bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of Increased LDL (Low-Density Lipoprotein) and Decreased Triglycerides With SGLT2 (Sodium-Glucose Cotransporter 2) Inhibition
Authors: Basu Debapriya , Huggins Lesley-Ann , Scerbo Diego , Obunike Joseph , Mullick Adam E. , Rothenberg Paul L. , Di Prospero Nicholas A. , Eckel Robert H. , Goldberg Ira J.
Published: September 2018

Objective—

SGLT2 (sodium-glucose cotransporter 2) inhibition in humans leads to increased levels of LDL (low-density lipoprotein) cholesterol and decreased levels of plasma triglyceride. Recent studies, however, have shown this therapy to lower cardiovascular mortality. In this study, we aimed to determine how SGLT2 inhibition alters circulating lipoproteins.

Approach and Results—

We used a mouse model expressing human CETP (cholesteryl ester transfer protein) and human ApoB100 (apolipoprotein B100) to determine how SGLT2 inhibition alters plasma lipoprotein metabolism. The mice were fed a high-fat diet and then were made partially insulin deficient using streptozotocin. SGLT2 was inhibited using a specific antisense oligonucleotide or canagliflozin, a clinically available oral SGLT2 inhibitor. Inhibition of SGLT2 increased circulating levels of LDL cholesterol and reduced plasma triglyceride levels. SGLT2 inhibition was associated with increased LpL (lipoprotein lipase) activity in the postheparin plasma, decreased postprandial lipemia, and faster clearance of radiolabeled VLDL (very-LDL) from circulation. Additionally, SGLT2 inhibition delayed turnover of labeled LDL from circulation.

Conclusions—

Our studies in diabetic CETP-ApoB100 transgenic mice recapitulate many of the changes in circulating lipids found with SGLT2 inhibition therapy in humans and suggest that the increased LDL cholesterol found with this therapy is because of reduced clearance of LDL from the circulation and greater lipolysis of triglyceride-rich lipoproteins. Most prominent effects of SGLT2 inhibition in the current mouse model were seen with antisense oligonucleotides-mediated knockdown of SGLT2.
Progress toward prevention of cardiovascular disease. A 30-year retrospective.
Authors: Levy R I
Published: September 2018

Since its creation as the National Heart Institute in 1948, the National Heart, Lung, and Blood Institute (NHLBI) has led a national biomedical research program in heart, lung, blood, and blood vessel diseases, and has become increasingly involved in complex clinical trials to validate its research findings. In addition, NHLBI sponsors demonstrations and educational activities to apply proved research findings in the health care community. NHLBI's approach to these responsibilities involves acquiring new and basic information, testing and evaluating the information, and applying it to improve prevention, detection, and treatment of disease. New equipment such as the heart-lung machine and the pacemaker, better diagnostic procedures, new operative and treatment devices, new drugs, and increased use of preventive medicine have dramatically reduced mortality from heart attack, hypertension and stroke.
Characteristics and Outcomes of Pediatric Patients Who Undergo Placement of Implantable Cardioverter Defibrillators
Authors: Baskar Shankar , Bao Haikun , Minges Karl E. , Spar David S. , Czosek Richard J.
Published: September 2018

Background

Implantable cardioverter defibrillators (ICDs) are an important part of therapy for many patients, yet there is little data on population characteristics, complications, or system survival in pediatric patients.

Methods

A retrospective review of ICD recipients in the National Cardiovascular Data Registry ICD Registry was performed from 2010 to 2016. Patient characteristics and complications between pediatric (≤21 years) and adult populations (>21 years) were compared. Variables associated with complications and early device interventions within the pediatric cohort were evaluated using multivariate modeling.

Results

There were 562 209 total ICD implants, of which 3461 occurred in the pediatric cohort. Among the pediatric patients, 60% of implants were for primary prevention, and nonischemic cardiomyopathy was the most common underlying disease (60%). Over time, there was an increasing trend of both primary and secondary prevention ICD implantations (
P
<0.05). Compared with adults, pediatric patients were more likely to have structural heart disease, hypertrophic cardiomyopathy, and channelopathy, and to receive a single-chamber device (all
P
<0.001). There was no difference in inhospital complications between the adult and pediatric cohorts (2.4% versus 2.6%,
P
=0.3). However, among the pediatric patients, lower weight, Ebstein anomaly, worse New York Heart Association class, dual chamber, and cardiac resynchronization therapy-defibrillator were associated with greater risk of complications. Although reintervention for generator replacement or upgrade was more common in adults, the time to reintervention was shorter in the pediatric cohort.

Conclusions

We observed an increasing trend in ICD device implantation among pediatric patients. The pediatric cohort had similar inhospital complication rates compared with adults but had a shorter time to reintervention.
Use of Ablation Index-Guided Ablation Results in High Rates of Durable Pulmonary Vein Isolation and Freedom From Arrhythmia in Persistent Atrial Fibrillation Patients
Authors: Hussein Ahmed , Das Moloy , Riva Stefania , Morgan Maureen , Ronayne Christina , Sahni Ankita , Shaw Matthew , Todd Derick , Hall Mark , Modi Simon , Natale Andrea , Dello Russo Antonio , Snowdon Richard , Gupta Dhiraj
Published: September 2018

Background

Catheter ablation for persistent atrial fibrillation (AF) is associated with less favorable outcomes than for paroxysmal AF. Substrate modification is often added to pulmonary vein isolation (PVI) to try to improve success rates. Recent studies have shown improved clinical outcomes with use of regional ablation index (AI) targets for PVI. We hypothesized that prospective use of AI-guided PVI in persistent AF patients would result in a low rate of PV reconnection at repeat electrophysiology study and that a high success rate can be achieved with durable PVI alone.

