Journal: JAMA Cardiol

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Abstract

Food Insecurity Among Individuals With Cardiovascular Disease and Cardiometabolic Risk Factors Across Race and Ethnicity in 1999-2018.

Brandt EJ, Chang T, Leung C, Ayanian JZ, Nallamothu BK
Importance
Food insecurity is a risk factor for poor cardiovascular outcomes that occur disproportionately among individuals from racial and ethnic minority backgrounds who have cardiovascular disease (CVD) or cardiometabolic risk factors.
Objective
To assess long-term prevalence of food insecurity among those with CVD or cardiometabolic risk factors in the United States.
Design, setting, and participants
This serial cross-sectional study includes data for noninstitutionalized US adults from the National Health and Nutrition Examination Survey (1999-2018).
Main outcomes and measures
Food insecurity was assessed using the US Department of Agriculture Adult Food Security Survey Module. We estimated prevalence of food insecurity among adults with prior CVD (myocardial infarction, stroke, heart failure) and cardiometabolic risk factors (hypertension, diabetes, obesity, hyperlipidemia) across racial and ethnic groups and prevalence of Supplemental Nutrition Assistance Program (SNAP) participation among those reporting food insecurity.
Results
In the analytic sample of 57 517 adults, 6770 individuals (11.8%) reported food insecurity, which was more prevalent among Hispanic (1938 [24.0%]) and non-Hispanic Black (1202 [18.2%]) than non-Hispanic Asian (100 [8.0%]) and non-Hispanic White adults (3221 [8.5%]). Among 57 517 adults, 4527 (7.9%) had any CVD, 2933 (5.1%) coronary artery disease, 1536 (2.7%) stroke, 1363 (2.4%) heart failure, 28 528 (49.6%) hypertension, 17 979 (33.2%) obesity, 6418 (11.2%) diabetes, and 19 178 (30.8%) dyslipidemia. All CVD and cardiometabolic diseases except coronary artery disease were more prevalent among those with food insecurity. Food insecurity increased over time and was more frequent for patients with CVD but not for cardiometabolic risk factors. From 2011 to 2018, non-Hispanic Black adults with CVD had a decrease in food insecurity prevalence (36.6%; 95% CI, 23.9%-49.4%, to 25.4%; 95% CI, 21.4%-29.3%; P = .04 for trend), whereas adults of other races and ethnicities or data based on cardiometabolic risk factors had no significant change. For individuals who had food insecurity, SNAP participation was higher among those with CVD vs without CVD (54.2%; 95% CI, 46.6%-61.8%, vs 44.3%; 95% CI, 40.5%-48.1%; P = .01).

Conclusions:
and relevance
The prevalence of food insecurity among patients with CVD increased over time. Although members of non-Hispanic Black and Hispanic groups had the highest food insecurity, non-Hispanic Black individuals with CVD were the only group to have a significant decrease in food insecurity since 2011. Increased recognition of food insecurity and resources for treating it are needed to address the negative consequences of food insecurity on CVD outcomes.



JAMA Cardiol: 28 Sep 2022; epub ahead of print
Brandt EJ, Chang T, Leung C, Ayanian JZ, Nallamothu BK
JAMA Cardiol: 28 Sep 2022; epub ahead of print | PMID: 36170056
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Impact:
Abstract

Long-term Effects of P2Y12 Inhibitor Monotherapy After Percutaneous Coronary Intervention: 3-Year Follow-up of the SMART-CHOICE Randomized Clinical Trial.

