Danita M. Yoerger

Myocardial Injury and Ventricular Dysfunction Related to Training Levels Among Nonelite Participants in the Boston Marathon

Background— Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction. Methods and Results— We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler–derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, >60% of participants had increased cTnT >99th percentile of normal (>0.01 ng/mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (≥0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL (P<0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r=−0.70, P<0.001) and inversely with training mileage (r=−0.71, P<0.001). Compared with athletes training >45 miles/wk, athletes who trained ≤35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16±5% versus 25±4%, P<0.001), myocyte injury (cTnT 0.09 versus <0.01 ng/mL, P<0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P<0.001). Conclusions— Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.

Familial aggregation in lone atrial fibrillation

Atrial fibrillation (AF) is the most common clinical arrhythmia and a major risk factor for stroke. To investigate the role of genetic factors in a typical clinical population, we determined the extent of familial aggregation in patients with lone AF. To estimate the relative risk to family members, the prevalence of AF for each class of relative was compared to the prevalence in the comparable age and sex group from the general population. Family members had an increased relative risk of AF compared to the general population (risk ratio; 95% confidence intervals): sons (8.1; 2.0–32), daughters (9.5; 1.3–67), brothers (70; 47–102), sisters (34; 14–80), mothers (4.0; 2.5–6.5) and fathers (2.0; 1.2–3.6). Relatives of probands with lone AF are at a substantially increased risk of developing this arrhythmia suggesting a Mendelian genetic contribution to the etiology of this common trait.

Locus for Atrial Fibrillation Maps to Chromosome 6q14–16

Background—Atrial fibrillation (AF), the most common clinical arrhythmia, is a major cause of morbidity and mortality. Although AF is often associated with other cardiovascular conditions, many patients present without an obvious etiology. Inherited forms of AF exist, but the causative gene has been defined only in a single family. We have identified a large family (family FAF‐1) in which AF segregates as a Mendelian trait. Methods and Results—Thirty‐four family members were evaluated by 12‐lead ECG, echocardiogram, 24‐hour Holter monitoring, and laboratory studies. Individuals with electrocardiographically documented AF were defined as affected. Subjects were considered unaffected if they were >60 years of age, had no personal history of AF, and had no offspring with a history of AF. DNA was extracted and genotypic analyses were performed using polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 6, with a peak 2‐point logarithm of the odds (LOD) score of 3.63 (&thetas;=0) at the marker D6S1021. A maximal multipoint LOD score of 4.9 was obtained between D6S286 and D6S1021, indicating odds of ≈100 000:1 in favor of this interval as the location of the gene defect responsible for AF in this family. The LOD scores were robust to changes in penetrance and allele frequency. Haplotype analyses further supported this minimal genetic interval. Conclusion—We have mapped a novel locus for AF to chromosome 6q14‐16. The identification of the causative gene in this interval will be an important step in understanding the fundamental mechanisms of AF. (Circulation. 2003;107: 2880‐2883.)

Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5–6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between ≈3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease.

Pathological effects of alcohol septal ablation for hypertrophic obstructive cardiomyopathy

Background: The pathological effects and the mechanisms of action of intracoronary administration of ethanol for alcohol septal ablation (ASA) for the management of hypertrophic obstructive cardiomyopathy (HOCM) are unknown. Methods: We examined surgical specimens and, in one case, autopsy specimens from four patients who underwent surgical septal myectomy 2 days to 14 months after unsuccessful ASA. Results: Pathological examination early after ASA showed coagulative necrosis of both the myocardium and the septal perforator arteries. Affected arteries were distended and occluded by necrotic intraluminal debris, without platelet–fibrin thrombi. Late after unsuccessful ASA, excised septal tissue was heterogeneous, containing a region of dense scar, and adjacent tissue containing viable myocytes and interspersed scar. Conclusions: Intracoronary administration of ethanol in patients with HOCM causes acute myocardial infarction with vascular necrosis. The coagulative necrosis of the arteries, their distension by necrotic debris and the absence of platelet–fibrin thrombi distinguish ethanol-induced infarction from that caused by atherosclerotic coronary artery disease. The direct vascular toxicity of ethanol may be an important aspect of the mechanism of successful ASA.

