Infants at risk for physical disability may be identified by measures of postural control in supine.

BACKGROUND: Early detection of delay or impairment in motor function is important to guide clinical management and inform prognosis during a critical window for the development of motor control in children. The purpose of this study was to investigate the ability of biomechanical measures of early postural control to distinguish infants with future impairment in motor control from their typically developing peers. METHODS: We recorded postural control from infants lying in supine in several conditions. We compared various center of pressure metrics between infants grouped by birth status (preterm and full term) and by future motor outcome (impaired motor control and typical motor control). RESULTS: One of the seven postural control metrics-path length-was consistently different between groups for both group classifications and for the majority of conditions. CONCLUSIONS: Quantitative measures of early spontaneous infant movement may have promise to distinguish early in life between infants who are at risk for motor impairment or physical disability and those who will demonstrate typical motor control. Our observation that center of pressure path length may be a potential early marker of postural instability and motor control impairment needs further confirmation and further investigation to elucidate the responsible neuromotor mechanisms. IMPACT: The key message of this article is that quantitative measures of infant postural control in supine may have promise to distinguish between infants who will demonstrate future motor impairment and those who will demonstrate typical motor control. One of seven postural control metrics-path length-was consistently different between groups. This metric may be an early marker of postural instability in infants at risk for physical disability.

A Clinical Score for Predicting Atrial Fibrillation in Patients with Cryptogenic Stroke or Transient Ischemic Attack.

OBJECTIVES: Detection of atrial fibrillation (AF) in post-cryptogenic stroke (CS) or transient ischemic attack (TIA) patients carries important therapeutic implications. METHODS: To risk stratify CS/TIA patients for later development of AF, we conducted a retrospective cohort study using data from 1995 to 2015 in the Stanford Translational Research Integrated Database Environment (STRIDE). RESULTS: Of the 9,589 adult patients (age ≥40 years) with CS/TIA included, 482 (5%) patients developed AF post CS/TIA. Of those patients, 28.4, 26.3, and 45.3% were diagnosed with AF 1-12 months, 1-3 years, and >3 years after the index CS/TIA, respectively. Age (≥75 years), obesity, congestive heart failure, hypertension, coronary artery disease, peripheral vascular disease, and valve disease are significant risk factors, with the following respective odds ratios (95% CI): 1.73 (1.39-2.16), 1.53 (1.05-2.18), 3.34 (2.61-4.28), 2.01 (1.53-2.68), 1.72 (1.35-2.19), 1.37 (1.02-1.84), and 2.05 (1.55-2.69). A risk-scoring system, i.e., the HAVOC score, was constructed using these 7 clinical variables that successfully stratify patients into 3 risk groups, with good model discrimination (area under the curve = 0.77). CONCLUSIONS: Findings from this study support the strategy of looking longer and harder for AF in post-CS/TIA patients. The HAVOC score identifies different levels of AF risk and may be used to select patients for extended rhythm monitoring.

Plakoglobin immunolocalization as a diagnostic test for arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: A recent study using an anti-plakoglobin antibody and immunofluorescence methods in endomyocardial tissue specimens found that a marked reduction in plakoglobin staining was highly sensitive and specific for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). The purpose of our study was to determine the diagnostic utility of plakoglobin immunolocalization using more standard immunoperoxidase methods suitable for clinical laboratories. METHODS: Between January 2007 and October 2010, all patients at our center with suspected ARVC underwent noninvasive and genetic testing, right ventricular (RV) angiography, electrophysiologic studies, and endomyocardial biopsy from the RV septum. Several studies using anti-plakoglobin antibodies were performed using standard immunoperoxidase methods at concentrations of 1:50,000 and 1:75,000 after serial dilutions. RESULTS: Among 16 patients, nine patients fulfilled the clinical criteria for ARVC, and seven patients were found to have other cardiac diagnoses. In the initial study (1:50,000) only one of nine ARVC patients showed reduced plakoglobin signal while the others had normal staining. On repeat staining (1:75,000), reduced signal was observed in three of five of the ARVC patients compared to none in controls (four patients did not have adequate tissue for the repeat experiment). CONCLUSION: These results confirm that abnormal plakoglobin staining can differentiate biopsies from patients with ARVC from those with other myopathies, but with low sensitivity. Further, each specimen must be studied at a particular concentration due to variable antibody reactivity. The necessity for such fine-tuning of the reaction, as well as the subjectivity involved in interpretation of the results, would make this method difficult to utilize in routine hospital laboratories.

