Helmut Roskamm

A Comparison of Surgical and Medical Therapy for Atrial Septal Defect in Adults

BACKGROUND The surgical closure of an atrial septal defect is frequently recommended for patients over 40 years of age. However, the prognosis for such patients with unrepaired defects is largely unknown, and the outcome for patients operated on after the fourth decade of life has not yet been compared with that for medically treated patients in a controlled follow-up study. METHODS In a retrospective study, we examined the clinical course of 179 consecutive patients with isolated atrial septal defects diagnosed after the age of 40. The 84 patients (47 percent) who underwent surgical repair were compared with the 95 patients (53 percent) who were treated medically. The mean (+/-SD) follow-up period was 8.9 +/- 5.2 years (range, 1 to 26). RESULTS Multivariate analysis revealed that surgical closure of the defect significantly reduced mortality from all causes (relative risk, 0.31; 95 percent confidence interval, 0.11 to 0.85). The adjusted 10-year survival rate of surgically treated patients was 95 percent, as compared with 84 percent for the medically treated patients. In addition, surgical treatment prevented functional deterioration, as measured by the New York Heart Association class (relative risk, 0.21; 95 percent confidence interval, 0.08 to 0.55). However, the incidence of new atrial arrhythmias or of cerebrovascular insults in the two groups was not significantly different. CONCLUSIONS The surgical repair of an atrial septal defect in patients over 40 years of age, as compared with medical therapy, increases long-term survival and limits the deterioration of function due to heart failure. However, surgically treated patients should be followed closely for the onset of atrial arrhythmias so as to reduce the risk of thromboembolic complications.

Inflammation and Long-Term Mortality After Non–ST Elevation Acute Coronary Syndrome Treated With a Very Early Invasive Strategy in 1042 Consecutive Patients

Background—This study sought to evaluate the predictive value of C-reactive protein (CRP) on long-term mortality in non–ST-elevation acute coronary syndromes (NSTACS) that were treated with a very early aggressive revascularization strategy. Methods and Results—We conducted a prospective cohort study in 1042 consecutive patients with NSTACS who were undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 hours. Levels of CRP were determined on admission. The patients were followed for a mean of 20 months. In-hospital mortality was significantly higher in patients with a CRP>10 mg/L (3.7% versus 1.2% with CRP<3 mg/L and versus 0.8% with CRP of 3 to 10 mg/L; relative risk for CRP>10 mg/L compared with CRP≤10 mg/L was 4.2, 95% confidence interval [CI] was 1.6 to 11.0;P =0.004). The increase in mortality in patients with CRP>10 mg/L persisted during follow-up. Long-term mortality was 3.4% with CRP<3 mg/L, 4.4% with CRP between 3 and 10 mg/L, and 12.7% with CRP>10 mg/L (relative risk for CRP>10 mg/L compared with CRP≤10 mg/L, 0.8; 95% CI, 2.3 to 6.2;P <0.001). In addition, Kaplan-Meier survival analysis demonstrated a significantly reduced survival at 4 years in patients with a CRP>10 mg/L (78% versus 88% for a CRP of 3 to 10 mg/L and versus 92% for CRP<3 mg/L;P <0.001 by log-rank). In a multivariate analysis, CRP was an independent predictor of long-term mortality. Patients with a CRP>10 mg/L had >4 times the risk of death (odds ratio, 4.1; 95% CI, 2.3 to 7.2). Conclusion—CRP is a strong independent predictor of short and long-term mortality after NSTACS that are treated with very early revascularization.

Effect of breathing rate on oxygen saturation and exercise performance in chronic heart failure

