Effect of modernized collaborative care for depression on depressive symptoms and cardiovascular disease risk biomarkers: eIMPACT randomized controlled trial.

Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our objective was to determine whether successful depression treatment before, versus after, clinical CVD onset reduces CVD risk in depression. We conducted a single-center, parallel-group, assessor-blinded randomized controlled trial. Primary care patients with depression and elevated CVD risk from a safety net healthcare system (N = 216, Mage = 59 years, 78% female, 50% Black, 46% with income <$10,000/year) were randomized to 12 months of the eIMPACT intervention (modernized collaborative care involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and psychiatrists). Outcomes were depressive symptoms and CVD risk biomarkers at 12 months. Intervention participants, versus usual care participants, exhibited moderate-to-large (Hedges' g = -0.65, p < 0.01) improvements in depressive symptoms. Clinical response data yielded similar results - 43% of intervention participants, versus 17% of usual care participants, had a ≥ 50% reduction in depressive symptoms (OR = 3.73, 95% CI: 1.93-7.21, p < 0.01). However, no treatment group differences were observed for the CVD risk biomarkers - i.e., brachial flow-mediated dilation, high-frequency heart rate variability, interleukin-6, high-sensitivity C-reactive protein, ß-thromboglobulin, and platelet factor 4 (Hedges' gs = -0.23 to 0.02, ps ≥ 0.09). Our modernized collaborative care intervention - which harnessed technology to maximize access and minimize resources - produced clinically meaningful improvements in depressive symptoms. However, successful depression treatment did not lower CVD risk biomarkers. Our findings indicate that depression treatment alone may not be sufficient to reduce the excess CVD risk of people with depression and that alternative approaches are needed. In addition, our effective intervention highlights the utility of eHealth interventions and centralized, remote treatment delivery in safety net clinical settings and could inform contemporary integrated care approaches. Trial Registration:ClinicalTrials.gov Identifier: NCT02458690.

Measures of social deprivation and outcomes after percutaneous coronary intervention.

BACKGROUND: Disparities in socioeconomic status are a frequently cited factor associated with worse cardiovascular outcomes. The social deprivation index (SDI) can be used to quantify socioeconomic resources at the population level. OBJECTIVES: The aim of this study was to assess the association of SDI with clinical outcomes following percutaneous coronary interventions (PCI). METHODS: This was a retrospective observational analysis of patients who underwent PCI and were included in a multicenter cardiac catheterization registry study. Baseline characteristics, congestive heart failure (CHF) readmission rates and survival were compared between patients with the highest and lower SDI. SDI was calculated based on the US community survey census tract-level data. RESULTS: Patients within the highest SDI quintile (n = 1843) had more comorbidities and a higher risk of death [hazard ratio (HR): 1.22 (95% confidence interval, CI: 1.1-1.39, p = 0.004); log rank: p = 0.009] and CHF readmission [HR: 1.56 (1.39-1.75, p < 0.001); log rank: p < 0.001) as compared with those in the lower quintiles (n = 10,201) during mean follow-up of 3 years. Increased risk of highest SDI for all-cause mortality and CHF remained significant after adjustment in multivariable analysis for factors associated with highest SDI. CONCLUSIONS: Patients within the highest SDI quintile had a greater proportion of comorbidities as well as higher risk for adverse outcomes as compared with patients with a lower SDI following PCI.

Social deprivation index and ischemic events after percutaneous coronary intervention in patients with diabetes mellitus.

The aim of this study was to assess neighborhood-based differences in outcomes of diabetics versus non-diabetics undergoing percutaneous coronary interventions. Disparities in healthcare access impact long-term outcomes in safety net populations. Diabetes mellitus (DM) is associated with worse clinical outcomes in patients with coronary artery disease (CAD) and may disproportionately impact patients with CAD from underserved populations. We created a geocoded retrospective cohort of patients who underwent percutaneous coronary intervention (PCI) at an urban safety net hospital in this single-center cohort analysis. We evaluated long-term ischemic events in diabetics versus nondiabetics through review of electronic medical records. Social deprivation index (SDI) was calculated based on US-census tract level and stratified according to quintiles. Among 1002 patients, 46% (n = 463) were diabetic and among those 48% (n = 222) were in the highest quintile of SDI. Baseline and angiographic characteristics were similar among diabetic and nondiabetic subjects. Among diabetic patients, those in the highest SDI quintile had significantly higher risk of cardiovascular death and myocardial infarction as compared to those in the remaining quintiles (log rank: p = 0.029) (adjusted hazard's ratio: 1.72 [95% CI: 1.01-2.92], p = 0.04). There was no association of the SDI with outcomes in nondiabetic patients (log rank: p = 0.39). In an underserved population, patients with diabetes and high SDI demonstrate higher rates of adverse ischemic events and cardiovascular death during long-term follow up after PCI. Further research examining the impact of disparities in healthcare access on outcomes after PCI in patients with diabetes is warranted.

