dobutamine infusion. An increase in EDV resulted in an increase in torsion at constant ESV (preload effect), whereas an increase in ESV resulted in a decrease in torsion at constant EDV (afterload effect). Dobutamine infusion increased torsion in association with an increase in LV peak-systolic pressure (PSP), even at identical EDV and ESV. Multiple regression showed correlation of torsion with preload (EDV), afterload (ESV), and contractility (PSP; r = 0.67). Furthermore, there was a close linear relationship between torsion and stroke volume (SV) and ejection fraction (EF) during load alteration, but torsion during dobutamine infusion was greater than expected for the extent of ejection. Preload and afterload influence torsion through their effects on SV and EF, and there is an additional direct inotropic effect on torsion that is independent of changes in volume but rather is force dependent. There is therefore potential for the torsion-volume relation to provide a load-independent measure of contractility that could be measured noninvasively.

Cardiac Rhythm after the Mustard Operation for Complete Transposition of the Great Arteries

The Mustard operation corrects the effects of congenital transposition of the great arteries by creating an intraarterial baffle to direct pulmonary venous blood to the tricuspid orifice and systemic venous blood to the mitral orifice. To identify the long-term effects of this procedure, we followed 372 patients with complete transposition of the great arteries who survived the Mustard operation for at least three months. The mean follow-up period was 4.5 years (range, 0.4 to 15.9); the mean age at operation was 2.0 years. Mean resting heart rates were consistently lower than those for age-matched normal children. Seventy-six per cent of the patients had sinus rhythm during the year of operation--a figure that decreased to 57 per cent by the end of the eighth postoperative year. Twenty-five patients died during the follow-up period, nine suddenly. Life-table analysis revealed a cumulative survival rate of 91 per cent for 11 years and 71 per cent for 15 years after the operation. No strong risk factor for sudden unexpected death identified. This study demonstrates that extended survival among patients with transposition can be expected after the Mustard operation. However, over time there is a decreasing prevalence of normal sinus rhythm in survivors, as well as a small risk of sudden death.

Fitness, fatness and activity as predictors of bone mineral density in older persons

Abstract. Stewart KJ, DeRegis JR, Turner KL, Bacher AC, Sung J, Hees PS, Tayback M, Ouyang P (Johns Hopkins Bayview Medical Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA). Fitness, fatness, and activity as predictors of bone mineral density in older persons. J Intern Med 2002; 252: 381–388.

Effects of afterload on regional left ventricular torsion

OBJECTIVE To determine if left ventricular torsion, as measured by magnetic resonance tissue tagging, is afterload dependent in a canine isolated heart model in which neurohumoral responses are absent, and preload is constant. METHODS In ten isolated, blood perfused, ejecting, canine hearts, three afterloads were studied, while keeping preload constant: low afterload, high afterload (stroke volume reduced by approx. 50% of low afterload), and isovolumic loading (infinite afterload). RESULTS There were significant effects of afterload on both torsion (P < 0.05) and circumferential shortening (P < 0.0005). Between low and high afterloads, at the anterior region of the endocardium only, where torsion was maximal, there was a significant reduction in torsion (15.1 +/- 2.2 degrees to 7.8 +/- 1.8 degrees, P < 0.05). Between high afterload and isovolumic loading there was no significant change in torsion (7.8 +/- 1.8 degrees to 6.2 +/- 1.5 degrees, P = NS). Circumferential shortening at the anterior endocardium was significantly reduced both between low and high afterload (-0.19 +/- 0.02 to -0.11 +/- 0.02, P < 0.0005), and also between high afterload and isovolumic loading (-0.11 +/- 0.02 to 0.00 +/- 0.02, P < 0.05). Plots of strains with respect to end-systolic volume demonstrated a reduction in both torsion and shortening with afterload-induced increases in end-systolic volume. Torsion, but not circumferential shortening, persisted at isovolumic loading. CONCLUSIONS Maximal regional torsion of the left ventricle is afterload dependent. The afterload response of torsion appears related to the effects of afterload on end-systolic volume.

