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.

The association of abnormal findings on transthoracic echocardiography with 2011 Appropriate Use Criteria and clinical impact.

Transthoracic echocardiography (TTE) Appropriate Use Criteria (AUC) were developed to promote high-value care. We describe the prevalence of clinically significant abnormal TTE findings overall and in subgroups defined by appropriate and inappropriate AUC, and their association with clinical impact. 548 consecutive TTEs at an academic medical center were retrospectively reviewed for AUC, clinical impact, and TTE abnormalities. TTE reports within 1 year of the index TTE were reviewed to determine if abnormalities were new, unchanged, or resolved. Clinical impact was classified into no change, active change, or continuation of care. 91% of TTEs were appropriate, 5% were inappropriate, and 4% were uncertain by AUC. 46% of all TTEs and 57% of first-time TTEs had no significant TTE abnormalities. Appropriate TTEs had a higher prevalence of ≥1 TTE abnormality than inappropriate TTEs (56 vs. 33%, p = 0.029). Among repeat TTEs, 72 % had ≥1 TTE abnormality, however only 25% had a new abnormality. The prevalence of a new abnormality was similar between inappropriate and appropriate repeat TTEs (25 vs. 26%, p = 1.0). The prevalence of ≥1 abnormality was similar between TTEs that resulted in active change and no change in care (70 vs. 64%, p = 0.06). Although most TTEs were appropriate as defined by AUC, the majority had no significant abnormalities. Although most TTEs were appropriate by AUC, >50% of all TTEs and 25% of repeat TTEs had no significant abnormalities. Appropriate TTEs had a higher prevalence of abnormalities, however the prevalence of abnormalities was similar between TTEs that resulted in active change versus no change in care.

Appropriate use and clinical impact of transthoracic echocardiography.

IMPORTANCE: Transthoracic echocardiography (TTE) accounts for almost half of all cardiac imaging services and is a widely available and versatile tool. Appropriate use criteria (AUC) for echocardiography were developed to improve patient care and health outcomes. Prior studies have shown that most TTEs are appropriate by AUC. However, the associations among TTE, AUC, and their clinical impact have not been well explored. OBJECTIVES: To describe the proportion of TTEs that affect clinical care in an academic medical center overall and in subgroups defined as appropriate and inappropriate by AUC. DESIGN AND SETTING: Retrospective review of medical records from 535 consecutive TTEs at an academic medical center was performed. The TTEs were classified according to 2011 AUC by 2 cardiologists blinded to clinical impact and were assessed for clinical impact by 2 cardiologists blinded to AUC. Clinical impact was assigned to 1 of the following 3 categories: (1) active change in care, (2) continuation of current care, or (3) no change in care. PARTICIPANTS: Five hundred thirty-five patients undergoing TTE. EXPOSURE: Transthoracic echocardiography. MAIN OUTCOMES AND MEASURES Prevalence of appropriate, inappropriate, and uncertain TTEs and prevalence of clinical impact subcategories. RESULTS: Overall, 31.8% of TTEs resulted in an active change in care; 46.9%, continuation of current care; and 21.3%, no change in care. By 2011 AUC, 91.8% of TTEs were appropriate; 4.3%, inappropriate; and 3.9%, uncertain. We detected no statistically significant difference between appropriate and inappropriate TTEs in the proportion of TTEs that led to active change in care (32.2% vs 21.7%; P= .29). CONCLUSIONS AND RELEVANCE: Although 9 in 10 TTEs were appropriate by 2011 AUC, fewer than 1 in 3 TTEs resulted in an active change in care, nearly half resulted in continuation of current care, and slightly more than 1 in 5 resulted in no change in care. The low rate of active change in care (31.8%) among TTEs mostly classified as appropriate (91.8%) highlights the need for a better method to optimize TTE utilization to use limited health care resources efficiently while providing high-quality care.

Effect of 9p21.3 coronary artery disease locus neighboring genes on atherosclerosis in mice.

BACKGROUND: The human 9p21.3 chromosome locus has been shown to be an independent risk factor for atherosclerosis in multiple large-scale genome-wide association studies, but the underlying mechanism remains unknown. We set out to investigate the potential role of the 9p21.3 locus neighboring genes, including Mtap, the 2 isoforms of Cdkn2a, p16Ink4a and p19Arf, and Cdkn2b, in atherosclerosis using knockout mice models. METHODS AND RESULTS: Gene-targeted mice for neighboring genes, including Mtap, Cdkn2a, p19Arf, and Cdkn2b, were each bred to mice carrying the human APO*E3 Leiden transgene that sensitizes the mice for atherosclerotic lesions through elevated plasma cholesterol. We found that the mice heterozygous for Mtap developed larger lesions compared with wild-type mice (49623±21650 versus 18899±9604 µm(2) per section [mean±SD]; P=0.01), with morphology similar to that of wild-type mice. The Mtap heterozygous mice demonstrated changes in metabolic and methylation profiles and CD4(+) cell counts. The Cdkn2a knockout mice had smaller lesions compared with wild-type and heterozygous mice, and there were no significant differences in lesion size in p19Arf and Cdkn2b mutants compared with wild type. We observed extensive, tissue-specific compensatory regulation of the Cdkn2a and Cdkn2b genes among the various knockout mice, making the effects on atherosclerosis difficult to interpret. CONCLUSIONS: Mtap plays a protective role against atherosclerosis, whereas Cdkn2a appears to be modestly proatherogenic. However, no relation was found between the 9p21 genotype and the transcription of 9p21 neighboring genes in primary human aortic vascular cells in vitro. There is extensive compensatory regulation in the highly conserved 9p21 orthologous region in mice.

Cardiac paraganglioma: diagnostic and surgical challenges.

Primary cardiac paragangliomas are rare extra-adrenal tumors. Though they account for less than 1% of all primary cardiac tumors, they are considerable sources of morbidity and mortality. In this case review, we discuss the challenges associated with the diagnosis and management of cardiac paragangliomas.

Understanding atherosclerosis through mouse genetics.

During the past year studies with mouse models have significantly clarified our understanding of atherosclerosis. Noteworthy achievements include: the discovery of a number of novel genes and pathways; new evidence emphasizing the role of lymphocytes in atherogenesis; the development of mouse models exhibiting advanced lesions with evidence of thrombosis; and new results indicating an anti-atherogenic effect of testosterone.