Choi KH, Park YH, Song YB, Park TK, ... Hahn JY, SMART-CHOICE Investigators
Importance
Although P2Y12 inhibitor monotherapy after a minimum period of dual antiplatelet therapy (DAPT) is a well-known way to reduce the risk of bleeding after percutaneous coronary intervention (PCI), data comparing long-term clinical outcomes between P2Y12 inhibitor monotherapy and extended DAPT in patients undergoing PCI have been unavailable.
Objective
To identify the long-term safety and efficacy of P2Y12 inhibitor monotherapy following 3 months of DAPT after PCI.
Design, setting, and participants
The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Monotherapy and Dual Antiplatelet Therapy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE) trial was an open-label, noninferiority, randomized clinical trial, enrolling patients who underwent PCI with drug-eluting stent at 33 hospitals in Korea from March 2014 through July 2017. Clinical follow-up was extended to 3 years and completed in August 2020.
Interventions
Patients were randomly assigned to either P2Y12 inhibitor monotherapy after 3 months of DAPT or DAPT for 12 months or longer.
Main outcomes and measures
The primary end point was major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) at 3 years. The secondary end points included the components of the primary end point, bleeding (defined as Bleeding Academic Research Consortium [BARC] types 2-5), and major bleeding (BARC types 3-5).
Results
In total, 2993 patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (1495 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1087 [72.7%] male) or prolonged DAPT (1498 patients [50%]; mean [SD] age, 64.6 [10.7] years; 1111 [74.2%] male) after PCI. At 3 years, the primary end point occurred in 87 individuals (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR], 1.06 [95% CI, 0.79-1.44]; P = .69). P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding (BARC types 2-5: 112 [3.2%] vs 44 [8.2%]; HR, 0.39 [95% CI, 0.28-0.55]; P < .001) and major bleeding (BARC types 3-5; 17 [1.2%] vs 31 [2.4%]; HR, 0.56 [95% CI, 0.31-0.99]; P = .048), compared with prolonged DAPT. The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.

Conclusions:
and relevance
Among patients who underwent PCI and completed 3-month DAPT, P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged DAPT. Although the 3-year risk of ischemic cardiovascular events was comparable between the 2 groups, this result should be interpreted with caution owing to the limited number of events and sample size.
Trial registration
ClinicalTrials.gov Identifier: NCT02079194.



JAMA Cardiol: 28 Sep 2022; epub ahead of print
Choi KH, Park YH, Song YB, Park TK, ... Hahn JY, SMART-CHOICE Investigators
JAMA Cardiol: 28 Sep 2022; epub ahead of print | PMID: 36169938
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Impact:
Abstract

Measured Blood Pressure, Genetically Predicted Blood Pressure, and Cardiovascular Disease Risk in the UK Biobank.

Cho SMJ, Koyama S, Ruan Y, Lannery K, ... Honigberg MC, Natarajan P
Importance
Hypertension remains the major cardiovascular disease risk factor globally, but variability in measured blood pressure may result in suboptimal management. Whether genetic contributors to elevated blood pressure may complementarily inform cardiovascular disease risk assessment is unknown.
Objective
To examine incident cardiovascular disease by blood pressure polygenic risk score independent of measured blood pressures and antihypertensive medication prescriptions.
Design, setting, and participants
The cohort study (UK Biobank) recruited UK residents aged 40 to 69 years between March 2006 and August 2010. Participants without a prior physician diagnosis of cardiovascular disease, including myocardial infarction, stroke, or heart failure, were included. Excluded were individuals with mismatch between self-reported and genotypically inferred sex, sex aneuploidy, missing genotype rates of 1% or greater, and excess genotypic heterozygosity. Data analyses were performed from September 25, 2021, to July 21, 2022.
Exposures
Measured blood pressure and externally derived blood pressure polygenic risk score stratified by hypertension diagnosis and management, which included normal blood pressure (<130/80 mm Hg without antihypertensives), untreated hypertension (systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg without antihypertensives), and treated hypertension (current antihypertensives prescriptions).
Main outcomes and measures
Composite of first incident myocardial infarction, stroke, heart failure, or cardiovascular-related death.
Results
Of the 331 078 study participants included (mean [SD] age at enrollment, 56.9 [8.1] years; 178 824 female [54.0%]), 83 094 (25.1%) had normal blood pressure, 197 597 (59.7%) had untreated hypertension, and 50 387 (15.2%) had treated hypertension. Over a median (IQR) follow-up of 11.1 (10.4-11.8) years, the primary outcome occurred in 15 293 participants. Among those with normal blood pressure, untreated hypertension, and treated hypertension, each SD increase in measured systolic blood pressure was associated with hazard ratios of 1.08 (95% CI, 0.93-1.25), 1.20 (95% CI, 1.16-1.23), and 1.16 (95% CI, 1.11-1.20), respectively, for the primary outcome. Among these same categories, each SD increase in genetically predicted systolic blood pressure was associated with increased hazard ratios of 1.13 (95% CI, 1.05-1.20), 1.04 (95% CI, 1.01-1.07), and 1.06 (95% CI, 1.02-1.10), respectively, for the primary outcome independent of measured blood pressures and other covariates. Findings were similar for measured and genetically predicted diastolic blood pressure.