Enhanced Response to Drug-Induced QT Interval Lengthening in Patients with Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Patients with heart failure (HF) with reduced ejection fraction demonstrate enhanced response to drug-induced QT interval lengthening and are at increased risk for torsades de pointes. The influence of HF with preserved ejection fraction (HFpEF) on response to drug-induced QT lengthening is unknown. METHODS AND RESULTS: We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched control subjects without HF. Serial 12-lead electrocardiograms were obtained for determination of QT intervals. Demographics, maximum serum ibutilide concentrations, area under the serum ibutilide concentration vs time curves, and baseline Fridericia-corrected QT (QTF) (417 ± 14 vs 413 ± 15 ms, P = .54) were similar in the HFpEF and control groups. Area under the effect (QTFvs time) curve (AUEC) from 0 to 1.17 hours during and following the ibutilide infusion was greater in the HFpEF group (519 ± 19 vs 497 ± 18 ms·h, P= .04), as was AUEC from 0 to 8.17 hours (3576 ± 125 vs 3428 ± 161 ms·h, P = .03) indicating greater QTF interval exposure. Maximum QTF (454 ± 15 vs 443 ± 22 ms, P = .18) and maximum percent increase in QTF from baseline (8.2 ± 2.1 vs 6.7 ± 1.9%, P = .10) in the 2 groups were not significantly different. CONCLUSIONS: HFpEF is associated with enhanced response to drug-induced QT interval lengthening.

Progesterone pretreatment reduces the incidence of drug-induced torsades de pointes in atrioventricular node-ablated isolated perfused rabbit hearts.

INTRODUCTION: Higher progesterone concentrations are protective against drug-induced prolongation of ventricular repolarization. We tested the hypothesis that pretreatment with progesterone reduces the incidence of drug-induced torsades de pointes (TdP). METHODS AND RESULTS: Female New Zealand white rabbits (2.5-3.2 kg) underwent ovariectomy and were randomized to undergo implantation with subcutaneous 21-day sustained release pellets containing progesterone 50 mg (n = 22) or placebo (n = 23). After 20 days, hearts were excised, mounted, and perfused with modified Krebs-Henseleit solution. The atrioventricular (AV) node was destroyed manually. Following a 15-minute equilibration period, hearts were perfused with dofetilide 100 nM for 30 minutes, during which the electrocardiogram was recorded continuously. Incidences of spontaneous TdP, other ventricular arrhythmias and mean QTc intervals were compared. Median serum progesterone concentrations were higher in progesterone vs placebo-treated rabbits (3.8 [range, 2.8-5.1] vs 0.7 [0.4-1.7] ng/mL, P < 0.0001). Median serum estradiol concentrations were similar (58 [22-72] vs 53 [34-62] pg/mL), P = 0.79). The incidence of TdP was lower in hearts from progesterone-treated rabbits (27% vs 61%, P = 0.049). The incidences of bigeminy (36% vs 74%, P = 0.03) and trigeminy (18% vs 57%, P = 0.01) were also lower in hearts from progesterone-treated rabbits. There was no significant difference between groups in incidence of couplets (59% vs 74%, P = 0.54) or monomorphic ventricular tachycardia (14% vs 30%, P = 0.28). Maximum QT c interval and short-term beat-to-beat QT interval variability during dofetilide perfusion were significantly shorter in hearts from progesterone-treated rabbits. CONCLUSIONS: Pretreatment with progesterone reduces the incidence of drug-induced TdP, bigeminy, and trigeminy in isolated perfused AV node-ablated rabbit hearts.

Ondansetron blocks wild-type and p.F503L variant small-conductance Ca2+-activated K+ channels.