Association Between Insomnia, Stress Events, and Other Psychosocial Factors and Incident Atrial Fibrillation in Postmenopausal Women: Insights From the Women's Health Initiative.

Background The association between psychosocial factors and atrial fibrillation (AF) is poorly understood. Methods and Results Postmenopausal women from the Women's Health Initiative were retrospectively analyzed to identify incident AF in relation to a panel of validated psychosocial exposure variables, as assessed by multivariable Cox proportional hazard regression and hierarchical cluster analysis. Among the 83 736 women included, the average age was 63.9±7.0 years. Over an average of 10.5±6.2 years follow-up, there were 23 954 cases of incident AF. Hierarchical cluster analysis generated 2 clusters of highly correlated psychosocial variables: the Stress Cluster included stressful life events, depressive symptoms, and insomnia, and the Strain Cluster included optimism, social support, social strain, cynical hostility, and emotional expressiveness. Incident AF was associated with higher values in the Stress Cluster (hazard ratio [HR], 1.07 per unit cluster score [95% CI, 1.05-1.09]) and the Strain Cluster (HR, 1.03 per unit cluster score [95% CI, 1.00-1.05]). Of the 8 individual psychosocial predictors that were tested, insomnia (HR, 1.04 [95% CI, 1.03-1.06]) and stressful life events (HR, 1.02 [95% CI, 1.01-1.04]) were most strongly associated with increased incidence of AF in Cox regression analysis after multivariate adjustment. Subgroup analyses showed that the Strain Cluster was more strongly associated with incident AF in those with lower traditional AF risks (P for interaction=0.02) as determined by the cohorts for heart and aging research in genomic epidemiology for atrial fibrillation score. Conclusions Among postmenopausal women, 2 clusters of psychosocial stressors were found to be significantly associated with incident AF. Further research is needed to validate these associations.

Socioeconomic Burden of Rising Methamphetamine-Associated Heart Failure Hospitalizations in California From 2008 to 2018.

BACKGROUND: Methamphetamine-associated cardiomyopathy/heart failure (MethHF) is an increasingly recognized disease entity in the context of a rising methamphetamine (meth) epidemic that most severely impacts the western United States. Using heart failure (HF) hospitalization data from the Office of Statewide Health Planning and Development, this study aimed to assess trend and disease burden of MethHF in California. METHODS: Adult patients (≥18 years old) with HF as primary hospitalization diagnosis between 2008 and 2018 were included in this study. The association with Meth (MethHF) and those without (non-MethHF) were determined by meth-related International Classification of Diseases-based secondary diagnoses. Statistical significance of trends in age-adjusted rates of hospitalization per 100 000 adults were evaluated using nonparametric analysis. RESULTS: Between 2008 and 2018, 1 033 076 HF hospitalizations were identified: 42 565 were MethHF (4.12%) and 990 511 (95.88%) were non-MethHF. Age-adjusted MethHF hospitalizations per 100 000 increased by 585% from 4.1 in 2008 to 28.1 in 2018, while non-MethHF hospitalizations decreased by 6.0% from 342.3 in 2008 to 321.6 in 2018. The rate of MethHF hospitalization increase more than doubled that of a negative control group with urinary tract infection and meth-related secondary diagnoses (7.82-fold versus 3.48-fold, P<0.001). Annual inflation-adjusted hospitalization charges because of MethHF increased by 840% from $41.5 million in 2008 to $390.2 million in 2018, as compared with an 82% increase for all HF hospitalization from $3.503 billion to $6.376 billion. Patients with MethHF were significantly younger (49.64±10.06 versus 72.20±14.97 years old, P<0.001), predominantly male (79.1% versus 52.4%, P<0.001), with lower Charlson Comorbidity Index, yet they had longer length of stay, more hospitalizations per patient, and more procedures performed during their stays. CONCLUSIONS: MethHF hospitalizations increased sharply during the study period and contributed significantly to the HF hospitalization burden in California. This emerging HF phenotype, which engenders considerable financial and societal costs, calls for an urgent and concerted public health response to contain its spread.