Methods

Forty consecutive patients with persistent AF underwent AI-guided PVI with target values of 550 for anterior and 400 for posterior left atrial regions, followed by a protocol-mandated repeat procedure after 2 months. Patients were monitored for atrial tachyarrhythmia recurrence via daily plus symptom-initiated ECG recordings for 12 months. Recurrence was defined as ≥30 seconds of any atrial tachyarrhythmia after a 3-month blanking period.

Results

PV reconnection was seen at repeat electrophysiology study in 22% of patients, affecting 7% of PVs. Ablation on the intervenous carina was required in 44% patients to achieve durable PVI. Atrial tachyarrhythmia recurrence was documented in 8 (20%) patients, only one of whom had PV reconnection at repeat study. At 12 months, 38/40 (95%) patients were in sinus rhythm, with 4 (10%) patients having started antiarrhythmic drugs. Higher body mass index and excess alcohol consumption were the only significant factors associated with atrial tachyarrhythmia recurrence.

Conclusions

Use of AI targets results in a high level of durable PVI. A good clinical outcome can be achieved in the great majority of persistent AF patients with AI-guided PVI alone.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02628730.
Unifocal Right-Sided Ablation Treatment for Neurally Mediated Syncope and Functional Sinus Node Dysfunction Under Computed Tomographic Guidance
Authors: Debruyne Philippe , Rossenbacker Tom , Collienne Christine , Roosen John , Ector Bavo , Janssens Luc , Charlier Filip , Vankelecom Bart , Dewilde Willem , Wijns William
Published: September 2018

Background

Biatrial, extensive, and complex ablation strategies have been published for the treatment of neurally mediated syncope, sinus node dysfunction, and functional atrioventricular block. We have developed a less extensive and more specific approach compared with previously published cardioneuroablation strategies, called cardio-neuromodulation. It is based on tailored vagolysis of the sinoatrial node through partial ablation of the anterior right-ganglionated plexus, preferentially through a right-sided approach.

Methods

Patients with syncope were enrolled between December 2016 and December 2017. They were assigned to group A if they had a positive head-up tilt test and to group B if they presented with a pause ≥3 seconds. The area to target during cardio-neuromodulation was designed offline on a computed tomographic scan. Slow heart rates and pauses were compared during 24-hour rhythm registration at baseline, at 1-month follow-up, and 6-month follow-up. Syncope burden was assessed before the procedure and at 3- and 6-month follow-up.

Results

Twenty patients underwent cardio-neuromodulation through a right-sided approach (12 in group A, 8 in group B). The first application of radiofrequency energy led to a P-P interval shortening >120 ms in all 20 patients. After a mean±SD ablation time of 7±4 minutes and mean ablated surface area of 11±6 mm
2
, the P-P interval shortened by 219±160 ms (
P
<0.001). The number of beats <50/min during 24-hour rhythm registration was reduced by a median of 100% at 6-month follow-up (
P
<0.001). Syncope burden was reduced by 95% at 6-month follow-up (
P
<0.001).

Conclusions

These data indicate that cardio-neuromodulation, through a right-sided and computed tomographic–guided procedure, is safe, fast, and highly reproducible in preventing inappropriate functional sinus bradycardia and syncope recurrence.
Slow/Fast Atrioventricular Nodal Reentrant Tachycardia Using the Inferolateral Left Atrial Slow Pathway
Authors: Stavrakis Stavros , Jackman Warren M. , Lockwood Deborah , Nakagawa Hiroshi , Beckman Karen , Elkholey Khaled , Wang Zulu , Po Sunny S.
Published: September 2018

Background

We describe a technique to localize the ablation target in patients with an unusual variant of slow/fast atrioventricular nodal reentrant tachycardia (AVNRT) using a slow pathway connecting to the basal inferolateral left atrium.

Methods

Consecutive patients with slow/fast AVNRT were included. During stable slow/fast AVNRT, a single late atrial extrastimulus (AES) was delivered at the inferolateral left atrium near the mitral annulus. Advancing the next His bundle potential by ≥5 ms, followed by resetting of the tachycardia cycle length, indicated that the AES engaged the anterograde slow pathway. The latest AES resetting AVNRT was considered to be in close proximity to the atrial end of the anterograde slow pathway and was selected as the ablation target.

Results

In 10 of 843 (1.2%) patients, ablation at the inferolateral left atrium was required. All patients had had failed ablation at the inferior triangle of Koch and roof of the coronary sinus. In all 10 patients, a late AES advanced the His bundle potential by ≥10 ms and reset the tachycardia. Ablation at that site eliminated slow pathway conduction and terminated the tachycardia. Ablation was successful at the site of the latest AES, delivered 49±12 ms after the onset of the His bundle potential. No recurrent tachycardia was noted at 1 year of follow-up.