Conclusions:
and relevance
Blood pressure polygenic risk score may augment identification of individuals at heightened cardiovascular risk, including those with both normal blood pressure and hypertension. Whether it may also guide antihypertensive initiation or intensification requires further study.



JAMA Cardiol: 28 Sep 2022; epub ahead of print
Cho SMJ, Koyama S, Ruan Y, Lannery K, ... Honigberg MC, Natarajan P
JAMA Cardiol: 28 Sep 2022; epub ahead of print | PMID: 36169945
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Impact:
Abstract

Association of Donors With US Public Health Service Risk Criteria and Outcomes After Adult vs Pediatric Cardiac Transplant.

Burstein DS, Rossano JW, Lindenfeld J, Schlendorf KH, ... Scholl SR, Menachem JN
Importance
The United Network for Organ Sharing (UNOS) evaluates donor risk for acute transmission of HIV, hepatitis B, or hepatitis C based on US Public Health Services (PHS)-specific criteria. However, recent data regarding use and outcomes of those donors with PHS risk criteria among pediatric and adult heart transplant recipients are lacking.
Objective
To compare use and outcomes of graft from donors with PHS risk criteria vs those with a standard-risk donor (SRD) in children vs adults in a contemporary cohort.
Design, setting, and participants
This cohort was a nationwide analysis of heart transplants in the US that used data from the UNOS database. Participants were children (<18 years old) and adults (≥18 years old) who received a heart transplant from January 1, 2010, to December 31, 2021.
Exposures
UNOS-defined donor risk status.
Main outcomes and measures
Trend analysis compared changes in PHS risk criteria use among children and adults. Patient survival was analyzed using Kaplan-Meier curves with log rank and Cox proportional hazards to compare PHS risk-criteria outcomes vs SRD-criteria outcomes in children and adult heart transplant recipients. Additional analysis was performed among adults who received a PHS-risk criteria graft that was previously declined for pediatric recipients.
Results
Of 5115 pediatric transplant recipients (donor without PHS risk median [IQR] age, 5 [0-13] years and donor with PHS risk median [IQR] age, 8 [0-14] years) and 30 289 adult heart transplant recipients (donor without PHS risk median [IQR] age, 56 [46-63] years and donor with PHS risk median [IQR] age, 57 [47-63] years), PHS risk criteria comprised 8% in children vs 25% in adults. PHS criteria are being increasingly used over the past decade with the proportion of recipients transplanted with PHS risk-criteria donors being approximately 3 times greater among adult recipients than children recipients. Pediatric recipients of a PHS risk-criteria donor had greater pretransplant ventilatory support, whereas adult recipients of a PHS risk-criteria donor had greater pretransplant extracorporeal membrane oxygenation use. Patient survival was similar between pediatric recipients of PHS risk-criteria grafts vs SRD-criteria grafts and slightly higher among adult recipients of PHS risk-criteria grafts vs SRD-criteria grafts. The 1778 adult recipients who received a PHS criteria-risk donor that was previously declined for pediatric recipients had similar patient survival recipients compared with SRD-criteria donors (HR, 0.92; 95% CI, 0.81-1.03; P = .18).

Conclusions:
and relevance
In the current era, a 3-fold greater proportion of adult recipients receive a PHS risk-criteria graft compared with children despite similar posttransplant patient survival. The ongoing organ donor shortage underscores the need for consideration of PHS risk criteria where these donors remain underused.



JAMA Cardiol: 21 Sep 2022; epub ahead of print
Burstein DS, Rossano JW, Lindenfeld J, Schlendorf KH, ... Scholl SR, Menachem JN
JAMA Cardiol: 21 Sep 2022; epub ahead of print | PMID: 36129691
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Impact:
Abstract

Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure: A Secondary Analysis of EMPEROR-Pooled.

