Christopher Madias

Valvular and Structural Heart Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This chapter about antithrombotic therapy for valvular heart disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patient values might lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with rheumatic mitral valve disease complicated singly or in combination by the presence of atrial fibrillation (AF), previous systemic embolism, or left atrial thrombus, we recommend vitamin K antagonist (VKA) therapy (Grade 1A). For patients with rheumatic mitral valve disease and normal sinus rhythm, without left atrial enlargement, we do not suggest antithrombotic therapy unless a separate indication exists (Grade 2C). For patients with mitral valve prolapse (MVP), not complicated by AF, who have not had systemic embolism, unexplained transient ischemic attacks, or ischemic stroke, we recommend against antithrombotic therapy (Grade 1C). In patients with mitral annular calcification complicated by systemic embolism or ischemic stroke, we recommend antiplatelet agent (APA) therapy (Grade 1B). For patients with isolated calcific aortic valve disease, we suggest against antithrombotic therapy (Grade 2C). But, for those with aortic valve disease who have experienced ischemic stroke, we suggest APA therapy (Grade 2C). For patients with stroke associated with aortic atherosclerotic lesions, we recommend low-dose aspirin (ASA) therapy (Grade 1C). For patients with cryptogenic ischemic stroke and a patent foramen ovale (PFO), we recommend APA therapy (Grade 1A). For patients with mechanical heart valves, we recommend VKA therapy (Grade 1A). For patients with mechanical heart valves and history of vascular disease or who have additional risk factors for thromboembolism, we recommend the addition of low-dose aspirin ASA to VKA therapy (Grade 1B). We suggest ASA not be added to long-term VKA therapy in patients with mechanical heart valves who are at particularly high risk of bleeding (Grade 2C). For patients with bioprosthetic heart valves, we recommend ASA (Grade 1B). For patients with bioprosthetic heart valves and additional risk factors for thromboembolism, we recommend VKA therapy (Grade 1C). For patients with infective endocarditis, we recommend against antithrombotic therapy, unless a separate indication exists (Grade 1B).

Parasympathetic response in chick myocytes and mouse heart is controlled by SREBP.

Parasympathetic stimulation of the heart, which provides protection from arrhythmias and sudden death, involves activation of the G protein-coupled inward rectifying K+ channel GIRK1/4 and results in an acetylcholine-sensitive K+ current, I KACh. We describe a unique relationship between lipid homeostasis, the lipid-sensitive transcription factor SREBP-1, regulation of the cardiac parasympathetic response, and the development of ventricular arrhythmia. In embryonic chick atrial myocytes, lipid lowering by culture in lipoprotein-depleted serum increased SREBP-1 levels, GIRK1 expression, and I KACh activation. Regulation of the GIRK1 promoter by SREBP-1 and lipid lowering was dependent on interaction with 2 tandem sterol response elements and an upstream E-box motif. Expression of dominant negative SREBP-1 (DN-SREBP-1) reversed the effect of lipid lowering on I KACh and GIRK1. In SREBP-1 knockout mice, both the response of the heart to parasympathetic stimulation and the expression of GIRK1 were reduced compared with WT. I KACh, attenuated in atrial myocytes from SREBP-1 knockout mice, was stimulated by SREBP-1 expression. Following myocardial infarction, SREBP-1 knockout mice were twice as likely as WT mice to develop ventricular tachycardia in response to programmed ventricular stimulation. These results demonstrate a relationship between lipid metabolism and parasympathetic response that may play a role in arrhythmogenesis.

Acquired long QT syndrome from stress cardiomyopathy is associated with ventricular arrhythmias and torsades de pointes

BACKGROUND Stress cardiomyopathy (SCM) is a syndrome of transient ventricular dysfunction triggered by severe emotional or physical stress, likely resulting from catecholamine-mediated myocardial toxicity. Repolarization abnormalities associated with other hyperadrenergic states can cause QT prolongation and lethal arrhythmia including torsades de pointes (TdP). Despite the development of repolarization abnormalities and QT prolongation in SCM, little is known about the risk of ventricular fibrillation (VF) and TdP. OBJECTIVE The aim of this study was to assess the prevalence and clinical predictors of ventricular arrhythmias in a cohort of patients with SCM. METHODS Data from a registry of consecutive patients with SCM from 2 institutions were reviewed. Patients who developed VF or TdP were identified. Clinical characteristics and outcomes were analyzed and compared with a control group of patients with SCM without VF/TdP. RESULTS Of 93 patients with SCM, 8 (8.6%) experienced VF/TdP. Of these 8 patients, 2 presented with VF and were subsequently diagnosed with SCM. Six other patients experienced pause-dependent TdP or VF after SCM diagnosis in the setting of substantial QT prolongation. Prolongation of the corrected QT interval (QTc) was significantly associated with the occurrence of ventricular arrhythmia (odds ratio 1.28 for each 10 ms increase in QTc, 95% confidence interval 1.10 to 1.50). CONCLUSION SCM can be associated with life-threatening ventricular arrhythmia in over 8% of cases. SCM should be recognized among the causes of acquired long QT syndrome and can be associated with a risk of TdP.