Conclusions

The inferolateral left atrium slow pathway is used in a small subset of patients with slow/fast AVNRT. Accurate localization of the ablation target can be achieved by delivering late AES during AVNRT (resetting response).
Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Heart Transplant Recipients
Authors: Arora Satish , Andreassen Arne K. , Karason Kristjan , Gustafsson Finn , Eiskjær Hans , Bøtker Hans Erik , Rådegran Göran , Gude Einar , Ioanes Dan , Solbu Dag , Dellgren Göran , Ueland Thor , Aukrust Pål , Gullestad Lars ,   on behalf of the SCHEDULE (Scandinavian Heart Transplant Everolimus De Novo Study With Early Calcineurin Inhibitors Avoidance) Investigators
Published: September 2018

Background

Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation, and the effect of different immunosuppressive regimens on CAV is not fully understood. The randomized SCHEDULE trial (Scandinavian Heart Transplant Everolimus De Novo Study With Early Calcineurin Inhibitors Avoidance) evaluated whether initiation of the proliferation signal inhibitor everolimus and early cyclosporine elimination can reduce CAV development.

Methods and Results

The SCHEDULE trial was a multicenter Scandinavian trial, where 115 de novo heart transplantation recipients were randomized to everolimus with complete cyclosporine withdrawal 7 to 11 weeks after heart transplantation or standard cyclosporine-based immunosuppression. Seventy-six (66%) patients had matched intravascular ultrasound examinations at baseline and 12 and 36 months. Intravascular ultrasound analysis evaluated maximal intimal thickness, percent atheroma volume, and total atheroma volume. Qualitative plaque analysis using virtual histology assessed fibrous, fibrofatty, and calcified tissue as well as necrotic core. Serum inflammatory markers were measured in parallel. The everolimus group (n=37) demonstrated significantly reduced CAV progression as compared with the cyclosporine group (n=39) at 36 months (Δ maximal intimal thickness, 0.09±0.05 versus 0.15±0.16 mm [
P
=0.03]; Δ percent atheroma volume, 5.3±2.8% versus 7.6±5.9% [
P
=0.03]; and Δ total atheroma volume, 33.9±71.2 versus 54.2±96.0 mm
3
[
P
=0.34], respectively]. At 36 months the number of everolimus patients with rejection graded ≥2R was 15 (41%) as compared with 5 (13%) in the cyclosporine group (
P
=0.01). Everolimus did not affect CAV morphology or immune marker activity during the follow-up period.

Conclusions

The SCHEDULE trial demonstrates that everolimus initiation and early cyclosporine elimination significantly reduces CAV progression at 12 months, and this beneficial effect is clearly sustained at 36 months.

Clinical trial registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01266148.
Phosphodiesterase-5 Is Elevated in Failing Single Ventricle Myocardium and Affects Cardiomyocyte Remodeling In Vitro
Authors: Garcia Anastacia M. , Nakano Stephanie J. , Karimpour-Fard Anis , Nunley Karin , Blain-Nelson Penny , Stafford Natalie M. , Stauffer Brian L. , Sucharov Carmen C. , Miyamoto Shelley D.
Published: September 2018

Background

Single ventricle (SV) congenital heart disease is fatal without intervention, and eventual heart failure is a major cause of morbidity and mortality. Although there are no proven medical therapies for the treatment or prevention of heart failure in the SV heart disease population, phosphodiesterase-5 inhibitors (PDE5i), such as sildenafil, are increasingly used. Although the pulmonary vasculature is the primary target of PDE5i therapy in patients with SV heart disease, the effects of PDE5i on the SV heart disease myocardium remain largely unknown. We sought to determine PDE5 expression and activity in the single right ventricle of SV heart disease patients relative to nonfailing controls and to determine whether PDE5 impacts cardiomyocyte remodeling using a novel serum-based in vitro model.

Methods and Results

PDE5 expression (n=9 nonfailing; n=7 SV heart disease), activity (n=8 nonfailing; n=9 SV heart disease), and localization (n=3 SV heart disease) were determined in explanted human right ventricle myocardium. PDE5 is expressed in SV heart disease cardiomyocytes, and PDE5 protein expression and activity are increased in SV heart disease right ventricle compared with nonfailing right ventricle. Isolated neonatal rat ventricular myocytes were treated for 72 hours with nonfailing or SV heart disease patient serum±sildenafil. Reverse transcription quantitative polymerase chain reaction (n=5 nonfailing; n=12 SV heart disease) and RNA sequencing (n=3 nonfailing; n=3 SV heart disease) were performed on serum-treated neonatal rat ventricular myocytes and demonstrated that treatment with SV heart disease sera results in pathological gene expression changes that are attenuated with PDE5i.

Conclusions

PDE5 is increased in failing SV heart disease myocardium, and pathological gene expression changes in SV heart disease serum-treated neonatal rat ventricular myocytes are abrogated by PDE5i. These results suggest that PDE5 represents an intriguing myocardial therapeutic target in this population.
Validity of Performance and Outcome Measures for Heart Failure
Authors: Patel Jay , Sandhu Alex , Parizo Justin , Moayedi Yasbanoo , Fonarow Gregg C. , Heidenreich Paul A.
Published: September 2018

Background

Numerous quality metrics for heart failure (HF) care now exist based on process and outcome. What remains unclear, however, is if the correct quality metrics are being emphasized. To determine the validity of certain measures, we compared correlations between measures and reliability over time. Measures assessed include guideline-recommended β-blocker (BB), any BB, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker, mineralocorticoid receptor antagonist, and hydralazine/isosorbide dinitrate (in blacks) use among candidates, 30-day mortality, 1-year mortality, and 30-day readmission.