Ferreira JP, Zannad F, Butler J, Filippatos G, ... Anker SD, Packer M
Importance
Albuminuria, routinely assessed as spot urine albumin-to-creatinine ratio (UACR), indicates structural damage of the glomerular filtration barrier and is associated with poor kidney and cardiovascular outcomes. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce UACR in patients with type 2 diabetes, but its use in patients with heart failure (HF) is less well studied.
Objective
To analyze the association of empagliflozin with study outcomes across baseline levels of albuminuria and change in albuminuria in patients with HF across a wide range of ejection fraction levels.
Design, setting, and participants
This post hoc analysis included all patients with HF from the EMPEROR-Pooled analysis using combined individual patient data from the international multicenter randomized double-blind parallel-group, placebo-controlled EMPEROR-Reduced and EMPEROR-Preserved trials. Participants in the original trials were excluded from this analysis if they were missing baseline UACR data. EMPEROR-Preserved was conducted from March 27, 2017, to April 26, 2021, and EMPEROR-Reduced was conducted from April 6, 2017, to May 28, 2020. Data were analyzed from January to June 2022.
Interventions
Randomization to empagliflozin or placebo.
Main outcomes and measures
New-onset macroalbuminuria and regression to normoalbuminuria and microalbuminuria.
Results
A total of 9673 patients were included (mean [SD] age, 69.9 [10.4] years; 3551 [36.7%] female and 6122 [63.3%] male). Of these, 5552 patients had normoalbuminuria (UACR <30 mg/g) and 1025 had macroalbuminuria (UACR >300 mg/g). Compared with normoalbuminuria, macroalbuminuria was associated with younger age, races other than White, obesity, male sex, site region other than Europe, higher levels of N-terminal pro-hormone brain natriuretic peptide and high-sensitivity troponin T, higher blood pressure, higher New York Heart Association class, greater HF duration, more frequent previous HF hospitalizations, diabetes, hypertension, lower eGFR, and less frequent use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and mineralocorticoid receptor antagonists. An increase in events was observed in individuals with higher UACR levels. The association of empagliflozin with cardiovascular mortality or HF hospitalization was consistent across UACR categories (hazard ratio [HR], 0.80; 95% CI, 0.69-0.92 for normoalbuminuria; HR, 0.74; 95% CI, 0.63-0.86 for microalbuminuria; HR, 0.78; 95% CI, 0.63-0.98 for macroalbuminuria; interaction P trend = .71). Treatment with empagliflozin was associated with lower incidence of new macroalbuminuria (HR, 0.81; 95% CI, 0.70-0.94; P = .005) and an increase in rate of remission to sustained normoalbuminuria or microalbuminuria (HR, 1.31; 95% CI, 1.07-1.59; P = .009) but not with a reduction in UACR in the overall population; however, UACR was reduced in patients with diabetes, who had higher UACR levels than patients without diabetes (geometric mean for diabetes at baseline, 0.91; 95% CI, 0.85-0.98 and for no diabetes at baseline, 1.08; 95% CI, 1.01-1.16; interaction P = .008).

Conclusions:
and relevance
In this post hoc analysis of a randomized clinical trial, compared with placebo, empagliflozin was associated with reduced HF hospitalizations or cardiovascular death irrespective of albuminuria levels at baseline, reduced progression to macroalbuminuria, and reversion of macroalbuminuria.
Trial registration
ClinicalTrials.gov Identifiers: NCT03057977 and NCT03057951.



JAMA Cardiol: 21 Sep 2022; epub ahead of print
Ferreira JP, Zannad F, Butler J, Filippatos G, ... Anker SD, Packer M
JAMA Cardiol: 21 Sep 2022; epub ahead of print | PMID: 36129693
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Impact:
Abstract

Complete Revascularization vs Culprit Lesion-Only Percutaneous Coronary Intervention for Angina-Related Quality of Life in Patients With ST-Segment Elevation Myocardial Infarction: Results From the COMPLETE Randomized Clinical Trial.

Mehta SR, Wang J, Wood DA, Spertus JA, ... Cairns JA, COMPLETE Trial Investigators
Importance
In patients with multivessel coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI), complete revascularization reduces major cardiovascular events compared with culprit lesion-only percutaneous coronary intervention (PCI). Whether complete revascularization also improves angina-related health status is unknown.
Objective
To determine whether complete revascularization improves angina status in patients with STEMI and multivessel CAD.
Design, setting, and participants
This secondary analysis of a randomized, multinational, open label trial of patient-reported outcomes took place in 140 primary PCI centers in 31 countries. Patients presenting with STEMI and multivessel CAD were randomized between February 1, 2013, and March 6, 2017. Analysis took place between July 2021 and December 2021.
Interventions
Following PCI of the culprit lesion, patients with STEMI and multivessel CAD were randomized to receive either complete revascularization with additional PCI of angiographically significant nonculprit lesions or to no further revascularization.
Main outcomes and measures
Seattle Angina Questionnaire Angina Frequency (SAQ-AF) score (range, 0 [daily angina] to 100 [no angina]) and the proportion of angina-free individuals by study end.
Results
Of 4041 patients, 2016 were randomized to complete revascularization and 2025 to culprit lesion-only PCI. The mean (SD) age of patients was 62 (10.7) years, and 3225 (80%) were male. The mean (SD) SAQ-AF score increased from 87.1 (17.8) points at baseline to 97.1 (9.7) points at a median follow-up of 3 years in the complete revascularization group (score change, 9.9 [95% CI, 9.0-10.8]; P < .001) compared with an increase of 87.2 (18.4) to 96.3 (10.9) points (score change, 8.9 [95% CI, 8.0-9.8]; P < .001) in the culprit lesion-only group (between-group difference, 0.97 points [95% CI, 0.27-1.67]; P = .006). Overall, 1457 patients (87.5%) were free of angina (SAQ-AF score, 100) in the complete revascularization group compared with 1376 patients (84.3%) in the culprit lesion-only group (absolute difference, 3.2% [95% CI, 0.7%-5.7%]; P = .01). This benefit was observed mainly in patients with nonculprit lesion stenosis severity of 80% or more (absolute difference, 4.7%; interaction P = .02).