Usefulness of anthropometrics and dual-energy x-ray absorptiometry for estimating abdominal obesity measured by magnetic resonance imaging in older men and women

PURPOSE Increasing evidence suggests that abdominal obesity may be a better predictor of disease risk than total fatness. This study sought to determine how obesity and fat distribution measured by readily available anthropometric and dual-energy x-ray absorptiometry (DXA) methods is related to abdominal obesity assessed by magnetic resonance imaging (MRI). METHODS Men (n = 43) and women (n = 47), ages 55 to 75 years, were assessed for body mass index, waist-to-hip ratio, waist circumference, and skin folds by anthropometric methods; for percentage of body fat by DXA; and for abdominal total, subcutaneous, and visceral fat by MRI. RESULTS In stepwise regression models, the waist-to-hip ratio explained 50% of the variance in abdominal visceral fat among men (P <.01), and body mass index explained an additional 6% of the variance (P <.01). Among women, waist circumference was the only independent correlate of abdominal visceral fat, accounting for 52% of the variance (P <.01). Among men, the percentage of body fat was the only independent correlate of abdominal subcutaneous fat, explaining 65% of the variance (P <.01). Among women, the percentage of body fat explained 77% of the variance in abdominal subcutaneous fat and body mass index explained an additional 3% (P <.01). CONCLUSIONS Obesity and body composition obtained by readily available anthropometric methods and DXA provide informative estimates of abdominal obesity assessed by MRI imaging.

Relationships of Insulin Sensitivity with Fatness and Fitness and in Older Men and Women

PURPOSE Increased body fatness, especially abdominal obesity, and low levels of fitness are associated with decreased insulin sensitivity. Men and women differ in obesity, body fat distribution, and fitness levels. This cross-sectional study evaluated sex differences in the relationships of insulin sensitivity with fatness and fitness and obesity. METHODS Subjects were nonsmoking, nondiabetic, sedentary men (n = 50) and women (n = 61) aged 55-75 years with mild hypertension. Study measures were insulin sensitivity (QUICKI: 1/[log(fasting insulin) + log(fasting glucose)]), lipids and lipoproteins, total body fatness using dual energy x-ray absorptiometry (DXA), anthropometrics, abdominal obesity using magnetic resonance imaging (MRI), and aerobic fitness assessed as Vo(2) peak during treadmill testing. RESULTS Women had a higher percentage of body fat and more abdominal subcutaneous and less visceral fat than men. Among women, QUICKI correlated negatively with body mass index (BMI), percent body fat, abdominal total fat, subcutaneous fat, and visceral fat but not with lipids. Among men, QUICKI correlated negatively with total and abdominal fatness and triglycerides. QUICKI correlated with fitness in men only. Using stepwise regression, among women, decreased total abdominal fat accounted for 33%, and postmenopausal hormone therapy accounted for an additional 5% of the variance in QUICKI. Among men, only a higher level of fitness independently correlated with insulin sensitivity, accounting for 21% of the variance (p < 0.01). CONCLUSIONS Abdominal obesity among women and fitness among men were the strongest determinants of insulin sensitivity in this older cohort. This raises the question whether there are sex differences in the lifestyle changes that would be most effective in improving insulin sensitivity.

Tricuspid atresia and the Wolff-Parkinson-White syndrome: evaluation methodology and successful surgical treatment of the combined disorders.

to its abolition during intravenous tocainide administration. It seems likely that acceleration of VT rate was induced by tocainide, since in both of our patients their episodic VT had been at constant frequency during observation for 1 month. Although both of these patients had severe underlying heart disease with chronic potentially life-threatening recurrent VT, VF occurred only once in each individual and in each instance in close proximity to initiation of tocainide therapy. Furthermore, VF has not reoccurred since tocainide was discontinued. There were no apparent metabolic or electrolyte abnormalities which might have explained their worsening of ventricular tachyarrhythmias during tocainide. Other antiarrhythmic drugs had been discontinued sufficiently prior to VF to make such change in therapy an important factor. Serum digoxin concentrations were at levels unlikely to be associated with toxic arrhythmias. While a potential interaction between tocainide and digoxin might have resulted in VF, such an event has not been observed with lidocaine, a drug with similar structure and electrophysiologic effects as tocainide. While it ;S not possible to exclude the causal relation of their severe underlying cardiac disease processes or disturbed pharmacokinetics due to related organ system dysfunction, it is not unreasonable to suspect that tocainide was responsible for initiation of VF in these two patients. Unfortunately, tocainide blood levels were not available in both patients. Tocainide is principally removed (45%) by excretion in the urine in unchanged form and 23% is metabolized by carboxylation in the liver. Since our first patient had severe congestive heart failure, impaired excretion might have resulted in toxic blood levels. However, our second patient had normal renal and hepatic function. Based on previous experience with the pharmacokinetics of this highly bioavailable oral drug,‘, 6 it is quite unlikely that our second patient had toxic serum levels. Furthermore, signs and symptoms of CNS or gastrointestinal toxicity were absent in both patients, and these side effects usually occur with high tocainide blood levels.‘,6 Based on these two untoward experiences, we now believe that it is prudent to initiate tocainide therapy in a monitored hospital setting. The drug has proved useful in patients with refractory ventricular tachyarrhythmias and we continue to find tocainide salutary in such patients.