Methods and Results

This was an observational cohort analysis using chart review and electronic resources for 55 735 patients from 102 Veterans Affairs medical centers hospitalized with HF from 2008 to 2013. Assessments of convergent validity and reliability were performed. Significant correlations were found between in-hospital rates of ACE inhibitor use and the following measures: BB use, 30-day mortality, and 1-year mortality. Guideline-recommended BB use was also significantly correlated with mineralocorticoid receptor antagonists, 30-day mortality, and 1-year mortality. There was no correlation between 30-day readmission rates and any therapy or mortality. Measure reliability over time was seen for guideline-recommended BBs (
r
=0.57), mineralocorticoid receptor antagonists (
r
=0.50), 30-day mortality (
r
=0.29), and 1-year mortality (
r
=0.31). ACE inhibitor and readmission rates were not reliable measures over time.

Conclusions

BB use, ACE inhibitor use, mortality, and mineralocorticoid receptor antagonist use are valid measures of HF quality. Thirty-day readmission rate did not seem to be a valid measure of HF quality of care. If the goal is to identify high-quality HF care, the emphasis on decreasing readmission rates might be better directed towards improving usage of the recommended therapies.
Incident Atrial Fibrillation Is Associated With
MYH7
Sarcomeric Gene Variation in Hypertrophic Cardiomyopathy
Authors: Lee Seung-Pyo , Ashley Euan A. , Homburger Julian , Caleshu Colleen , Green Eric M. , Jacoby Daniel , Colan Steven D. , Arteaga-Fernández Edmundo , Day Sharlene M. , Girolami Francesca , Olivotto Iacopo , Michels Michelle , Ho Carolyn Y. , Perez Marco V. ,   on behalf of the SHaRe Investigators
Published: September 2018

Background

Although atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM) patients, the relationship between genetic variation and AF has been poorly defined. Characterizing genetic subtypes of HCM and their associations with AF may help to improve personalized medical care. We aimed to investigate the link between sarcomeric gene variation and incident AF in HCM patients.

Methods and Results

Patients from the multinational Sarcomeric Human Cardiomyopathy Registry were followed for incident AF. Those with likely pathogenic or pathogenic variants in sarcomeric genes were included. The AF incidence was ascertained by review of medical records and electrocardiograms at each investigative site. One thousand forty adult HCM patients, without baseline AF and with likely pathogenic or pathogenic variation in either
MYH7
(n=296),
MYBPC3
(n=659), or thin filament genes (n=85), were included. Compared with patients with variation in other sarcomeric genes, those with
MYH7
variants were younger on first clinical encounter at the Sarcomeric Human Cardiomyopathy Registry site and more likely to be probands than the
MYBPC3
variants. During an average follow-up of 7.2 years, 198 incident AF events occurred. Patients with likely pathogenic or pathogenic mutations in
MYH7
had the highest incidence of AF after adjusting for age, sex, proband status, left atrial size, maximal wall thickness, and peak pressure gradient (hazard ratio, 1.7; 95% CI, 1.1–2.6;
P
=0.009).

Conclusions

During a mean follow-up of 7.2 years, new-onset AF developed in 19% of HCM patients with sarcomeric mutations. Compared with other sarcomeric genes, patients with likely pathogenic or pathogenic variation in
MYH7
had a higher rate of incident AF independent of clinical and echocardiographic factors.
Association Between 30-Day Mortality After Percutaneous Coronary Intervention and Education and Certification Variables for New York State Interventional Cardiologists
Authors: Khatana Sameed Ahmed M. , Fiorilli Paul N. , Nathan Ashwin S. , Kolansky Daniel M. , Mitra Nandita , Groeneveld Peter W. , Giri Jay
Published: September 2018

Background:

Patients and other providers have access to few publicly available physician attributes that identify interventional cardiologists with better postprocedural outcomes, particularly in states without public reporting of outcomes. Interventional cardiology board certification, maintenance of certification, graduation from a US medical school, medical school ranking, and length of practice represent such publicly available attributes. Previous studies on these measures have shown mixed results.

Methods and Results:

We included interventional cardiologists practicing in New York State in the years 2011 to 2013. The primary outcome was 30-day risk-standardized mortality rate (RSMR) after percutaneous coronary intervention. Hierarchical regression modeling was used to analyze the physician attributes and was adjusted for provider caseload. A total of 356 providers were studied. The average 30-day RSMR was 1.1 (SD=0.1) deaths per 100 cases for all percutaneous coronary interventions and 0.7 (SD=0.1) deaths per 100 cases for nonemergent procedures. The primary outcome was slightly lower among providers with interventional cardiology board certification compared with noncertified providers (1.06 [SD=0.14] versus 1.14 [SD=0.14] deaths per 100 cases;
P
<0.001). In multivariable hierarchical regression modeling, after adjusting for provider caseload, none of the physician attributes were associated with the primary outcome. Provider caseload was significantly associated with 30-day RSMR independent of the other attributes.

Conclusions:

Interventional cardiology board-certified providers had a modestly lower 30-day RSMR before accounting for caseload. However, after adjusting for provider caseload, none of the examined publicly available physician attributes, including interventional cardiology board certification, were independently associated with 30-day RSMR.
One-Year Survival After ST-Segment–Elevation Myocardial Infarction in Relation With Prehospital Administration of Dual Antiplatelet Therapy
Authors: Danchin Nicolas , Puymirat Etienne , Cayla Guillaume , Cottin Yves , Coste Pierre , Gilard Martine , Goldstein Patrick , Braun François , Belle Loic , Montalescot Gilles , Ferrières Jean , Schiele François , Simon Tabassome ,   for the FAST-MI Investigators
Published: September 2018

Background

The optimal timing of administration of dual antiplatelet therapy (DAPT) in acute ST-segment–elevation myocardial infarction patients is debated. Clinical trials have failed to demonstrate the superiority of pretreatment with P2Y12 inhibitors in ST-segment–elevation myocardial infarction, but they were not designed to assess hard clinical end points. We used data from the FAST-MI (French Registry on Acute ST-Segment–Elevation or Non-ST-Segment–Elevation Myocardial Infarction) cohorts to determine 1-year survival and in-hospital outcomes in patients receiving DAPT, comparing prehospital versus in-hospital administration.

