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Biomedical subjects

Mark S Link

Publications and source records attributed to Mark S Link.

At least 19 recordsLinked to original sources

Commotio cordis--sudden cardiac death with chest wall impact.

Commotio cordis (CC), sudden death as a result of a blunt, often innocent-appearing chest wall blow, is being reported with increasing frequency. The clinical spectrum is diverse; however, a substantial number of cases occur in youth athletics. In events that occur during sport, victims are struck by projectiles regarded as standard implements of the game. Sudden death is instantaneous and victims are most often found in ventricular fibrillation (VF). Overall survival is poor; however, successful resuscitation can be achieved with early defibrillation. Autopsy is notable for the absence of any significant cardiac or thoracic injury. Development of an experimental model has allowed for substantial insights into the underlying mechanisms of sudden death. In anesthetized juvenile swine, induction of VF is instantaneous following chest wall blows occurring during a vulnerable window before the T wave peak. Crucial variables including the velocity of impact, impact location, and hardness of the impact object have been identified. Rapid left ventricular (LV) pressure rise following chest impact likely results in activation of ion channels via mechano-electric coupling. The generation of inward current via mechano-sensitive ion channels likely results in augmentation of repolarization and nonuniform myocardial activation, and is the cause of premature ventricular depolarizations that are triggers of VF in CC. While softer-than-standard safety baseballs reduce the risk of CC, commercially available chest protectors are ineffective in preventing CC. The development of more effective chest protectors and more widespread use of automated external defibrillators at youth sporting events are needed.

Death, Sudden, Cardiac↗

Importance of the autonomic nervous system in an experimental model of commotio cordis.

BACKGROUND: Young athletes may die suddenly when they are struck in the chest (commotio cordis). Proposed mechanisms of sudden death in commotio cordis include hypervagatonia and activation of the sympathetic nervous system. In an experimental model of commotio cordis, the importance of the sympathetic and parasympathetic nervous system in the initiation of ventricular fibrillation was evaluated. MATERIAL/METHODS: Juvenile swine weighing between 8 and 12 kg were anesthetized with ketamine and isoflurane and placed prone in a sling. Twenty animals were randomized to pretreatment with placebo or sympathetic and parasympathetic blockade. Chest blows were guided by echocardiography to the center of the left ventricle and animals received 1-3 strikes with a regulation baseball propelled at 30 mph and timed to impact 10-30 ms prior to the peak of the T-wave. RESULTS: With 17 impacts in 10 autonomically blocked animals, 6 episodes of ventricular fibrillation were seen; with 15 impacts in 10 control animals, ventricular fibrillation occurred 6 times. There was also no significant difference between the groups in occurrence of nonsustained polymorphic ventricular tachycardia or ST elevation. Transient complete heart block was less commonly seen in animals treated with autonomic blockade, although this did not achieve statistical significance. CONCLUSIONS: In this experimental model of commotio cordis, autonomic blockade did not affect the frequency of sudden cardiac death, polymorphic ventricular tachycardia or ST segment elevation. Thus, vagotonic and sympathetic surges likely do not contribute to the syndrome of sudden death due to chest blows in young people and athletes.

Animals↗

Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction.

BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (HCM) has been regarded as the predominant hemodynamic form of the disease on the basis of assessment of outflow gradient under resting conditions. We sought to prospectively define the prevalence, clinical profile, and significance of left ventricular (LV) outflow tract obstruction under resting conditions and with physiological exercise in a large HCM cohort. METHODS AND RESULTS: We prospectively analyzed 320 consecutive HCM patients (age, 47+/-17 years), measuring LV outflow gradient at rest, with Valsalva maneuver, and with exercise echocardiography. LV outflow obstruction was present at rest and/or with exercise in 225 patients (70%); 119 had rest gradients > or = 50 mm Hg and were not exercised. Of the other 201 patients with gradients < 50 mm Hg at rest (average, 4+/-9 mm Hg), 106 developed mechanical obstruction to LV outflow resulting from mitral valve-septal contact after exercise (80+/-43 mm Hg), including 76 with marked gradients > or = 50 mm Hg and 46 with heart failure symptoms. The remaining 95 patients (30%) had no or small gradients (< 30 mm Hg) both at rest and with exercise. Valsalva maneuver underestimated the presence and magnitude of exercise-induced obstruction. CONCLUSIONS: Among those patients who come to clinical evaluation, HCM is a predominantly obstructive disease in which LV outflow gradients, frequently associated with heart failure symptoms and often identified only with exercise, are evident in most patients (ie, 70%). Identification of LV outflow obstruction with exercise echocardiography may broaden management options in HCM by identifying symptomatic patients not otherwise regarded as potential candidates for septal reduction therapy. Assessment of subaortic gradients with exercise should be a routine component of the evaluation of HCM patients without outflow obstruction under resting conditions.