Overlapping sequential pulses. A new waveform for transthoracic defibrillation.

BACKGROUND A directionally changing shock electrical vector could facilitate defibrillation by depolarizing myocytes with different orientations vis-à-vis the shock field. Such a changing vector can be achieved by a new waveform for transthoracic defibrillation: overlapping sequential pulses. Our purpose was to evaluate this waveform. METHODS AND RESULTS Ventricular fibrillation was induced in closed-chest dogs. Single and overlapping truncated exponential waveform pulse shocks were then administered from self-adhesive chest electrodes. Single pulse (control) shocks were 7.5-millisecond duration, while the sequential overlapping pulse shocks, using two different pathways, consisted of two pulses, each 5.0-millisecond duration; the second pulse began 2.5 milliseconds after the start of the first pulse and ended 2.5 milliseconds after the end of the first pulse. Thus, the total duration of the sequential overlapping shock was 7.5 milliseconds. During the overlap phase (2.5 milliseconds), the electrical vector orientation is the summation of the individual vectors. Two different electrode placements and corresponding electrical vector orientations were studied: group 1 (n = 14), left lower chest to right upper chest (pulse 1), overlapped by right lower chest to left upper chest (pulse 2), with the sequence then reversed; and group 2 (n = 11), left chest to right chest (pulse 1) overlapped by dorsal (vertebral column) to ventral (sternum) (pulse 2) with the sequence then reversed. At voltages equivalent to energies of 50, 100, and 150 J, the sequential overlapping pulse shocks achieve higher success rates than the single pulse shocks: At the low energy, 50 J, single pulse shock success rates were 0% (group 2) and 14% (group 1), while the overlapping pulse shocks achieved success rates of 39% (group 2) and 55% (group 1) (P < .05). Similarly, at the highest energy tested, 150 J, single pulse shock success rates were 45% (group 2) and 61% (group 1), while the overlapping pulse shock success was 91% (group 2) and 95% (group 1) (P < .05). In a third group of dogs (n = 3), intracardiac plunge electrodes placed orthogonally in the septum showed that the orthogonal components of intracardiac voltage gradient change varied markedly during the three phases of the sequential overlapping shocks, demonstrating the changing direction of the net electrical vector as the shock proceeded. In a fourth group of dogs (n = 5), short-duration (2.5-millisecond) single pulse shocks were compared with longer 7.5-millisecond single pulse shocks and with the sequential overlapping pulse shocks, all at equivalent energies. Despite substantially higher current flow, the 2.5-millisecond-duration single pulse shocks were not more effective than 7.5-millisecond single pulse shocks, and both 2.5- and 7.5-millisecond duration single pulse shocks had markedly inferior success rates compared with the sequential overlapping pulse shocks. CONCLUSIONS Sequential overlapping pulse shock waveforms facilitate defibrillation compared with single pulse shocks of the same total energy. This is due at least in part to the changing orientation of the electrical vector during the multiple pulse shock.

Effect of Electrode Position and Gel-Application Technique on Predicted Transcardiac Current During Transthoracic Defibrillation

STUDY OBJECTIVE In transthoracic defibrillation, the American Heart Association (AHA) recommends wide separation of electrodes and avoidance of gel smearing between electrodes. Few data support this recommendation. Our objective was to determine the importance of electrode placement and gel-application technique on transcardiac defibrillation current and the effect of changes caused by postexercise vasodilation and sweating. METHODS Our subjects were 10 normal adults, 5 men and 5 women, who ranged in age from 22 to 48 years. We determined interelectrode impedance (Z) using a validated test-pulse method that does not require shock delivery. Electrode placement/gel-application techniques were varied among four types: (1) AHA-recommended technique (apex-to-anterior electrode placement, no smearing of gel between electrodes); (2) parasternal-to-anterior placement, electrodes within 2 cm of each other, no smearing of gel between electrodes; (3) parasternal-to-anterior placement, electrodes within 2 cm of each other with smearing of gel between electrodes (worst-case scenario); and (4) apex-to-anterior placement, smearing of gel between electrodes. To assess the effect of cutaneous vasodilation and sweating on interelectrode impedance, we repeated these measurements after the subjects performed 12 to 18 minutes of treadmill exercise. The ratio of predicted transcardiac current of the AHA technique to that of the nonstandard technique was estimated with this formula: square root of Z, non-standard technique divided by square root of Z, AHA technique. RESULTS Resting interelectrode impedance declined 38% from 58 +/- 10.3 omega (AHA-recommended technique) to 36 +/- 7.6 omega (electrode paddles adjacent, gel smeared between) (P < .01). Predicted transcardiac current ratio was reduced to .78 +/- .09 (P < .01), a 22% reduction. We noted no change in the results after exercise. CONCLUSION Adjacent placement of electrodes and smearing of gel between electrodes creates a low-impedance pathway along the chest wall, which shunts current away from the heart. Thus improper application of electrodes and gel substantially degrades transcardiac current and may result in failed defibrillation. Sweating and vasodilation did not cause a similar problem.