Marked Variability in Susceptibility to Ventricular Fibrillation in an Experimental Commotio Cordis Model

Background— Precordial blows in sports and daily activities can trigger ventricular fibrillation (VF) (commotio cordis). Whereas chest wall blows are common, commotio cordis is rare. Although factors such as timing, location, orientation, and energy of impact are critically important, we also hypothesize that there is individual susceptibility to commotio cordis. Using our model of commotio cordis, we evaluated individual animal susceptibility to VF induction and assessed animal characteristics that might be involved. Methods and Results— This retrospective analysis included 139 juvenile swine (weight, 8 to 54 kg) that were anesthetized and placed prone in a sling to receive chest wall strikes with a ball propelled at 30 to 40 mph. Each animal received a minimum of 4 impacts directly over the cardiac silhouette, all timed to a narrow vulnerable window during cardiac repolarization. Of 1274 total impacts, 360 impacts (28%) resulted in VF. There was wide variability in individual animal susceptibility to VF. In 38 animals, none of the impacts resulted in VF (range, 4 to 18 impacts per animal). The majority of animals (91; 65%) were induced into VF with <30% of the strikes. In fact, only 19 animals (14%) had >50% occurrence of VF with chest wall impacts, and only 7 (5%) had >80% occurrence of chest impacts that induced VF. In the animal-based analysis, individual correlates of VF included animal weight, mean impact velocity, mean left ventricular pressure generated by the blow, mean QRS duration, mean QTc, and QTc variability. In multivariable analysis, mean left ventricular pressure generated by the blow, mean QRS duration, and QTc variability remained significant correlates of risk, and number of impacts gained statistical significance such that animals with more impacts were less susceptible to VF. Conclusions— Swine display a wide range of individual vulnerability to VF triggered by chest wall impact, with a distinct minority being uniquely susceptible. Mild abnormalities in cardiac depolarization and repolarization might underlie this susceptibility. Such individual susceptibility may also be present in humans and contribute to the rarity of commotio cordis.

Role of SREBP-1 in the Development of Parasympathetic Dysfunction in the Hearts of Type 1 Diabetic Akita Mice

Rationale: Diabetic autonomic neuropathy (DAN), a major complication of diabetes mellitus, is characterized, in part, by impaired cardiac parasympathetic responsiveness. Parasympathetic stimulation of the heart involves activation of an acetylcholine-gated K+ current, IKAch, via a (GIRK1)2/(GIRK4)2 K+ channel. Sterol regulatory element binding protein-1 (SREBP-1) is a lipid-sensitive transcription factor. Objective: We describe a unique SREBP-1–dependent mechanism for insulin regulation of cardiac parasympathetic response in a mouse model for DAN. Methods and Results: Using implantable EKG transmitters, we demonstrated that compared with wild-type, Ins2Akita type I diabetic mice demonstrated a decrease in the negative chronotropic response to carbamylcholine characterized by a 2.4-fold decrease in the duration of bradycardia, a 52±8% decrease in atrial expression of GIRK1 (P<0.01), and a 31.3±2.1% decrease in SREBP-1 (P<0.05). Whole-cell patch-clamp studies of atrial myocytes from Akita mice exhibited a markedly decreased carbamylcholine stimulation of IKAch with a peak value of −181±31 pA/pF compared with −451±62 pA/pF (P<0.01) in cells from wild-type mice. Western blot analysis of extracts of Akita mice demonstrated that insulin treatment increased the expression of GIRK1, SREBP-1, and IKAch activity in atrial myocytes from these mice to levels in wild-type mice. Insulin treatment of cultured atrial myocytes stimulated GIRK1 expression 2.68±0.12-fold (P<0.01), which was reversed by overexpression of dominant negative SREBP-1. Finally, adenoviral expression of SREBP-1 in Akita atrial myocytes reversed the impaired IKAch to levels in cells from wild-type mice. Conclusions: These results support a unique molecular mechanism for insulin regulation of GIRK1 expression and parasympathetic response via SREBP-1, which might play a role in the pathogenesis of DAN in response to insulin deficiency in the diabetic heart.