Adult↗

Treatment crossovers did not affect randomized treatment comparisons in the Mode Selection Trial (MOST).

OBJECTIVES: We evaluated the impact of treatment crossovers on study results in the Mode Selection Trial (MOST). BACKGROUND: The MOST study, a 2,010-patient, 6-year trial comparing dual-chamber pacing (DDDR) and ventricular pacing (VVIR) in sinus node dysfunction, demonstrated no difference in death or stroke and modest reductions in heart failure hospitalization (HFH) and atrial fibrillation (AF) with DDDR pacing. However, a moderate proportion of VVIR-randomized patients were temporarily or permanently crossed over to DDDR pacing. METHODS: Intent-to-treat (ITT) analyses compared treatment arms by randomized pacing mode. On-treatment analyses used time-dependent covariates to account for all crossovers. All analyses used Cox proportional hazards models and included covariates prespecified in the study design: age, gender, Charlson index, and prior stroke, heart failure, myocardial infarction, supraventricular tachyarrhythmia, and ventricular tachycardia or fibrillation. RESULTS: Of 996 VVIR-randomized patients, 375 (38%) were DDDR paced at some time, accounting for 27% of follow-up days among all VVIR-randomized patients. Of 1,014 DDDR-randomized patients, 53 (5%) were VVIR paced at some time, accounting for 1.5% of follow-up days among all DDDR-randomized patients. On-treatment analyses showed slightly lower hazard ratios favoring DDDR versus VVIR compared with ITT: death or stroke 0.88 (on-treatment) versus 0.91 (ITT); death 0.94 versus 0.95; stroke 0.74 versus 0.81; HFH 0.72 versus 0.73; and AF 0.72 versus 0.77. Interpretation of treatment effects was unchanged. CONCLUSIONS: Although treatment crossovers accounted for >25% of follow-up time in the VVIR-randomized group, this did not affect study results. End point comparisons between randomized modes are accurate reflections of DDDR versus VVIR pacing in this study population.

Aged↗

A public access defibrillation programme in non-inpatient hospital areas.

INTRODUCTION: Automatic external defibrillators (AED) have proven to be valuable and life saving for out of hospital cardiac arrests. Their use in hospital arrests is less well documented, but they offer the opportunity to improve survival in the hospital setting also. METHODS: The implementation of a public access defibrillation (PAD) programme at a tertiary care hospital is described, with reference specifically to targeting areas where time from arrest to arrival of defibrillation would be greater than 3 min. RESULTS: Nine AEDs were placed in areas of the hospital distant from inpatient or outpatient floors. The locations of the AEDs were chosen based on a 3 min walk from currently available defibrillators to all areas of the hospital, including parking garages and walkways from building to building. In this programme AED use in non-inpatient hospital locations resulted in the resuscitation of a patient in ventricular fibrillation. CONCLUSION: PAD in non-inpatient hospital settings can be life saving and similar programmes should be considered for other hospitals.

Boston↗

Failure of commercially available chest wall protectors to prevent sudden cardiac death induced by chest wall blows in an experimental model of commotio cordis.