Comparison of Clinical Characteristics and Outcomes of Patients With Reversible Versus Persistent Methamphetamine-Associated Cardiomyopathy.

Anecdotal cases of reversible methamphetamine-associated cardiomyopathy (rMAC) have been reported, but not well understood. This study sought to determine the clinical characteristics, outcomes and predictors of reversibility among patients with rMAC as compared with patients with persistent MAC (pMAC). We retrospectively studied adult MAC patients with left ventricular ejection fraction (LVEF) ≤40% at a single center between 2004 and 2018. rMAC was defined as increase in LVEF by ≥20 points or to ≥50%. Those with persistent LVEF ≤40% constituted the pMAC group. 357 MAC cases were identified: 250 patients had pMAC and 107 had rMAC. After a median follow-up of 45 months (interquartile range 27 to 70), LVEF increased by 28.3 ± 6.9% in rMAC (p <0.001), whereas it was unchanged in pMAC (Δ: -0.5 ± 8.7%, p = 0.350). Heart failure hospitalizations and New York Heart Association Class III/IV heart failure were both significantly reduced for rMAC than the pMAC group. All-cause mortality was 21.6% overall, 28% in pMAC and 6.5% in the rMAC group (p <0.001). Kaplan-Meier survival curves demonstrated significantly higher cumulative survival for rMAC (Log Rank p <0.001). Multivariable logistic regression identified MA cessation (odds ratio/OR: 4.23, 95% confidence interval/CI: 2.47 to 7.38, p <0.001) and baseline right ventricular end systolic area (OR: 0.92, 95% CI: 0.87 to 0.97, p = 0.001) as strongly predictive of MAC reversal. In conclusion, MAC reversal is not uncommon and is associated with significant clinical improvement including reduced mortality. It can be facilitated by MA cessation when the cardiac chambers, especially the right ventricle, are not severely dilated.

Evaluation of a clinical score for predicting atrial fibrillation in cryptogenic stroke patients with insertable cardiac monitors: results from the CRYSTAL AF study.

BACKGROUND: The HAVOC score was previously developed to predict the risk of atrial fibrillation (AF) after cryptogenic stroke (CS) or transient ischemic attack (TIA). The purpose of this study was to apply the HAVOC score to patients who received insertable cardiac monitors (ICMs) in the CRYSTAL AF study. METHODS: All patients from the CRYSTAL AF study who received an ICM were included. HAVOC score (one point each for peripheral vascular disease and obesity with body mass index >30, two points each for hypertension, age ⩾ 75, valvular heart disease, and coronary artery disease, 4 points for congestive heart failure) was computed for all patients. The primary endpoint was AF detection by 12 months of ICM monitoring. RESULTS: A total of 214 patients who received ICM were included. AF was detected in 40 patients while the remaining 174 patients were AF negative. The HAVOC score was significantly higher among patients with AF [median 3.0 with interquartile range (IQR) 2-4] than those without AF [median 2.0 (IQR 0-3)], p = 0.01. AF increased significantly across the three HAVOC score groups: 11% in Group A (score 0-1), 18% in Group B (score 2-3), and 32 % in Group C (score ⩾ 4) with p = 0.02. CONCLUSIONS: The HAVOC score was shown in this post hoc analysis of CRYSTAL AF to successfully stratify AF risk post CS or TIA. The 11% AF rate in the lowest HAVOC score group highlights the significance of nontraditional contributors to AF and ischemic stroke.

Clinical Characteristics and Outcome of Methamphetamine-Associated Pulmonary Arterial Hypertension and Dilated Cardiomyopathy.