Methods and Results

The FAST-MI program collects extensive data on patients admitted in France for acute myocardial infarction over a 1-month period every 5 years since 2005. For the present analysis, 3548 patients with ST-segment–elevation myocardial infarction ≤12 hours from symptom onset, transported by physician-staffed emergency medical system ambulances, not treated with intravenous fibrinolysis, and receiving DAPT were included, of whom 44% received DAPT in the ambulance. The primary end point was 1-year survival as assessed by multivariate Cox analysis and propensity score analysis. In-hospital bleeding and ischemic complications were also analyzed. Adjusted in-hospital mortality was numerically but not significantly lower in patients with prehospital DAPT. There were no differences in in-hospital bleeding complications. Fully-adjusted hazard ratio for 1-year death in patients with prehospital versus in-hospital DAPT was 0.69 (95% CI, 0.51–0.92;
P
=0.011), and propensity score–adjusted hazard ratio was 0.55 (95% CI, 0.41–0.73;
P
=0.001) in the whole population. In the propensity score–matched cohorts (360 patients each), 1-year survival was 93.9% in patients with prehospital versus 90.3% in those with in-hospital DAPT (hazard ratio, 0.62; 95% CI, 0.36–1.05;
P
=0.077). Results were consistent in subgroups, including by year of survey, age, presence of out-of-hospital cardiac arrest, morphine use, and type of P2Y12 inhibitor used.

Conclusions

In these cohorts of ST-segment–elevation myocardial infarction patients considered for primary percutaneous coronary intervention, prehospital administration of DAPT was associated with higher 1-year survival and no increase in in-hospital bleeding complications. The magnitude of the decrease in 1-year mortality, however, may suggest the persistence of some degree of residual confounding.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifiers: NCT00673036, NCT01237418, and NCT02566200.
COMPASS-CP: An Electronic Application to Capture Patient-Reported Outcomes to Develop Actionable Stroke and Transient Ischemic Attack Care Plans
Authors: Duncan Pamela W. , Abbott Rica M. , Rushing Scott , Johnson Anna M. , Condon Christina N. , Lycan Sarah L. , Lutz Barbara J. , Cummings Doyle M. , Pastva Amy M. , D’Agostino Ralph B. , Stafford Jeanette M. , Amoroso Robert M. , Jones Sara B. , Psioda Matthew A. , Gesell Sabina B. , Rosamond Wayne D. , Prvu-Bettger Janet , Sissine Mysha E. , Boynton Mark D. , Bushnell Cheryl D. ,   for the COMPASS Investigative Team
Published: September 2018

Background

Patient-reported outcomes (PROs) are clinical tools that measure patients’ goals of care and assess patient-reported physical, mental, and social well-being. Despite their value in advancing patient-centered care, routine use of PROs in stroke management has lagged. As part of the pragmatic COMPASS (Comprehensive Post-Acute Stroke Services) trial, we developed COMPASS-Care Plan (CP), a clinician-facing application that captures and analyzes PROs for stroke and transient ischemic attack patients discharged home and immediately generates individualized electronic CP. In this report, we (1) present our methods for developing and implementing COMPASS-CP PROs, (2) provide examples of CP generated from COMPASS-CP, (3) describe key functional, social, and behavioral determinants of health captured by COMPASS-CP, and (4) report on clinician experience with using COMPASS-CP in routine clinical practice for care planning and engagement of stroke and transient ischemic attack patients discharged home.

Methods and Results

We report on the first 871 patients enrolled in 20 North Carolina hospitals randomized to the intervention arm of COMPASS between July 2016 and February 2018; these patients completed a COMPASS follow-up visit within 14 days of hospital discharge. We also report user satisfaction results from 56 clinicians who used COMPASS-CP during these visits. COMPASS-CP identified more cognitive and depression deficits than physical deficits. Within 14-day posthospitalization, less than half of patients could list the major risk factors for stroke, 36% did not recognize blood pressure as a stroke risk factor, and 19% of patients were nonadherent with prescribed medications. Three-fourths of clinicians reported that COMPASS-CP identifies important factors impacting patients’ recovery that they otherwise may have missed, and two-thirds were highly satisfied with COMPASS-CP.

Conclusions

The COMPASS-CP application meets an immediate need to incorporate PROs into the clinical workflow to develop patient-centered CP for stroke patients and has high user satisfaction.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02588664.
Psychological Distress and Risk of Myocardial Infarction and Stroke in the 45 and Up Study
Authors: Jackson Caroline A. , Sudlow Cathie L.M. , Mishra Gita D.
Published: September 2018

Background

The interplay between mental and physical health remains poorly understood. We investigated whether psychological distress is associated with risk of myocardial infarction (MI) and stroke in a population-based prospective study.