OBJECTIVE: Sudden cardiac death that results from chest wall blows (commotio cordis) the second leading cause of death in young athletes. Most events are caused by blows from projectiles, such as baseballs or lacrosse balls, with a substantial proportion occurring despite the use of a chest protector. In the present experiment, we tested the effectiveness of commercially available chest protectors in preventing ventricular fibrillation (VF) that results from chest wall strikes with baseballs and lacrosse balls. METHODS: Twelve different baseball or lacrosse chest protectors were evaluated in juvenile swines that were subjected to 40-mph baseball or lacrosse ball blows to the precordium during the vulnerable period of repolarization for VF and were compared with control impacts without chest protectors. Seven baseball chest protectors were hit by regulation baseballs, and 5 lacrosse chest protectors were tested by blows with standard lacrosse balls. Each animal received 2 chest blows for each protector and 2 control impacts without a chest protector, with the sequence of impacts assigned randomly. RESULTS: VF was elicited by 12 (32%) of 37 strikes in control animals without baseball chest protectors. None of the baseball chest wall protectors tested were shown to decrease significantly the occurrence of VF when compared with controls. VF was elicited by 11 (46%) of 24 strikes in control animals without lacrosse chest protectors. None of the lacrosse chest wall protectors tested decreased significantly the occurrence of VF when compared with controls. CONCLUSION: In our experimental animal model of commotio cordis, commercially available baseball and lacrosse chest wall protectors were ineffective in protecting against VF that was triggered by chest blows and, by inference, sudden cardiac death. Improvements in materials and design of chest wall barriers are necessary to reduce the occurrence of these tragic events and make the athletic field safer for youths.

Adolescent↗

Equivalent arrhythmic risk in patients recently diagnosed with dilated cardiomyopathy compared with patients diagnosed for 9 months or more.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) recently expanded coverage for implantable cardioverter-defibrillators (ICDs) in patients with left ventricular ejection fraction < or =35% and nonischemic dilated cardiomyopathy for > or =9 months. To investigate the ramifications of these criteria, the ICD registry from Tufts-New England Medical Center was analyzed for arrhythmic events and death in patients with newly diagnosed (<9 months) vs late-diagnosed (> or =9 months) nonischemic dilated cardiomyopathy. OBJECTIVES: The purpose of this study was to analyze the arrhythmic risk in patients with recent vs late diagnosis of nonischemic dilated cardiomyopathy. METHODS: One hundred thirty-one patients with nonischemic dilated cardiomyopathy were divided into two cohorts (<9 or > or =9 months of symptoms) and analyzed for any occurrence of treated ventricular arrhythmia, potentially lethal arrhythmias defined as ventricular flutter rates > or =230 bpm, and ventricular fibrillation. Patients with documented sustained ventricular tachycardias (included in prior CMS coverage) were excluded. RESULTS: In the study group, the mean age was 58.1 +/- 15 years and ejection fraction 20.6% +/- 8%. In a follow-up period of 25.3 +/- 24 months, the 52 patients with a recent diagnosis (1.4 +/- 2 months) had no difference in the occurrence of ventricular arrhythmias (P = .49) and malignant ventricular arrhythmias (P = .16) compared with the 79 patients diagnosed > or =9 months (mean 58.1 +/- 39 months). CONCLUSION: Patients with nonischemic dilated cardiomyopathy experienced equivalent occurrences of treated and potentially lethal arrhythmias irrespective of diagnosis duration. These findings suggest that the 9-month time qualifier used in the CMS guidelines for ICD reimbursement may not reliably discriminate patients at high risk for sudden cardiac death in this selected population.

Adult↗

High risk of ventricular arrhythmias in patients with nonischemic dilated cardiomyopathy presenting with syncope.

It is not entirely clear whether the presentation of syncope in patients with nonischemic dilated cardiomyopathy (NIDC) is an ominous prognostic indicator, because randomized controlled implantable cardioverter-defibrillator (ICD) trials generally exclude such patients. This study compared 108 consecutive patients with NIDC presenting with syncope with 71 consecutive patients with NIDC who presented with sustained ventricular arrhythmias, with regard to freedom from any ventricular arrhythmias or life-threatening arrhythmias and all-cause mortality. There was no significant difference between the groups in the 3 outcomes during the follow-up of 43.5 +/- 32.1 months. Male gender and ICD therapy predicted increased risk for any ventricular arrhythmias. A reduced left ventricular ejection fraction and increased age were predictive of increased mortality. In conclusion, patients with NIDC presenting with syncope are a high-risk group, with event rates similar to patients with NIDC presenting with sustained arrhythmias, and should be considered for ICD therapy.