OBJECTIVES: This study sought to characterize patients with methamphetamine-associated pulmonary arterial hypertension (MA-PAH) and cardiomyopathy (MA-CMP), to compare with MA controls (MA-CTL), users with structurally normal hearts, with the aim of identifying risk factors for these conditions. BACKGROUND: MA-PAH and MA-CMP are 2 poorly understood cardiac complications in MA users. METHODS: We retrospectively studied the clinical characteristics and outcomes of 50 MA-PAH, 296 MA-CMP, and 356 MA-CTL patients, whom we evaluated between 2010 and 2017. RESULTS: After a median follow-up of 20.0 months (interquartile range [IQR]: 7.6 to 42.6 months), all-cause mortality was 18.0% for MA-PAH, 15.2% for MA-CMP, and 4.5% for MA-CTL group (p < 0.001). More women (58%) were in the MA-PAH group than in the MA-CMP (14%; p < 0.001) and MA-CTL (42%; p = 0.028) groups, whereas the MA-CMP group was predominantly male (86% vs. 58% in the MA-CTL group; p < 0.001). More MA-CMP patients had hypertension (p < 0.001) or alcoholism (p < 0.001) than MA-CTL patients. Logistic regression analyses identified male sex, alcoholism, and hypertension as independent factors associated with MA-CMP with the following respective adjusted odds ratios (OR) of 3.791 (95% confidence interval [CI]: 2.508 to 5.730), OR of 2.959 (95% CI: 2.084 to 4.203), and OR of 2.111 (95% CI: 1.486 to 2.999), whereas female sex was the only factor associated with MA-PAH. CONCLUSIONS: Both MA-PAH and MA-CMP patients carried significant disease burden and mortality risk. Male sex, hypertension, and alcoholism were strongly associated with MA-CMP, whereas female sex and other unknown factors may influence development of MA-PAH. This study adds to the understanding of MA-associated cardiac complications and highlights directions for future investigation.

Cardiac MRI T2* in Liver Transplant Candidates: Application and Performance of a Novel Imaging Technique to Identify Patients at Risk for Poor Posttransplant Cardiac Outcomes.

BACKGROUND: In end-stage liver disease, alterations in iron metabolism can lead to iron overload and development of iron overload cardiomyopathy. In liver transplant candidates, evaluation for cardiac iron overload and dysfunction can help to identify candidates at increased risk for peritransplant morbidity and mortality, though recommendations for pretransplant evaluation of cardiac iron overload are not standardized. Cardiac Magnetic Resonance Imaging T2* (CMRI-T2*) is a validated method to quantify cardiac iron deposition, with normal T2* value of 20 ms or greater. In this study, we sought to identify the incidence and predictors of iron overload by CMRI-T2* and to evaluate the impact of cardiac and iron overload on morbidity and mortality after liver transplantation. METHODS: In this retrospective single-center cohort study, all liver transplant candidates who underwent a pretransplant CMRI-T2* between January 1, 2008, and June 30, 2016, were included to analyze the association between clinical characteristics and low T2* using logistic regression. RESULTS: One hundred seventy-nine liver transplant candidates who received CMRI-T2* were included. Median age was 57 years, 73.2% were male, and 47.6% were white. 49.7% had hepatitis C and 2.8% had hemochromatosis. Median Model for End-Stage Liver Disease score was 25. 65.2% were Child-Pugh C. In multivariable logistic regression, T2* less than 20 ms (n = 35) was associated with Model for End-Stage Liver Disease score of 25 or greater (odds ratio [OR], 3.65; P = 0.007), Child-Pugh C (OR, 3.42; P = 0.03), and echocardiographic systolic ejection fraction less than 65% (OR, 2.24; P = 0.01). Posttransplant heart failure occurred exclusively in recipients with T2* less than 15 ms. Survival was worse in T2* 10 to 14.9 versus T2* of 20 ms or greater (hazard ratio, 3.85; P = 0.003), but not for 15 to 19.9 versus T2* of 20 ms or greater. CONCLUSIONS: Severity of liver disease and systolic dysfunction is associated with T2* less than 20 ms, though there was no difference in posttransplant outcomes between T2* 15 to 19.9 and T2* 20 ms or greater, suggesting that individuals with T2* of 15 ms or greater may be suitable transplant candidates. CMRI-T2* is an additional diagnostic tool in evaluating transplant candidates at high risk for posttransplant cardiac complications.

Frequency and Associated Clinical Features of Functional Tricuspid Regurgitation in Patients With Chronic Atrial Fibrillation.