Conclusions:
and relevance
In patients with STEMI and multivessel CAD, complete revascularization resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion-only strategy. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.



JAMA Cardiol: 21 Sep 2022; epub ahead of print
Mehta SR, Wang J, Wood DA, Spertus JA, ... Cairns JA, COMPLETE Trial Investigators
JAMA Cardiol: 21 Sep 2022; epub ahead of print | PMID: 36129696
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Impact:
Abstract

Routine Ultrasonography Guidance for Femoral Vascular Access for Cardiac Procedures: The UNIVERSAL Randomized Clinical Trial.

Jolly SS, AlRashidi S, d\'Entremont MA, Alansari O, ... Dutra G, Winter J
Importance
A significant limitation of femoral artery access for cardiac interventions is the increased risk of vascular complications and bleeding compared with radial access. Strategies to make femoral access safer are needed.
Objective
To determine whether routinely using ultrasonography guidance for femoral arterial access for coronary angiography/intervention reduces bleeding or vascular complications.
Design, setting, and participants
The Routine Ultrasound Guidance for Vascular Access for Cardiac Procedures (UNIVERSAL) randomized clinical trial is a multicenter, prospective, open-label trial of ultrasonography-guided femoral access vs no ultrasonography for coronary angiography or intervention with planned femoral access. Patients were randomized from June 26, 2018, to April 26, 2022. Patients with ST-elevation myocardial infarction were not eligible.
Interventions
Ultrasonography guidance vs no ultrasonography guidance for femoral arterial access on a background of fluoroscopic landmarking.
Main outcomes and measures
The primary composite outcome is the composite of major bleeding based on the Bleeding Academic Research Consortium 2, 3, or 5 criteria or major vascular complications within 30 days.
Results
A total of 621 patients were randomized at 2 centers in Canada (mean [SD] age, 71 [10.24] years; 158 [25.4%] female). The primary outcome occurred in 40 of 311 patients (12.9%) in the ultrasonography group vs 50 of 310 patients (16.1%) without ultrasonography (odds ratio, 0.77 [95% CI, 0.49-1.20]; P = .25). The rates of Bleeding Academic Research Consortium 2, 3, or 5 bleeding were 10.0% (31 of 311) vs 10.7% (33 of 310) (odds ratio, 0.93 [95% CI, 0.55-1.56]; P = .78). The rates of major vascular complications were 6.4% (20 of 311) vs 9.4% (29 of 310) (odds ratio, 0.67 [95% CI, 0.37-1.20]; P = .18). Ultrasonography improved first-pass success (277 of 311 [86.6%] vs 222 of 310 [70.0%]; odds ratio, 2.76 [95% CI, 1.85-4.12]; P < .001) and reduced the number of arterial puncture attempts (mean [SD], 1.2 [0.5] vs 1.4 [0.8]; mean difference, -0.26 [95% CI, -0.37 to -0.16]; P < .001) and venipuncture (10 of 311 [3.1%] vs 37 of 310 [11.7%]; odds ratio, 0.24 [95% CI, 0.12-0.50]; P < .001) with similar times to access (mean [SD], 114 [185] vs 129 [206] seconds; mean difference, -15.1 [95% CI, -45.9 to 15.8]; P = .34). All prerandomization prespecified subgroups were consistent with the overall finding.