Aged↗

Cryoablation of the pulmonary veins using a novel balloon catheter.

INTRODUCTION: Pulmonary vein (PV) isolation has emerged as a promising technique for the treatment of patients with drug-refractory atrial fibrillation, however, the achievement of transmural lesions has remained a challenge. We evaluated the ability of a novel balloon-based cryogenic catheter system in achieving transmural lesions for PV isolation. METHODS: Six pulmonary vein ostia from three excised ovine hearts and lungs were used in this study. The balloon catheter was deployed and positioned at the ostia of the PVs and a full 8-minute ablation was then performed, while the heart was bathed in a circulating bath of normal saline at 37 degrees. Thermocouples positioned on the endocardial (balloon surface-tissue interface) and epicardial surfaces of the ostia were used to determine whether transmural freezing was achieved. RESULTS: The mean temperatures measured on the endocardial and epicardial tissue in six PV ablations were -38.8 +/- 6.9 degrees C and -10.0 +/- 7.5 degrees C, respectively. The average pulmonary vein thickness was 3.3 +/- 1.4 mm. CONCLUSIONS: A novel cryoablation balloon catheter is capable of achieving transmural freezing of the pulmonary vein. The catheter has promise for future clinical therapy of atrial fibrillation.

Animals↗

Sudden cardiac death in athletes.

The impact of sudden cardiac death (SCD) in athletes has been highlighted by increasing media coverage, as well as medical and lay awareness of the entities associated with SCD. Common etiologies include cardiac abnormalities such as hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD), and coronary artery anomalies, each with varying geographic incidence. New recommendations regarding noninvasive preparticipation screening have emerged in Europe, where the Italian experience of mandatory annual screening of athletes has been the forerunner in efforts to identify individuals at risk. Ongoing clinical efforts are underway to help define the role of implantable cardioverter defibrillators as a preventive measure in appropriate candidates with HCM or ARVD, as well as methods to limit the potential for SCD as a result of chest blows sustained in sports and other recreational activities by means of chest protectors and special sporting equipment for young athletes.

Cardiomyopathy, Hypertrophic↗

Treatment of athletes with cardiac disease or arrhythmias.

Ventricular arrhythmias and sudden cardiac death in the athlete are uncommon but extremely visible because of the high profile of amateur and professional athletes. In athletes under the age of 30 years, the incidence of sudden death is low and in most cases occurs in individuals with inherited heart disease. In the older athlete, sudden death is more common and is generally due to arrhythmias in the context of coronary artery disease. Many athletes with aborted sudden death, arrhythmia-related syncope, or high-risk genetic disorders benefit from therapy with implantable cardioverter-defibrillators (ICDs). Although ICD therapy can effectively abort sudden death, implantation of an ICD generally prohibits an individual from all competitive athletics except low-intensity sports. Recommendations for participation in competitive athletics generally follow the recently published 36th Bethesda Conference Eligibility Recommendations for Competitive Athletes with Cardiovascular Abnormalities.

Journal Article↗

Increased risk of paroxysmal atrial fibrillation episodes associated with acute increases in ambient air pollution.

OBJECTIVES: We reported previously that 24-hr moving average ambient air pollution concentrations were positively associated with ventricular arrhythmias detected by implantable cardioverter defibrillators (ICDs). ICDs also detect paroxysmal atrial fibrillation episodes (PAF) that result in rapid ventricular rates. In this same cohort of ICD patients, we assessed the association between ambient air pollution and episodes of PAF. DESIGN: We performed a case-crossover study. PARTICIPANTS: Patients who lived in the Boston, Massachusetts, metropolitan area and who had ICDs implanted between June 1995 and December 1999 (n=203) were followed until July 2002. EVALUATIONS/MEASUREMENTS: We used conditional logistic regression to explore the association between community air pollution and 91 electrophysiologist-confirmed episodes of PAF among 29 subjects. RESULTS: We found a statistically significant positive association between episodes of PAF and increased ozone concentration (22 ppb) in the hour before the arrhythmia (odds ratio=2.08; 95% confidence interval=1.22, 3.54; p=0.001). The risk estimate for a longer (24-hr) moving average was smaller, thus suggesting an immediate effect. Positive but not statistically significant risks were associated with fine particles, nitrogen dioxide, and black carbon. CONCLUSIONS: Increased ambient O3 pollution was associated with increased risk of episodes of rapid ventricular response due to PAF, thereby suggesting that community air pollution may be a precipitant of these events.