Methods and Results

We included participants without prior stroke/MI from the New South Wales 45 and Up Study. We categorized baseline psychological distress as low, medium, and high/very high on the 10-item Kessler Psychological Distress scale and identified stroke and MI through linkage to hospital admission and mortality records. We obtained sex and age-stratified adjusted and unadjusted hazard ratios for the association between psychological distress and MI and stroke. We investigated for interaction between psychological distress and each of age and sex. Among 221 677 participants, 16.2% and 7.3% had moderate and high/very high psychological distress at recruitment, respectively. During 4.7 (±0.98 SD) years of follow-up, 4573 MIs and 2421 strokes occurred. Absolute risk of MI and stroke increased with increasing psychological distress level. In men aged 45 to 79 years, high/very high versus low psychological distress was associated with a 30% increased risk of MI (fully adjusted hazard ratios, 1.30; 95% CI, 1.12–1.51), with weaker estimates in those aged ≥80 years. Among women, high/very high psychological distress was associated with an 18% increased risk of MI (adjusted hazard ratio, 1.18; 95% CI, 0.99–1.42) with similar findings across age groups. In the age group of participants aged 45 to 79 years, high/very high psychological distress and male sex had a supra-additive effect on MI risk. Similar estimates were observed for stroke, with high/very high psychological distress associated with a 24% and 44% increased stroke risk in men and women, respectively, with no evidence of interaction with age or sex.

Conclusions

Psychological distress has a strong, dose-dependent, positive association with MI and stroke in men and women, despite adjustment for a wide range of confounders.
Predicting Length of Stay and the Need for Postacute Care After Acute Myocardial Infarction to Improve Healthcare Efficiency
Authors: Wasfy Jason H. , Kennedy Kevin F. , Masoudi Frederick A. , Ferris Timothy G. , Arnold Suzanne V. , Kini Vinay , Peterson Pamela , Curtis Jeptha P. , Amin Amit P. , Bradley Steven M. , French William J. , Messenger John , Ho P. Michael , Spertus John A.
Published: September 2018

Background

To improve value in the care of patients with acute myocardial infarction (MI), payment models increasingly hold providers accountable for costs. As such, providers need tools to predict length of stay (LOS) during hospitalization and the likelihood of needing postacute care facilities after discharge for acute MI patients. We developed models to estimate risk for prolonged LOS and postacute care for acute MI patients at time of hospital admission to facilitate coordinated care planning.

Methods and Results

We identified patients in the National Cardiovascular Data Registry ACTION registry (Acute Coronary Treatment and Intervention Outcomes Network) who were discharged alive after hospitalization for acute MI between July 1, 2008 and March 31, 2017. Within a 70% random sample (Training cohort) we developed hierarchical, proportional odds models to predict LOS and hierarchical logistic regression models to predict discharge to postacute care. Models were validated in the remaining 30%. Of 633 737 patients in the Training cohort, 16.8% had a prolonged LOS (≥7 days) and 7.8% were discharged to a postacute facility (extended care, a transitional care unit, or rehabilitation). Model discrimination was moderate in the validation dataset for predicting LOS (C statistic=0.640) and strong for predicting discharge to postacute care (C statistic=0.827). For both models, discrimination was similar in ST-segment–elevation MI and non–ST-segment–elevation MI subgroups and calibration was excellent.

Conclusions

These models developed in a national registry can be used at the time of initial hospitalization to predict LOS and discharge to postacute facilities. Prospective testing of these models is needed to establish how they can improve care coordination and lower costs.
First Medical Contact-to-Device Time and Heart Failure Outcomes Among Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Loh Joshua P. , Tan Li-Ling , Zheng Huili , Lau Yee-How , Chan Siew-Pang , Tan Kelvin-Bryan , Chua Terrance , Tan Huay-Cheem , Foo David , Lee Chee-Wan , Tong Khim-Leng , Foo Ling-Li , Hausenloy Derek , Sahlen Anders , Yeo Khung-Keong , Fox Keith A.A. , Wang Tracy Y. , Richards A. Mark , Chan Mark Y.
Published: September 2018

Background

Expediting reperfusion during primary percutaneous coronary intervention is aimed at salvaging myocardium in ST-segment–elevation myocardial infarction. Few studies have examined the relation between reperfusion time and heart failure (HF) events.

Methods and Results:

We studied 7597 patients undergoing primary percutaneous coronary intervention from 2007 to 2013 in the Singapore Myocardial Infarct Registry, which captures HF at admission, postadmission in-hospital HF, and HF rehospitalization. We studied the relation of first medical contact to deployment of first device to achieve reperfusion (FTD) time with in-hospital HF events and HF rehospitalization, with mortality modeled as a competing risk. At the population level, median FTD time decreased from 91 minutes (interquartile range, 69–114) in 2007 to 58 minutes (45–75) in 2013 (
P
=0.001), whereas mortality remained unchanged (in-hospital: range 5.3%–7.3%;
P
=0.190 and 1-year: range 7.8%–10.9%;
P
=0.505). HF at admission increased from 12.2% in 2007 to 18.4% in 2013,
P
=0.020, whereas postadmission in-hospital HF decreased from 12.8% in 2007 to 7.1% in 2013,
P
=0.030. HF rehospitalization increased from 1.2% in 2007 to 2.6% in 2013 (
P
=0.003), for 30-day HF rehospitalization, and 3.8% in 2007 to 5.6% in 2013 (
P
=0.037), for 1-year HF rehospitalization. At the individual level, among patients with HF at admission (N=1191), longer FTD time was associated with more 30-day HF rehospitalization (compared with ≤60 minutes, adjusted hazard ratio, 1.68 [0.73–3.86] for 60–90 minutes, 2.88 [1.19–6.92], for 90–120 minutes, and 2.84 [1.08–7.44] for >120 minutes). Longer FTD time was associated with a greater risk of postadmission in-hospital HF (compared with ≤60 minutes, adjusted hazard ratio, 1.18 [0.96–1.44] for 60–90 minutes, 1.59 [1.25–2.03] for 90–120 minutes, and 1.67 [1.26–2.21] for >120 minutes).