Significant functional tricuspid regurgitation (TR) can develop in some but not all patients with chronic atrial fibrillation (AF). This study sought to identify factors likely to be involved in determining the severity of TR in patients with chronic AF. In this retrospective cohort study of adult patients referred for transthoracic echocardiography for evaluation of AF between 2004 and 2015, we identified 170 patients with chronic AF in the absence of structural or known coronary heart disease. Patients were classified into nonsevere (89 patients) versus severe TR (81 patients) groups based on a comprehensive assessment of color Doppler, spectral Doppler, and morphologic parameters of the tricuspid valve and right side of the heart. Patients with severe TR were significantly older (76 ± 10 vs 70 ± 11, p <0.001), with smaller body surface area (1.7 ± 0.3 m2 vs 1.9 ± 0.23 m2, p = 0.001) and with female predominance (percentage of men 30% vs 57%, p <0.001). Although comorbidities, use of cardiovascular medications, and left-sided cardiac parameters were statistically indistinguishable between these 2 groups, right-sided cardiac dimensions, tricuspid valve tethering height, and tricuspid valve tethering area were significantly larger in the severe TR group. A comprehensive multivariate logistic regression model (model 1) identified the age, gender, right ventricular systolic pressure, right atrial volume index, and right ventricular end-diastolic area as independent factors associated with TR severity. A simplified logistic regression model using only clinical factors (model 2) confirmed the age, gender, and right ventricular systolic pressure as clinically relevant factors in relation to TR.

Oxygen-Generating Biomaterials: A New, Viable Paradigm for Tissue Engineering?

There have been many attempts to provide sufficient nutrients, especially oxygen, to engineered large tissues to overcome the effects of hypoxia or poor vascularization. Delivering sufficient oxygen to the transplanted cells is one of the most critical issues that affects cell survival and correct maturation of engineered tissues. An emerging approach is using 3D scaffolds made from oxygen-generating biomaterials to tackle transport limitations deep within the engineered tissues. This class of biomaterials has opened a new window for overcoming the challenges associated with ischemia occurring within large tissue constructs. This review critically assesses oxygen-generating reagents, the main approaches for developing oxygen-generating biomaterials, and their potential as 3D scaffolds for regenerative medicine in a clinical setting.

Potent antifibrillatory effects of intrapericardial nitroglycerin in the ischemic porcine heart.

OBJECTIVES: We investigated the antiarrhythmic effects of intrapericardial nitroglycerin (NTG) during acute myocardial ischemia in the porcine heart. BACKGROUND: Nitroglycerin is a nitric oxide donor that exerts potent effects on the cardiovascular system. Intrapericardial administration allows investigation of pharmacologic actions on cardiac tissue in an in vivo system while minimizing the confounding influences of systemic effects. METHODS: In 29 closed-chest pigs, myocardial ischemia was induced by intraluminal balloon occlusion of the left anterior descending coronary artery. Arrhythmia incidence was monitored during 5-min balloon inflations performed without drug and at 15, 45, 75, and 105 min after NTG (4,000 microg bolus) administered by percutaneous transatrial access into the pericardial space. Electrocardiograms were monitored for ischemia-induced T-wave alternans (TWA), a marker of electrical instability. The antiadrenergic potential of NTG was investigated by examining the drug's suppression of dobutamine-induced increase in myocardial contractility. RESULTS: Control coronary artery occlusion provoked ventricular fibrillation (VF) in all animals. Intrapericardial NTG suppressed VF at 45 min in all six pigs (p < 0.05) and reduced TWA across a parallel time course (from 459.1 +/- 144.4 microV before drug to 42.22 +/- 13.96 microV at 45 min, p = 0.047). The antifibrillatory effect occurred as early as 15 min and persisted for up to 75 min. Augmentation of maximum of the first time derivative of left ventricular pressure by dobutamine was blunted by intrapericardial NTG (from 3,999 +/- 196 mm Hg/s before NTG to 3,543 +/- 220 mm Hg/s at 15 min, p = 0.012). CONCLUSIONS: Intrapericardial NTG exerts a robust antifibrillatory action. Potential mechanisms include reduction in electrical instability and blunting of adrenergic effects.

Morphology impact on oxygen sensing ability of Ru(dpp)3Cl2 containing biocompatible polymers.

Especially for tissue engineering applications, the diffusion of oxygen is a critical factor affecting spatial distribution and migration of cells. The cellular oxygen demand also fluctuates depending on tissue type and growth phase. Sensors that determine dissolved oxygen levels under biological conditions provide critical metabolic information about the growing cells as well as the state of the tissue culture within the tissue scaffold. This work focused on the effect of the scaffold morphology on the oxygen sensing response time. It was found that electrospun scaffolds had a faster oxygen-sensing response time than their bulk film counterparts. Tris-(4,7-diphenyl-1,10-phenanthroline) ruthenium (II) dichloride doped electrospun fiber mats of polycaprolactone (PCL) were found to be the most responsive to the presence of oxygen, followed by polyethylene (PEO) glycol mats. Systems containing poly vinyl alcohol were found to be the least responsive. This would suggest that, out of all the polymers tested, PCL and PEO are the most suitable biomaterials for oxygen-sensing applications.