BACKGROUND In chronic heart failure (CHF), impaired pulmonary function can independently contribute to oxygen desaturation and reduced physical activity. We investigated the effect of breathing rate on oxygen saturation and other respiratory indices. METHODS Arterial oxygen saturation (SaO2) and respiratory indices were recorded during spontaneous breathing (baseline) and during controlled breathing at 15, six, and three breaths per min in 50 patients with CHF and in 11 healthy volunteers (controls). 15 patients with CHF were randomly allocated 1 month of respiratory training to decrease their respiratory rate to six breaths per min. Respiratory indices were recorded before training, at the end of training, and 1 month after training. FINDINGS During spontaneous breathing, mean SaO2 was lower in CHF patients than in controls (91-4% [SD 0.4] vs 95.4% [0.2], p<0.001). Controlled breathing increased SaO2 at all breathing rates in patients with CHF. Compared with baseline, minute ventilation increased at 15 breaths per min (+45.9% [9.8], p<0.01), did not change at six breaths per min, and decreased at three breaths per min (-40.3% [4.8], p<0.001). In the nine CHF patients who had 1 month of respiratory training, resting SaO2 increased from 92.5% (0.3) at baseline to 93.2% (0.4) (p<0.05), their breathing rate per min decreased from 13.4 (1.5) to 7.6 (1.9) (p<0.001), peak oxygen consumption increased from 1157 (83) to 1368 (110) L/min (p<0.05), exercise time increased from 583 (29) to 615 (23) min/s (p<0.05), and perception of dyspnoea reduced from a score of 19.0 (0.4) to 17.3 (0.9) on the Borg scale (p<0.05). There were no changes in the respiratory indices in the patients who did not have respiratory training. INTERPRETATION Slowing respiratory rate reduces dyspnoea and improves both resting pulmonary gas exchange and exercise performance in patients with CHF.

Interval training in patients with severe chronic heart failure : analysis and recommendations for exercise procedures

This study analyzes a new exercise training procedure, which includes interval exercise training on cycle ergometer (IntCT) (30-s work phases/60-s recovery phases) and on treadmill (60-s work and recovery phases each). Training was applied for 3 wk in 18 patients with severe chronic heart failure (CHF) ((mean +/- SEM) age 52 +/- 2 yr, ejection fraction 21 +/- 1%). Peak VO2 was increased from 12.2 +/- 0.7 to 14.6 +/- 0.7 ml-kg-1 min-1 owing to training (P < 0.001). A specific steep ramp test (work rate increments 25 W.10 s-1) was developed to derive exercise intensity for work phases in IntCT, which was 50% of the maximum work rate achieved. Steep ramp test was performed at the start of the study to determine the initial training work rate, then weekly to readjust it. Since the maximum work rate achieved from this test increased weekly (144 +/- 10 W -->172 +/- 10 W-->200 +/- 11 W; P < 0.001), the training work rate also increased (72 +/- 4 W-->86 +/- 6 W-->100 +/- 7 W; P < 0.001). Physical responses to IntCT were measured. There was no significant change in heart rate, blood pressure, and ratings of perceived exertion (RPE) using a Borg Scale between the first and the third week of training (heart rate 88 +/- 3 b.min-1; blood pressure 115 +/- 4/80 +/- 2 mm Hg; leg fatigue 12 +/- 1; dyspnea 10 +/- 1). Mean lactate concentration (1.70 +/- 0.09 mmol-1-1) indicated an overall aerobic range of training intensity. When compared with the commonly used intensity level of 75% peak VO2 from an ordinary ramp test (work rate increments 12.5 W.min-1), the performed training work rate was more than doubled (240%; P < 0.0001) while cardiac stress was lower (86%; P < 0.01). Values of norepinephrine and epinephrine as well as of RPE corresponded to those measured at 75% peak VO2. Interval exercise training is thus recommended for selected patients with CHF as it allows intense exercise stimuli on peripheral muscles with minimal cardiac strain. Using a steep ramp test, training work rate can be determined and readjusted weekly during initial training period.

Exercise testing provides additional prognostic information in angiographically defined subgroups of patients with coronary artery disease.

