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.

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.

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.

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.