Ventricular tachycardia associated with a left ventricular apex sump aneurysm in an adolescent.

beneficial effects of diltiazem were followed by an associated subjective improvement over an 11-month period.’ In this report we describe a late-stage patient who sustained a significant improvement with nifedipine over a 6-month period. This improvement was associated with a significant change in hemodynamic data measured repeatedly. A white female patient (age 27 years) was admitted for evaluation of progressive dyspnea and syncope on exertion. At the age of 20 years she was known to have cardiomegaly. Her blood pressure was 115/75 mm Hg. There was clinical evidence of right ventricular hypertrophy. On auscultation a loud pulmonic closure sound was followed by a long early diastolic murmur of pulmonary regurgitation. Routine laboratory examinations were normal. The ECG showed right axis deviation and right ventricular hypertrophy. The chest x-ray showed cardiomegaly and central pulmonary arterial dilatation with distal vessel narrowing. A pulmonary angiogram revealed no signs of pulmonary emboli. The most important hemodynamic data are shown in Table I. The pulmonary capillary wedge pressure was normal. After treatment with nifedipine, 20 mg six times a day, significant improvement of hemodynamic data was seen after 3 days. During the follow-up period, symptoms markedly improved. No side effects occurred. Repeated catheterization after 6 months of continued oral therapy showed a sustained beneficial effect (Table I). The results in our patient clearly indicate that further evaluation of nifedipine use in primary pulmonary hypertension is warranted.

ATRIAL PACING TO ESTIMATE SINOATRIAL CONDUCTION TIME IN CHILDREN

Studies in adults have shown a strong correlation between indirect total sinoatrial conduction time (TSACT) using extrastimulus (ES) and atrial pacing (P). No data using P in children exist. To compare P vs. ES, and to examine the effect of different P rates in children, we studied 55 pts.—age 0.2-18.5 yrs—using P and ES. Because children exhibit a wide range of age-related cycle lengths, P was performed using a train of 9 paced right atrial beats normalized to 88-92% (90%),(n=32) or 93-97% (95%),(n=38) of the sinus cycle length (SCL); 15 patients had P determined at both paced cycle lengths. Sinus node (SN) suppression was estimated by recovery CL/SCL × 100(%)(REC). In 13/55 pts ES TSACT was indeterminant. There was no significant difference ([Xmacr ;[plusmn;SD) in SCL (576±152 vs. 574±149 msec), REC (101.9±1.7 vs. 104.4±6.1%), and TSACT (128±40 vs 126±74 msec) (n=26) between ES and P at 90%SCL. ES vs P TSACT correlation was r=0.82 (p<0.001). Similarly with P at 95%SCL, there was no significant difference in SCL (572±129 vs. 576±125 msec), or REC (101.3±1.9 vs. 102.9 ±5.7%); however, TSACT was greater by ES than P (137±38 vs. 105 ± 58 msec; p<0.001) (n=29) with r=0.82 (p<0.001). Intrapatient variation was wide at both pacing rates: coefficient of variance was 33% and 42%, respectively. We conclude that TSACT by P in children, as in adult studies, shows wide intrapatient variability but corresponds well with ES. TSACT by P at 90%SCL approximates ES TSACT in children better than P at 95%SCL perhaps related to more complete SN capture and less pacemaker focus shift. For TSACT by P in children we recommend pacing at 90%SCL.