Conclusions:

Temporal reductions in FTD time were associated with decrease in postadmission in-hospital HF. Among patients presenting with HF at admission, delays in FTD beyond 90 minutes were associated with more 30-day HF rehospitalization.
Gender Disparities Among Adult Recipients of Bystander Cardiopulmonary Resuscitation in the Public
Authors: Blewer Audrey L. , McGovern Shaun K. , Schmicker Robert H. , May Susanne , Morrison Laurie J. , Aufderheide Tom P. , Daya Mohamud , Idris Ahamed H. , Callaway Clifton W. , Kudenchuk Peter J. , Vilke Gary M. , Abella Benjamin S. ,   Resuscitation Outcomes Consortium (ROC) Investigators
Published: September 2018

Background:

Bystander cardiopulmonary resuscitation (BCPR) improves survival from out-of-hospital cardiac arrest (OHCA), yet BCPR rates remain low. It is unknown whether BCPR delivery disparities exist based on victim gender. We measured BCPR rates by gender in private and public environments, hypothesizing that females would be less likely than males to receive BCPR in public settings, with an associated difference in survival to hospital discharge.

Methods and Results:

We analyzed data from adult, nontraumatic OHCA events within the Resuscitation Outcomes Consortium registry (2011–2015). Using logistic regression, we modeled the likelihood of receiving BCPR by gender, including patient-level variables, stratified by location. A cohort of 19 331 OHCAs was assessed. Mean age was 64±17 years, and 63% (12 225/19 331) were male. Overall, 37% of OHCA victims received bystander CPR. In public locations, 39% (272/694) of females and 45% (1170/2600) of males received BCPR (
P
<0.01), whereas in private settings, 35% (2198/6328) of females and 36% (3364/9449) of males received BCPR (
P
=NS). Among public OHCAs, males had significantly increased odds of receiving BCPR compared with females (odds ratio, 1.27; 95% CI, 1.05–1.53;
P
=0.01); this was not the case in the private setting (odds ratio, 0.93; 95% CI, 0.87–1.01;
P
=NS). Controlling for site, age, and race, BCPR was significantly associated with survival to hospital discharge (odds ratio, 1.69; 95% CI, 1.54–1.85;
P
<0.01); in this model, males had 29% increased odds of survival compared with females (odds ratio, 1.29; 95% CI, 1.17–1.42;
P
<0.01).

Conclusions:

Males had an increased likelihood of receiving BCPR compared with females in public. BCPR improved survival to discharge, with greater survival among males compared with females.
Cardiac Imaging in Patients With Ventricular Tachycardia
Authors: Mahida Saagar , Sacher Frédéric , Dubois Rémi , Sermesant Maxime , Bogun Frank , Haïssaguerre Michel , Jaïs Pierre , Cochet Hubert
Published: September 2018

Ventricular tachycardia (VT) is a major cause of sudden cardiac death. The majority of malignant VTs occur in patients with structural heart disease. Multimodality imaging techniques play an integral role in determining the underlying etiology and prognostic significance of VT. In recent years, advances in imaging technology have enabled characterization of the structural arrhythmogenic substrate in patients with VT with increasing precision. In parallel with these advances, the role of cardiac imaging has expanded from a largely diagnostic tool to an adjunctive tool to guide interventional approaches for treatment of VT. Invasive and noninvasive imaging techniques, often used in combination, have made it possible to integrate structural and electrophysiological information during VT ablation procedures. An important area of current development is the use of noninvasive imaging techniques based on body surface electrocardiographic mapping to elucidate the mechanisms of VT. In the future, these techniques may provide a priori information on mechanisms of VT in patients undergoing interventional procedures. This review provides an overview of the role of cardiac imaging in patients with VT.
Linking Heart Failure to Cancer
Authors: Bertero Edoardo , Canepa Marco , Maack Christoph , Ameri Pietro
Published: September 2018

Recent epidemiological analyses suggest that incident cancer may be more common among patients with preexisting heart failure (HF) than in patients without HF. Arguments against this notion have been the increased chance of co-occurrence of 2 high-prevalence conditions and increased tumor detection in patients with HF because of intensified medical observation. However, biological data lend support to the hypothesis that HF is an oncogenic condition. Neurohormonal activation has been related to cancer initiation, progression, and dissemination by studies not specifically focusing on HF, which are now reappraised in the light of the emerging evidence that tumors are diagnosed more often in HF than control cohorts. Furthermore, a thought-provoking scenario to be considered is that a systemically perturbed milieu, where low-grade inflammation plays a primary role, leads to both HF and malignancy, thus connecting 1 disease to another. Postischemic HF has been shown to promote tumor growth in an animal model. Exploring these and other pathways potentially linking HF to malignancy is a new and exciting field of research, with the ultimate goal of answering the question of whether HF does promote cancer.
Neonatal Heart Regeneration
Authors: Lam Nicholas T. , Sadek Hesham A.
Published: September 2018

Background:

The adult mammalian heart is incapable of meaningful functional recovery after injury, and thus promoting heart regeneration is 1 of the most important therapeutic targets in cardiovascular medicine. In contrast to the adult mammalian heart, the neonatal mammalian heart is capable of regeneration after various types of injury. Since the first report in 2011, a number of groups have reported their findings on neonatal heart regeneration. The current review provides a comprehensive analysis of heart regeneration studies in neonatal mammals conducted to date, outlines lessons learned, and poses unanswered questions.