We examined whether exercise testing with measurement of cardiac output during maximal exercise can provide additional prognostic information for medically treated patients in whom left ventricular function and extent of coronary artery disease are known. We followed 1034 patients with normal or mildly impaired left ventricular function; 410 of these patients (group 1) had single-vessel disease, 316 had double-vessel disease (group 2), and 308 had triple-vessel disease (group 3). In addition, 204 patients with double- or triple-vessel disease and moderately impaired left ventricular function (group 4) were followed. Mean follow-up in these 1238 patients was 4.5 years. End point of follow-up was death. Groups 1, 2, and 3 were divided into terciles according to the maximally achieved values of the following exercise variables: exercise tolerance, angina-free exercise tolerance, maximal heart rate, and cardiac output during maximal exercise. Group 4 was divided into halves accordingly. Survival curves (according to the method of Cutler and Ederer) for group 2 showed a 15% difference in 5 year survival rate between the highest and lowest terciles (p less than .005) by use of the noninvasive variables exercise tolerance, angina-free exercise tolerance, and maximal heart rate (95% vs 80%). The separation into terciles according to cardiac output during maximal exercise resulted in a significant difference in survival rates between the highest and lowest terciles (halves) in all groups of patients. The differences in 5 year survival rates were 9% (p less than .05), 16% (p less than .05), and 19% (p less than .005) for groups 1, 2, and 3, respectively, and 22% for group 4 (p less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental pain thresholds and plasma beta-endorphin levels during exercise

Experimental pain thresholds (electrical intracutaneous finger and dental pulp stimulation) and plasma hormone levels (beta-endorphin, cortisol, and catecholamines) were measured in ten healthy sportive men before, during, and after progressively more strenuous physical exercise. In a double-blind study conducted on two different days, 20 mg of the opioid-antagonist naloxone or placebo was administered prior to exercise. A significant pain threshold elevation was found during exercise for finger (ANOVA, P less than 0.004) and dental pulp stimulation (P less than 0.01). Pain threshold elevation was most pronounced during maximal exertion, at which time the subjects reported the greatest subjective fatigue. Thresholds remained elevated 10-15 min after the end of exercise, and, 60 min after exercise, thresholds returned to baseline values. The subjective magnitude estimation of suprathreshold stimuli was significantly reduced (P less than 0.0001) 5-10 min after exercise. Plasma beta-endorphin, cortisol, and catecholamines increased significantly (P less than 0.0005, all values) during exercise. Plasma beta-endorphin levels did not correlate significantly with pain thresholds (r = -0.37, NS). Naloxone failed to affect pain thresholds, although beta-endorphin and cortisol increased significantly more (P less than 0.02) during exercise after naloxone. It is concluded that short-term, exhaustive physical exercise can evoke a transient elevation in pain thresholds. This exercise-induced elevation in pain threshold does not, however, appear to be directly related to plasma endorphin levels.

Women do have an improved long-term outcome after non–ST-elevation acute coronary syndromes treated very early and predominantly with percutaneous coronary intervention: A prospective study in 1,450 consecutive patients

OBJECTIVES This study sought to assess gender-based differences in long-term outcome after very early aggressive revascularization for non-ST-elevation acute coronary syndromes (NSTACS). BACKGROUND The Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC) II study suggested that women have less to gain from an early invasive strategy. METHODS We conducted a prospective cohort study in 1,450 consecutive patients with NSTACS undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularization strategy within 24 h of admission. The combined primary end point was defined as death or nonfatal myocardial infarction (MI) and recorded for a mean of 20 months. RESULTS Percutaneous coronary intervention was performed in more than 50% of patients in women and men and accompanied with stenting in 80%. The percutaneous coronary intervention:coronary artery bypass grafting ratio was 4:1 in men and 5:1 in women. The primary end point occurred in 29 (7.0%) women as compared with 108 (10.5%) men (hazard ratio for women, 0.65; 95% confidence interval [CI] 0.42 to 0.99; p = 0.045). Backward-stepwise multivariate Cox regression analysis identified female gender as an independent predictor of death or MI (hazard ratio for female gender, 0.51; 95% CI, 0.28 to 0.92; p = 0.024). Kaplan-Meier analysis showed that women had consistently lower event rates during the entire follow-up period (p = 0.037 by log-rank for death or MI). CONCLUSIONS Women treated with very early aggressive revascularization with coronary stenting of the culprit lesion as the primary revascularization strategy have a better long-term outcome as compared with men.