Covered Stent Septal Ablation for Hypertrophic Obstructive Cardiomyopathy Initial Success but Ultimate Failure Resulting From Collateral Formation

A 76-year-old woman had syncope and exertional dyspnea. A systolic murmur was noted. An echocardiogram showed hypertrophic obstructive cardiomyopathy, with septal thickness 18 mm and peak left ventricular outflow tract (LVOT) gradient 78 mm Hg (Figure 1A). Coronary arteriography demonstrated mild coronary atherosclerosis, with mild stenosis of the proximal left anterior descending (LAD) coronary artery involving the first septal branch creating an unfavorable angle of entry into this branch (Figure 2A). Attempts to catheterize the first septal branch with an angioplasty balloon catheter for intracoronary …A 76-year-old woman had syncope and exertional dyspnea. A systolic murmur was noted. An echocardiogram showed hypertrophic obstructive cardiomyopathy, with septal thickness 18 mm and peak left ventricular outflow tract (LVOT) gradient 78 mm Hg (Figure 1A). Coronary arteriography demonstrated mild coronary atherosclerosis, with mild stenosis of the proximal left anterior descending (LAD) coronary artery involving the first septal branch creating an unfavorable angle of entry into this branch (Figure 2A). Attempts to catheterize the first septal branch with an angioplasty balloon catheter for intracoronary …

Images in cardiovascular medicine. Covered stent septal ablation for hypertrophic obstructive cardiomyopathy: initial success but ultimate failure resulting from collateral formation.

A 76-year-old woman had syncope and exertional dyspnea. A systolic murmur was noted. An echocardiogram showed hypertrophic obstructive cardiomyopathy, with septal thickness 18 mm and peak left ventricular outflow tract (LVOT) gradient 78 mm Hg (Figure 1A). Coronary arteriography demonstrated mild coronary atherosclerosis, with mild stenosis of the proximal left anterior descending (LAD) coronary artery involving the first septal branch creating an unfavorable angle of entry into this branch (Figure 2A). Attempts to catheterize the first septal branch with an angioplasty balloon catheter for intracoronary …A 76-year-old woman had syncope and exertional dyspnea. A systolic murmur was noted. An echocardiogram showed hypertrophic obstructive cardiomyopathy, with septal thickness 18 mm and peak left ventricular outflow tract (LVOT) gradient 78 mm Hg (Figure 1A). Coronary arteriography demonstrated mild coronary atherosclerosis, with mild stenosis of the proximal left anterior descending (LAD) coronary artery involving the first septal branch creating an unfavorable angle of entry into this branch (Figure 2A). Attempts to catheterize the first septal branch with an angioplasty balloon catheter for intracoronary …

Compassionate use of the amplatzer ASD closure device for residual postinfarction ventricular septal rupture following surgical repair

We report successful transcatheter closure of a post‐MI ventricular septal rupture acutely following unsuccessful surgical repair. Catheter closure was accomplished by the use of a 26‐mm Amplatzer atrial septal occluder. Initial attempts to close the defect with the use of 28‐mm and 33‐mm CARDIOSEAL were unsuccessful. Closure technique, immediate and long‐term follow‐up outcomes are reported. Cathet Cardiovasc Intervent 2003;59:230–233.