Conclusions:
and relevance
In this randomized clinical trial, use of ultrasonography for femoral access did not reduce bleeding or vascular complications. However, ultrasonography did reduce the risk of venipuncture and number of attempts. Larger trials may be required to demonstrate additional potential benefits of ultrasonography-guided access.
Trial registration
ClinicalTrials.gov Identifier: NCT03537118.



JAMA Cardiol: 18 Sep 2022; epub ahead of print
Jolly SS, AlRashidi S, d'Entremont MA, Alansari O, ... Dutra G, Winter J
JAMA Cardiol: 18 Sep 2022; epub ahead of print | PMID: 36116089
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Impact:
Abstract

Burden of Rare Genetic Variants in Spontaneous Coronary Artery Dissection With High-risk Features.

Wang Y, Starovoytov A, Murad AM, Hunker KL, ... Saw J, Ganesh SK
Importance
The emerging genetic basis of spontaneous coronary artery dissection (SCAD) has been defined as both partially complex and monogenic in some patients, involving variants predominantly in genes known to underlie vascular connective tissue diseases (CTDs). The effect of these genetic influences has not been defined in high-risk SCAD phenotypes, and the identification of a high-risk subgroup of individuals may help to guide clinical genetic evaluations of SCAD.
Objective
To identify and quantify the burden of rare genetic variation in individuals with SCAD with high-risk clinical features.
Design, setting, and participants
Whole-exome sequencing (WES) was performed for subsequent case-control association analyses and individual variant annotation among individuals with high-risk SCAD. Genetic variants were annotated for pathogenicity by in-silico analysis of genes previously defined by sequencing for vascular CTDs and/or SCAD, as well as genes prioritized by genome-wide association study (GWAS) and colocalization of arterial expression quantitative trait loci. Unbiased genome-wide association analysis of the WES data was performed by comparing aggregated variants in individuals with SCAD to healthy matched controls or the Genome Aggregation Database (gnomAD). This study was conducted at a tertiary care center. Individuals in the Canadian SCAD Registry genetics study with a high-risk SCAD phenotype were selected and defined as peripartum SCAD, recurrent SCAD, or SCAD in an individual with family history of arteriopathy.
Main outcomes and measures
Burden of genetic variants defined by DNA sequencing in individuals with high-risk SCAD.
Results
This study included a total of 336 participants (mean [SD] age, 53.0 [9.5] years; 301 female participants [90%]). Variants in vascular CTD genes were identified in 17.0% of individuals (16 of 94) with high-risk SCAD and were enriched (OR, 2.6; 95% CI, 1.6-4.2; P = 7.8 × 10-4) as compared with gnomAD, with leading significant signals in COL3A1 (OR, 13.4; 95% CI, 4.9-36.2; P = 2.8 × 10-4) and Loeys-Dietz syndrome genes (OR, 7.9; 95% CI, 2.9-21.2; P = 2.0 × 10-3). Variants in GWAS-prioritized genes, observed in 6.4% of individuals (6 of 94) with high-risk SCAD, were also enriched (OR, 3.6; 95% CI, 1.6-8.2; P = 7.4 × 10-3). Variants annotated as likely pathogenic or pathogenic occurred in 4 individuals, in the COL3A1, TGFBR2, and ADAMTSL4 genes. Genome-wide aggregated variant testing identified novel associations with peripartum SCAD.

Conclusions:
and relevance
In this genetic study, approximately 1 in 5 individuals with a high-risk SCAD phenotype harbored a rare genetic variant in genes currently implicated for SCAD. Genetic screening in this subgroup of individuals presenting with SCAD may be considered.



JAMA Cardiol: 14 Sep 2022; epub ahead of print
Wang Y, Starovoytov A, Murad AM, Hunker KL, ... Saw J, Ganesh SK
JAMA Cardiol: 14 Sep 2022; epub ahead of print | PMID: 36103205
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Impact:
Abstract

Cardiovascular Magnetic Resonance Imaging Phenotypes and Long-term Outcomes in Patients With Suspected Cardiac Sarcoidosis.