Stent-Supported Angioplasty of Severe Atherosclerotic Renal Artery Stenosis Preserves Renal Function and Improves Blood Pressure Control: Long-Term Results from a Prospective Registry of 456 Lesions

Purpose: To report a prospective study evaluating the long-term impact of stent-supported angioplasty on renal function and blood pressure control. Methods: In a 6-year period, 456 hemodynamically significant de novo renal artery stenoses ≥70% were treated in 340 consecutive hypertensive patients (223 men; mean age 66±10 years, range 44–84) with or without impaired renal function. Baseline data on serum creatinine (sCr), intrarenal resistance index, ambulatory 24-hour blood pressure monitoring, and documentation of the number and dose of antihypertensive drugs were compared to values obtained during follow-up. The primary endpoint was a 10% decrease in sCr; the glomerular filtration rate and changes in blood pressure control were additional outcome measures. Results: During a mean follow-up of 34±20 months, sCr decreased significantly from 1.45±0.87 to 1.39±0.73 mg/dL (p=0.048). In 34% of the patients, sCr decreased >10%, 39% were unchanged, and 27% had an increase >10%. Glomerular filtration rate increased from 59±26 to 62±26 mL/min/1.73 m2 (p=0.6). Systolic, diastolic, and mean blood pressure measurements significantly improved immediately after the intervention (132/72/93 versus 144/79/102 mmHg at baseline, p<0.0001) and remained improved during follow-up (p<0.0001). Blood pressure control was improved in 46%, unchanged in 43%, and deteriorated in 11%. Baseline sCr, bilateral intervention, percent diameter stenosis, and 3-vessel coronary disease were independent predictors of improved renal function during follow-up; the number of antihypertensive drugs taken before the intervention predicted improved blood pressure control. Conclusions: Stent-supported angioplasty of renal artery stenoses preserves renal function and improves blood pressure control in a broader spectrum of patients than previously thought.

Ultrasound-Guided Strategy for Provisional Stenting With Focal Balloon Combination Catheter: Results From the Randomized Strategy for Intracoronary Ultrasound-Guided PTCA and Stenting (SIPS) Trial

BackgroundIntracoronary ultrasound (ICUS) has provided insights into vascular pathology and interventional therapy. The Strategy for ICUS-Guided PTCA and Stenting (SIPS) trial tested the hypothesis that routine ICUS guidance of coronary interventions improves outcome. Methods and ResultsA single-center consecutive-patient randomized design (with 6-month angiographic and 2-year clinical follow-up) was used. Consecutive patients (no chronic total occlusions or emergency procedures) were randomized to ICUS-guided provisional stenting or standard angiographic guidance. Quantitative angiographic minimal lumen diameter (MLD), angiographic restenosis, clinically driven target lesion revascularization, and major adverse cardiac events (MACEs) were evaluated. A total of 291 procedures (356 lesions) were included. Procedure success was higher in the ICUS-guided group than the group randomized to standard guidance (94.7% versus 87.4%, respectively;P =0.033), whereas time (65.2±31.0 versus 60.5±34.0 minutes, P =0.18) and contrast use (209.3±94.1 versus 197.5±89.5 mL, P =0.23) were not significantly different. Stenting rates were similar (49.7% versus 49.5%, P =0.89). Acute gain was greater in the ICUS-guided group than in the standard guidance group (1.85±0.72 versus 1.67±0.76 mm, respectively;P =0.02). Angiographic 6-month analysis revealed no difference in MLD (1.71±0.94 versus 1.57±0.90, P =0.19) or binary restenosis rate (>50% diameter stenosis) (29% versus 35%, P =0.42). Clinical follow-up (602±307 days) showed a significant decrease in clinically driven target lesion revascularization in the ICUS group compared with the standard guidance group (17% versus 29%, respectively;P =0.02). ConclusionsAlthough angiographic MLD did not differ significantly after 6 months, ICUS-guided provisional stenting improved 2-year clinical results after intervention.

Baroreceptor stimulation: Pain perception and sensory thresholds

Baroreceptor activity has been implicated in the modulation of pain. Sensory detection thresholds and pain ratings were measured in a group of 28 men during carotid baroreceptor manipulation with the PRES (phase-related external suction) neck suction technique. Brief, cardiac phase-related electrical impulses were delivered intracutaneously to the finger. The results indicate that minimum baroreceptor activity was associated with more severe pain, but had no effect on sensory detection threshold. The results are discussed in terms of the learned model of hypertension.