Prevalence and clinical characteristics of right ventricular dysfunction in transient stress cardiomyopathy.

Transient stress cardiomyopathy (TSC) is a cause of reversible left ventricular (LV) dysfunction that is increasingly recognized. Reports to date have focused primarily on LV involvement, with little attention paid to associated right ventricular (RV) dysfunction. With other forms of LV dysfunction, RV involvement has been shown to confer an adverse prognosis. Prevalence, clinical characteristics, and short-term prognosis of RV dysfunction in TSC remain ill-defined. Presenting echocardiograms of 40 patients with TSC were reviewed. RV function was assessed by evaluating regional wall motion and calculating a wall motion score index (WMSI). RV dysfunction was defined as a WMSI >1.0. Clinical and demographic characteristics of patients with and without RV dysfunction were compared. RV dysfunction was identified in 27% of patients (11 of 40). RV WMSI was 1.20 +/- 0.30 for the entire cohort compared with 1.72 +/- 0.30 for those with RV dysfunction (p <0.05). In each case with RV dysfunction, regional wall motion abnormalities involved the apex and spared the base. Patients with RV dysfunction had higher B-type natriuretic peptide levels, higher pulmonary artery systolic pressures, and longer hospital stays. RV dimensions, clinical characteristics, electrocardiographic findings, other biomarkers, and in-hospital complications were similar. In conclusion, RV wall motion abnormalities, predominantly involving the apex and sparing the base, occur in slightly >1/4 of cases of TSC. Although associated with higher B-type natriuretic peptide levels, higher pulmonary artery systolic pressures, and longer hospital stays, RV dysfunction was not associated with significant differences in short-term cardiac morbidity or increased early mortality.

Protecting Our Children From the Consequences of Chest Blows on the Playing Field: A Time for Science Over Marketing

Commotio cordis is the devastating consequence of otherwise innocent-appearing chest-wall blows, with sudden cardiac death often resulting from projectiles striking the precordium.1,2 This phenomenon occurs most commonly in sports when a baseball, lacrosse ball, or hockey puck strikes the chest directly over the cardiac silhouette and triggers ventricular fibrillation.3 During the past several years, the number of documented commotio cordis events reported to our registry has risen to almost 200, more likely a result of enhanced awareness rather than a true increase in incidence. Commotio cordis has now been cited as the second leading cause of sudden death in young athletes4 and is a uniquely pediatric problem, with an average age of only 14 years for the victims (Fig 1). FIGURE 1 Age at which commotio cordis occurred in cases reported to the Commotio Cordis Registry. The median age was 14 years; 90% of case-patients were younger than 21 years. (Reproduced with permission from Maron BJ, Gohman TE, Kyle SB, Estes NAM III, Link MS. JAMA . 2002;287(9):1143.) Among the reported commotio cordis cases, nearly 50% occurred during competitive sports.1,2 Of particular note, some form of chest-wall protection was worn by almost 40% of the athletes who incurred fatal or nonfatal events.5 In these cases, sudden death resulted directly from chest blows as a result of either inadequate chest-barrier composition (ie, with direct precordial impact) or inadequate design (ie, failure to cover the precordium during all bodily movements). In some circumstances, such as with those chest protectors used in lacrosse and baseball, the ball struck the chest barrier … Address correspondence to Mark S. Link, MD, Tufts Medical Center, NEMC Box 197, 750 Washington St, Boston, MA 02111. E-mail: mlink{at}tufts-nemc.org

Usefulness of Transesophageal Echocardiography to Confirm Clinical Utility of CHA2DS2-VASc and CHADS2 Scores in Atrial Flutter