Apamin-sensitive small-conductance Ca2+-activated K+ (SK) current ( IKAS) is encoded by Ca2+-activated K+ channel subfamily N ( KCNN) genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT syndrome (diLQTS), we screened for KCNN variants among patients with diLQTS, determined the properties of heterologously expressed wild-type (WT) and variant KCNN channels, and determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS. We searched 2,306,335 records in the Indiana Network for Patient Care and found 11 patients with diLQTS who had DNA available in the Indiana Biobank. DNA sequencing discovered a heterozygous KCNN2 variant (p.F503L) in a 52-yr-old woman presenting with corrected QT interval prolongation at baseline (473 ms) and further corrected QT interval lengthening (601 ms) after oral administration of ondansetron. That patient was also heterozygous for the p.S38G and p.P2835S variants of the QT-controlling genes KCNE1 and ankyrin 2, respectively. Patch-clamp experiments revealed that the p.F503L KCNN2 variant heterologously expressed in human embryonic kidney (HEK)-293 cells augmented Ca2+ sensitivity, increasing IKAS density. The fraction of total F503L-KCNN2 protein retained in the membrane was higher than that of WT KCNN2 protein. Ondansetron at nanomolar concentrations inhibited WT and p.F503L SK2 channels expressed in HEK-293 cells as well as native SK channels in ventricular cardiomyocytes. Ondansetron-induced IKAS inhibition was also demonstrated in Langendorff-perfused murine hearts. In conclusion, the heterozygous p.F503L KCNN2 variant increases Ca2+ sensitivity and IKAS density in transfected HEK-293 cells. Ondansetron at therapeutic (i.e., nanomolar) concentrations is a potent IKAS blocker. NEW & NOTEWORTHY We showed that ondansetron, a 5-HT3 receptor antagonist, blocks small-conductance Ca2+-activated K+ (SK) current. Ondansetron may be useful in controlling arrhythmias in which increased SK current is a likely contributor. However, its SK-blocking effects may also facilitate the development of drug-induced long QT syndrome.

Surgery for Aortic Dilatation in Patients With Bicuspid Aortic Valves: A Statement of Clarification From the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: the "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease" (Circulation. 2010;121:e266-e369) and the "2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease" (Circulation. 2014;129:e521-e643). However, the 2 guidelines differ with regard to the recommended threshold of aortic root or ascending aortic dilatation that would justify surgical intervention in patients with bicuspid aortic valves. The ACC and AHA therefore convened a subcommittee representing members of the 2 guideline writing committees to review the evidence, reach consensus, and draft a statement of clarification for both guidelines. This statement of clarification uses the ACC/AHA revised structure for delineating the Class of Recommendation and Level of Evidence to provide recommendations that replace those contained in Section 9.2.2.1 of the thoracic aortic disease guideline and Section 5.1.3 of the valvular heart disease guideline.

Influence of Zoledronic Acid on Atrial Electrophysiological Parameters and Electrocardiographic Measurements.

INTRODUCTION: Our objective was to determine effects of zoledronic acid (ZA) on atrial electrophysiological parameters and electrocardiographic measurements. METHODS AND RESULTS: Ex vivo perfusion study: Isolated guinea pig hearts were perfused with modified Krebs-Henseleit (K-H) buffer with or without ZA 0.07 mg/kg/L (each n = 6). In ZA-perfused hearts, atrial action potential at 90% repolarization (APD90 ) decreased more from baseline than in controls (-23.2% ± -5.1% vs. -2.1% ± -8.1%, P < 0 .0001), as did APD30 (-28.8% ± -3.8% vs. -2.1% ± -2.1%, P < 0.0001). In vivo dose-response study: Guinea pigs underwent intraperitoneal injections every 2 weeks in 1 of 4 groups (each n = 8): ZA 0.007 mg/kg (low-dose), ZA 0.07 mg/kg (medium-dose), ZA 0.7 mg/kg (high-dose), or placebo. Hearts were excised at 8 weeks and perfused with modified K-H. Atrial effective refractory period (ERP) was lower with medium- and high-dose ZA versus placebo (P = 0.004). Atrial APD30 was lower with high-dose ZA versus placebo, low and medium doses (P < 0.001). Canine ECG study: Mature female beagles received intravenous ZA 0.067 mg/kg or saline (placebo; each n = 6) every 2 weeks for 12 weeks. P wave dispersion was greater in the ZA group (7.7 ± 3.7 vs. 3.4 ± 2.6 ms, P = 0.04). There were no significant differences in P wave index, maximum or minimum P wave duration, or PR interval. CONCLUSION: ZA shortens left atrial APD and ERP and increases P wave dispersion.

"Quick flutter skip": midlife women's descriptions of palpitations.