Methods:

We performed a PubMed search using the keywords “neonatal” and “heart” and “regeneration.” In addition, we assessed all publications that cited the first neonatal heart regeneration reports: Porrello et al,
Science
, Feb 2011 for apical resection injury; Porrello et al,
PNAS
, Dec 2012 for coronary ligation injury; and Mahmoud et al,
Nature Methods
, Jan 2014 for surgical methodology. Publications were examined for surgical models used, timing of surgery, and postinjury assessment including anatomic, histological, and functional assessment, as well as conclusions drawn.

Results:

We found 30 publications that performed neonatal apical resection, 19 publications that performed neonatal myocardial infarction by coronary artery ligation, and 6 publications that performed cryoinjury using liquid nitrogen–cooled metal probes. Both apical resection and ischemic infarction injury in neonatal mice result in a robust regenerative response, mediated by cardiomyocyte proliferation. On the other hand, several reports have demonstrated that cryoinjury is associated with incomplete heart regeneration in neonatal mice. Not surprisingly, several studies suggest that injury size, as well as surgical and histological techniques, can strongly influence the observed regenerative response and final conclusions. Studies have utilized these neonatal cardiac injury models to identify factors that either inhibit or stimulate heart regeneration.

Conclusions:

Overall, there is consensus that both apical resection and coronary ligation injuries during the first 2 days of life result in heart regeneration in neonatal mammals, whereas cryoinjury was not associated with a similar regenerative response. This regenerative response is mediated by proliferation of preexisting cardiomyocytes, and is modifiable by injury size and surgical technique, as well as metabolic, immunologic, genetic, and environmental factors.
Antithrombotic Therapy in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Undergoing Percutaneous Coronary Intervention
Authors: Angiolillo Dominick J. , Goodman Shaun G. , Bhatt Deepak L. , Eikelboom John W. , Price Matthew J. , Moliterno David J. , Cannon Christopher P. , Tanguay Jean-Francois , Granger Christopher B. , Mauri Laura , Holmes David R. , Gibson C. Michael , Faxon David P.
Published: September 2018

The optimal antithrombotic treatment regimen for patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation represents a challenge in clinical practice. In 2016, an updated opinion of selected experts from the United States and Canada on the treatment of patients with atrial fibrillation undergoing percutaneous coronary intervention was reported. After the 2016 North American consensus statement on the management of antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention, results of pivotal clinical trials assessing the type of oral anticoagulant agent and the duration of antiplatelet treatment have been published. On the basis of these results, this focused update on the antithrombotic management of patients with atrial fibrillation undergoing percutaneous coronary intervention recommends that a non–vitamin K antagonist oral anticoagulant be preferred over a vitamin K antagonist as the oral anticoagulant of choice. Moreover, a double-therapy regimen (oral anticoagulant plus single antiplatelet therapy with a P2Y
12
inhibitor) by the time of hospital discharge should be considered for most patients, whereas extending the use of aspirin beyond hospital discharge (ie, triple therapy) should be considered only for selected patients at high ischemic/thrombotic and low bleeding risks and for a limited period of time. The present document provides a focused updated on the rationale for the new expert consensus–derived recommendations on the antithrombotic management of patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention.
Safety of Nifedipine in Patients With Hypertension
Authors: Stason William B. , Schmid Christopher H. , Niedzwiecki Donna , Whiting Gregory W. , Luo Donghan , Ross Susan D. , Chalmers Thomas C.
Published: September 2018

Abstract
Our objective was to compare cardiovascular event rates in patients with mild or moderate hypertension who received nifedipine with active drug controls. We performed a MEDLARS search using the MeSH heading “hypertension” and the text word “nifedipine” to identify all articles that were published between 1966 and August 1995 in English, French, German, Italian, and Spanish languages and that involved human subjects. The computerized search was supplemented by a manual search of article bibliographies. Review of 1880 citations revealed 98 randomized controlled clinical trials that met protocol criteria. Articles were extracted independently by two doctors who were blinded for author, institution, and treatment regimen, using a structured, pretested extraction form. Differences of opinion were resolved by consensus. Fourteen events occurred in 5198 exposures (0.27%) to nifedipine and 24 events in 5402 exposures (0.44%) to other active drug controls. Unadjusted odds ratios for nifedipine versus controls were 0.49 (95% confidence interval [CI], 0.22-1.09) for definitive events (death, nonfatal myocardial infarction or stroke, revascularization procedure) and 0.61 (95% CI, 0.31-1.17) for all events (definitive plus increased angina). The odds ratio for nifedipine monotherapy (sustained- or extended-release in 91% of exposures) was nonsignificantly higher for definitive and all events (odds ratio, 1.40; 95% CI, 0.49-4.03 and odds ratio, 1.39; 95% CI, 0.59-3.32, respectively). The odds ratio for nifedipine in combination with another drug was significantly lower for definitive and all events (odds ratio, 0.09; 95% CI, 0.01-0.66 and odds ratio, 0.15; 95% CI, 0.03-0.65, respectively). Differences in odds ratio for nifedipine monotherapy and combined therapy were statistically significant (
P
=.02 for definitive events and
P
=.001 for all events). Results support the safety of sustained- and extended-release nifedipine in the treatment of mild or moderate hypertension when it is used in combination with other drugs.