The CHA(2)DS(2)-VASc and CHADS(2) risk stratification schemes are used to predict thromboembolism and ischemic stroke in patients with atrial fibrillation. However, limited data are available regarding the utility of these risk stratification schemes for stroke in patients with atrial flutter. A retrospective analysis of 455 transesophageal echocardiographic studies in patients with atrial flutter was performed to identify left atrial (LA) thrombi and/or spontaneous echocardiographic contrast (SEC). The CHA(2)DS(2)-VASc (Congestive heart failure, Hypertension, Age ≥75 years [doubled risk weight], Diabetes mellitus, previous Stroke/transient ischemic attack [doubled risk weight], Vascular disease, Age 65 to 74 years, Sex) and CHADS(2) (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke/transient ischemic attack [double risk weight]) scores were calculated to stratify the risk of stroke or transient cerebrovascular ischemic events. Transesophageal echocardiography revealed LA thrombi in 5.3% and SEC in 25.9% of patients. Using CHADS(2), LA thrombus was found in 2.2% of the low-intermediate-risk group and 8.3% of the high-risk group (p = 0.005). SEC was found in 19.8% of the low-intermediate-risk group and 32% of the high-risk group (p = 0.004). Using CHA(2)DS(2)-VASc, LA thrombus was found in 1.7% of the low-intermediate-risk group and 6.5% of the high-risk group (p = 0.053). SEC was found in 11.8% of the low-intermediate-risk group versus 30.9% of the high-risk group (p = 0.004). The sensitivity for LA thrombus/SEC with a high CHADS(2) and CHA(2)DS(2)-VASc score was 64.8% and 88.7%, respectively (p = 0.0001). The specificity for LA thrombus/SEC with high CHADS(2) and CHA(2)DS(2)-VASc scores was 52.6% and 28.9%, respectively (p = 0.0001). In conclusion, both CHA(2)DS(2)-VASc and CHADS(2) scores are useful for stroke risk stratification in patients with atrial flutter. CHA(2)DS(2)-VASc had greater sensitivity for LA thrombus and SEC detection at the cost of reduced specificity.

Precordial thump for cardiac arrest is effective for asystole but not for ventricular fibrillation

BACKGROUND Precordial thump for cardiac arrest remains controversial. Although precordial blows can trigger ventricular fibrillation (VF) (i.e., commotio cordis), they paradoxically have been regarded as potential therapy for cardiac arrest. In commotio cordis, impact energy and resultant peak left ventricular (LV) pressure are important variables in VF initiation. OBJECTIVE The purpose of this study was to assess the relationship between LV pressures generated by thumps and their effectiveness in defibrillation of VF or resuscitation of asystole after defibrillation. METHODS After induction of VF, 10 swine each received 18 chest thumps; two sets of three thumps each with a clenched fist, a 30-mph lacrosse ball, and a 40-mph lacrosse ball. If asystole followed defibrillation, manual thumps were given to induce ventricular depolarizations until resumption of spontaneous rhythm. RESULTS During VF, generated LV pressure (mmHg) was 263 +/- 52 with manual thumps, 392 +/- 179 with 30-mph ball thumps, and 616 +/- 182 with 40-mph ball thumps (P <.001). None of the 180 thumps terminated VF. All episodes required electrical defibrillation. During asystole, generated LV pressures were greater for thumps that induced ventricular depolarizations than for those that did not (111 +/- 27 mmHg vs 73 +/- 23 mmHg, P <.001). A significant association was observed between induction of ventricular depolarizations and thump-generated LV pressures (odds ratio 2.0 per 10 mmHg rise in LV pressure, 95% confidence interval 1.8-2.1). CONCLUSION Despite generating high LV pressures, precordial thumps were not effective in terminating VF. Based on these data, precordial thump for VF in cardiac arrest victims cannot be recommended but for asystolic victims might be beneficial.

Reduced diameter spheres increases the risk of chest blow-induced ventricular fibrillation (commotio cordis)

BACKGROUND Sudden death due to low-energy blunt trauma to the precordium (commotio cordis) has been described with a variety of sporting objects. However, the risk of ventricular fibrillation (VF) relative to the shape of the impact object is not known. OBJECTIVE The objective of the current experiment is to test whether the impact object shape is a clinical variable that affects the risk for commotio cordis. METHODS In a juvenile swine model, impacts were given in random order with two different spherical shapes (72 mm diameter, equivalent to a baseball; 42 mm diameter, equivalent to a golf ball) and a flat round object 72 mm in diameter. Objects were equal in weight (150 g), thrown at 30 mph, and gated to the vulnerable portion of the cardiac cycle. RESULTS Sixteen swine received 144 impacts. The flat object did not cause VF (P = .01 compared with the two spherical objects), nonsustained VF, ST elevation, or bundle branch block. The smaller diameter sphere caused VF in nine of 48 impacts (19%), and the larger diameter sphere caused VF in five of 48 impacts (10%; P = .25). The smaller diameter sphere was associated with a greater increase in left ventricular pressure (P <.0001 and P = .001 compared with larger sphere only) and a higher likelihood of ST segment elevations (P <.001 and P = .08 compared with larger sphere only) and bundle branch block (Fishers exact P = .008, and Fishers exact P = .18 compared with larger sphere only). CONCLUSION The shape of the projectile markedly influences the risk of VF from chest wall impact. This effect is likely mediated via a greater increase in left ventricular pressure with smaller diameter objects. Spreading the impact force over a larger area may decrease the risk of sudden death and has implications for the design of protective athletic equipment.