Aged↗

Gender-related differences in the clinical presentation and outcome of hypertrophic cardiomyopathy.

OBJECTIVES: The goal of this study was to assess gender-related differences in a multicenter population with hypertrophic cardiomyopathy (HCM). BACKGROUND: Little is known regarding the impact of gender on the heterogeneous clinical profile and clinical course of HCM. METHODS: We studied 969 consecutive HCM patients from Italy and the U.S. followed over 6.2 +/- 6.1 years. RESULTS: Male patients had a 3:2 predominance (59%), similar in Italy and the U.S. (p = 0.24). At initial evaluation, female patients were older and more symptomatic than male patients (47 +/- 23 years vs. 38 +/- 18 years; p < 0.001; mean New York Heart Association [NYHA] functional class 1.8 +/- 0.8 vs. 1.4 +/- 0.6; p < 0.001), and more frequently showed left ventricular outflow obstruction (37% vs. 23%; p < 0.001). Moreover, female patients were less often diagnosed fortuitously by routine medical examination (23% vs. 41% in male patients, p < 0.001). Female gender was independently associated with the risk of symptom progression to NYHA functional classes III/IV or death from heart failure or stroke compared with male gender (independent relative hazard 1.5; p < 0.001), particularly patients > or =50 years of age and with resting outflow obstruction (p < 0.005). Hypertrophic cardiomyopathy-related mortality and risk of sudden death were similar in men and women. CONCLUSIONS: Women with HCM were under-represented, older, and more symptomatic than men, and showed higher risk of progression to advanced heart failure or death, often associated with outflow obstruction. These gender-specific differences suggest that social, endocrine, or genetic factors may affect the diagnosis and clinical course of HCM. A heightened suspicion for HCM in women may allow for timely implementation of treatment strategies, including relief of obstruction and prevention of sudden death or stroke.

Adult↗

Significance and relation between magnitude of left ventricular hypertrophy and heart failure symptoms in hypertrophic cardiomyopathy.

In hypertrophic cardiomyopathy (HC), an important subgroup of patients develop progressive and disabling symptoms that are related to heart failure and death. Although a direct relation has been demonstrated between left ventricular (LV) wall thickness and likelihood of sudden and unexpected death (usually in patients who are asymptomatic or mildly symptomatic), it is unresolved whether magnitude of hypertrophy is similarly associated with severity of heart failure. To determine the relation of LV wall thickness to heart failure symptoms in HC, 700 consecutive patients who had HC were assessed by 2-dimensional echocardiography. The relation between maximum level of heart failure symptoms by New York Heart Association functional class and maximum LV wall thickness was not linear but rather parabolic. Therefore, marked symptoms were most commonly associated with moderate degrees of LV hypertrophy (wall thickness 16 to 24 mm; 27%) but less frequently with extreme hypertrophy (>/=30 mm 13%) or mild hypertrophy (</=15 mm; 19%, p = 0.0001). Mean New York Heart Association functional class showed a similar pattern with respect to moderate hypertrophy (1.9 +/- 0.8), mild hypertrophy (1.6 +/- 0.9), and extreme hypertrophy (1.6 +/- 0.7, p = 0.005). Multivariable regression analysis showed the parabolic relation between heart failure symptoms and magnitude of LV hypertrophy to be independent of other hypertrophic cardiomyopathy related clinical variables. In conclusion, no direct relation was evident between symptoms of heart failure and magnitude of LV wall thickness, with implications for the natural history of HC.

Adolescent↗