OBJECTIVE: The objective of this study is to describe peri- and postmenopausal women's experiences of palpitations (quality, frequency, severity, distress, duration and temporal pattern, aura, associated symptoms, and aggravating/alleviating factors) and related healthcare experiences. METHODS: Qualitative descriptive methods were used. Semistructured interviews were conducted with women who reported palpitations and were enrolled in a larger case-control pilot study comparing electrocardiographic results between women with and without palpitations. Authors analyzed women's narratives using standard content analytic procedures. RESULTS: Fourteen participants (mean age, 54.5 y [SD = 4.8 y]; range, 46-62 y; 79% postmenopausal) completed interviews. The interviews revealed that women (a) often had difficulty describing their palpitations until prompted by the interviewer; (b) experienced noteworthy variations in the quality and other dimensions of their palpitations; (c) had a wide variety of healthcare experiences related to their palpitations, including not reporting their symptoms to providers, having providers dismiss their symptoms, and having providers be aware of their symptoms and provide diagnostic tests; and (d) at times, created worst case scenarios (downward shifts) under which they would seek treatment for their palpitations, thus enabling them to minimize their symptoms and avoid healthcare. CONCLUSION: This study advances understanding of how women describe their palpitations and related healthcare experiences. Findings could have implications for building research and clinical tools to guide assessment, communication, and/or education for patients and/or providers about palpitations and for developing and testing behavioral interventions to address this poorly understood symptom in peri- and postmenopausal women.

Cardiac healthcare disparities and electrocardiography (ECG) differences in schizophrenia at end of life.

Schizophrenia is associated with early mortality of 15 to 20 years, and 80 % of deaths are due to cardiovascular disease with a three-times greater risk of sudden-cardiac-death. While lifestyle, medications, genetics, and healthcare disparities are contributing factors, the etiology of this complex process is not fully understood. The aim of this study is to examine cardiac-related healthcare utilization and electrocardiogram (ECG) outcomes in schizophrenia at the end of life (EOL). A cohort of individuals with schizophrenia (SG) (n = 610, ≥50 years) were identified retrospectively from a unified clinical data platform and measures of cardiovascular healthcare utilization were evaluated within a 12-month period prior to death. Similarly, a control group (n = 610) was randomly identified and matched by gender (53 % females) and age of death (72.8 ± 12.4 years). Statistical methods included Cochran-Mantel-Haenszel and mixed-effects logistic & linear regression tests with adjustments for match strata and marital status, race, age, and gender as covariates. Results indicate that SG was more likely to be unmarried, unemployed, or from minority groups (all p < 0.001), and more likely to have diabetes and/or cardiovascular disease (p < 0.001). SG was less likely to receive an ECG (p = 0.001) or cardiac catheterization procedure (p < 0.001). SG had a greater mean QTc (447.2 ms vs. 434.6 ms; p = 0.001) and were twice as likely to have "prolonged QT" on ECG report (p = 0.006). In conclusion, SG had reduced likelihood of cardiac-related healthcare interventions, and despite greater likelihood of prolonged QTc, a recognized biomarker of cardiac risk, ECG was less likely at EOL. Given greater cardiac comorbidity and risk of sudden cardiac death in schizophrenia, improved practice guidelines are needed.

High risk of QT interval prolongation and torsades de pointes associated with intravenous quinidine used for treatment of resistant malaria or babesiosis.

Cardiac toxicity may be associated with drugs used for malaria. Torsades de pointes (TdP) is a well-known adverse effect of quinidine when used for atrial fibrillation. Intravenous quinidine doses for resistant malaria are 2 to 3 times higher than those used for arrhythmias. Among 6 patients receiving quinidine for malaria or babesiosis, 4 developed QT interval prolongation and 2 experienced TdP. Clinicians should be aware that recommended doses of quinidine for malaria carry a high TdP risk.

Athlete ECG T-wave abnormality interpretation patterns by non-experts.

Background: The presence of T-wave abnormalities (TWA) on an athlete's electrocardiogram (ECG) presents as a diagnostic challenge for physicians. Types of TWA patterns classified as abnormal by inexperienced readers have not been systematically analyzed. Methods: ECGs from the 2011-2015 National Football League Scouting Combine (initially interpreted by general cardiologists) were retrospectively reviewed by expert sports cardiologists with strict application of the 2017 International Criteria. Patterns of TWA that were altered from the original interpretation were analyzed. Results: The study included 1643 athletes (mean age 22 years). There was a 67 % reduction in the number of athletes with any TWA (p < 0.001) with 111 ECGs changed to normal. Inferior TWA was the most common interpreted initial ECG abnormality altered followed by anterior and lateral. Discussion: This analysis revealed an initial high rate of TWA by non-expert readers. Tailored education programs to physicians who interpret athlete ECGs should highlight these specific T-wave patterns. We see this as an opportunity to make more clinicians aware of ECG interpretation guidelines as sports trained cardiologists are mostly self-taught.