Comparison of radionuclide angiographic synchrony analysis to echocardiography and magnetic resonance imaging for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable arrhythmia syndrome entailing a high risk of sudden cardiac death. Discernment from benign arrhythmia disorders, particularly right ventricular outflow tract ventricular tachycardia (RVOT VT), may be challenging, providing an impetus to explore alternative modalities that may facilitate evaluation of patients with suspected ARVC. OBJECTIVE: We evaluated the role of equilibrium radionuclide angiography (ERNA) as a diagnostic tool for ARVC. METHODS: ERNA measures of ventricular synchrony-synchrony (S) and entropy (E)-were examined in patients with ARVC (n = 16), those with RVOT VT (n = 13), and healthy controls (n = 49). The sensitivity and specificity of ERNA parameters for ARVC diagnosis were compared with those of echocardiography (ECHO) and cardiovascular magnetic resonance (CMR). RESULTS: ERNA right ventricular synchrony parameters in patients with ARVC (S = 0.91 ± 0.07; E = 0.61 ± 0.1) differed significantly from those in patients with RVOT VT (S = 0.99 ± 0.01 [P = .0015]; E = 0.46 ± 0.05 [P < .001]) and healthy controls (S = 0.97 ± 0.02 [P = .003]; E = 0.48 ± 0.07 [P = .001]). The sensitivity of ERNA synchrony parameters for ARVC diagnosis (81%) was higher than that for ECHO (38%; P = .033) and similar to that for CMR (69%; P = .162), while specificity was lower for ERNA (89%) than that for ECHO and CMR (both 100%; P = .008). CONCLUSION: ERNA right ventricular synchrony parameters can distinguish patients with ARVC from controls with structurally normal hearts, and its performance is comparable to that of ECHO and CMR for ARVC diagnosis. These findings suggest that ERNA may serve as a valuable imaging tool in the diagnostic evaluation of patients with suspected ARVC.

Suppression of calcium-induced repolarization heterogeneity as a mechanism of nitroglycerin's antiarrhythmic action.

This study examined whether the antifibrillatory action of nitroglycerin (NTG) is attributable to reduction in calcium-induced heterogeneity of repolarization independent of autonomic and coronary vasodilatory influences. The effects of intrapericardial (IPC) NTG on coronary blood flow, contractility, repolarization, and arrhythmia susceptibility were measured in anesthetized pigs (N = 43). Autonomic influences were minimized by vagotomy and beta-adrenergic blockade (metoprolol, 1.25 mg/kg, intravenous). Electrophysiological parameters were tested at 30 min, a time when coronary hemodynamics had returned to baseline. Intracoronary calcium chloride (CaCl2, 50-mg bolus) injection augmented contractility (dP/dt(max), 1760 +/- 144 to 2769 +/- 274 mmHg/s, and following NTG, 1531 +/- 384 to 2138 +/- 242 mmHg/s, P < 0.0002), reflecting increased myocardial intracellular calcium. Calcium increased repolarization heterogeneity (interlead precordial T-wave heterogeneity, 95 +/- 15 to 264 +/- 33 microV, P < 0.006; T(peak)-T(end), an index of transmural dispersion of repolarization, 37 +/- 3 to 76 +/- 6 ms, P < 0.05) and lowered repetitive extrasystole threshold (RET; 24 +/- 2 to 13 +/- 1 mA, and following NTG, 32 +/- 4 to 18 +/- 1 mA, P < 0.0001). IPC NTG raised the RET from baseline by 33% and blunted calcium-induced contractility (dP/dt(max) by 23%, P < 0.05), repolarization changes (T-wave heterogeneity by 24%, P < 0.006; T(peak)-T(end) by 18%, P = 0.04), and arrhythmia vulnerability (RET by 39%, P < 0.003). Thus, the capacity of NTG to suppress calcium-induced repolarization heterogeneity is an important mechanism of its antiarrhythmic action, which is independent of autonomic and vasodilatory actions.