Athwal PSS, Chhikara S, Ismail MF, Ismail K, ... Perlman D, Shenoy C
Importance
In patients with sarcoidosis with suspected cardiac involvement, late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging (CMR) identifies those with an increased risk of adverse outcomes. However, these outcomes are experienced by only a minority of patients with LGE, and identifying this subgroup may improve treatment and outcomes in these patients.
Objective
To assess whether CMR phenotypes based on left ventricular ejection fraction (LVEF) and LGE in patients with suspected cardiac sarcoidosis (CS) are associated with adverse outcomes during follow-up.
Design, setting, and participants
This cohort study included consecutive patients with histologically proven sarcoidosis who underwent CMR for the evaluation of suspected CS from 2004 to 2020 with a median follow-up of 4.3 years at an academic medical center in Minnesota. Demographic data, medical history, comorbidities, medications, and outcome data were collected blinded to CMR data.
Exposures
CMR phenotypes were identified based on LVEF and LGE presence and features. LGE was classified as pathology-frequent or pathology-rare based on the frequency of cardiac damage features on gross pathology assessment of the hearts of patients with CS who had sudden cardiac death or cardiac transplant.
Main outcomes and measures
Composite of ventricular arrhythmic events and composite of heart failure events.
Results
Among 504 patients (mean [SD] age, 54.1 [12.5] years; 242 [48.0%] female and 262 [52.0%] male; 2 [0.4%] American Indian or Alaska Native, 6 [1.2%] Asian, 90 [17.9%] Black or African American, 399 [79.2%] White, 5 [1.0%] of 2 or more races (including the above-mentioned categories and Native Hawaiian or Other Pacific Islander), and 2 [0.4%] of unknown race; 4 [0.8%] Hispanic or Latino, 498 [98.8%] not Hispanic or Latino, and 2 [0.4%] of unknown ethnicity), 4 distinct CMR phenotypes were identified: normal LVEF and no LGE (n = 290; 57.5%), abnormal LVEF and no LGE (n = 53; 10.5%), pathology-frequent LGE (n = 103; 20.4%), and pathology-rare LGE (n = 58; 11.5%). The phenotype with pathology-frequent LGE was associated with a high risk of arrhythmic events (hazard ratio [HR], 12.12; 95% CI, 3.62-40.57; P < .001) independent of LVEF and extent of left ventricular late gadolinium enhancement (LVLGE). It was also associated with a high risk of heart failure events (HR, 2.49; 95% CI, 1.19-5.22; P = .02) independent of age, pulmonary hypertension, LVEF, right ventricular ejection fraction, and LVLGE extent. Risk of arrhythmic events was greater with an increasing number of pathology-frequent LGE features. The absence of the pathology-frequent LGE phenotype was associated with a low risk of arrhythmic events, even in the presence of LGE or abnormal LVEF.

Conclusions:
and relevance
This cohort study found that a CMR phenotype involving pathology-frequent LGE features was associated with a high risk of arrhythmic and heart failure events in patients with sarcoidosis. The findings indicate that CMR phenotypes could be used to optimize clinical decision-making for treatment options, such as implantable cardioverter-defibrillators.



JAMA Cardiol: 14 Sep 2022; epub ahead of print
Athwal PSS, Chhikara S, Ismail MF, Ismail K, ... Perlman D, Shenoy C
JAMA Cardiol: 14 Sep 2022; epub ahead of print | PMID: 36103165
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Impact:
Abstract

A Simple Score to Identify Increased Risk of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction.

Davies DR, Redfield MM, Scott CG, Minamisawa M, ... Borlaug BA, AbouEzzeddine OF
Importance
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a form of heart failure (HF) with preserved ejection fraction (HFpEF). Technetium Tc 99m pyrophosphate scintigraphy (PYP) enables ATTR-CM diagnosis. It is unclear which patients with HFpEF have sufficient risk of ATTR-CM to warrant PYP.
Objective
To derive and validate a simple ATTR-CM score to predict increased risk of ATTR-CM in patients with HFpEF.
Design, setting, and participants
Retrospective cohort study of 666 patients with HF (ejection fraction ≥ 40%) and suspected ATTR-CM referred for PYP at Mayo Clinic, Rochester, Minnesota, from May 10, 2013, through August 31, 2020. These data were analyzed September 2020 through December 2020. A logistic regression model predictive of ATTR-CM was derived and converted to a point-based ATTR-CM risk score. The score was further validated in a community ATTR-CM epidemiology study of older patients with HFpEF with increased left ventricular wall thickness ([WT] ≥ 12 mm) and in an external (Northwestern University, Chicago, Illinois) HFpEF cohort referred for PYP. Race was self-reported by the participants. In all cohorts, both case patients and control patients were definitively ascertained by PYP scanning and specialist evaluation.
Main outcomes and measures
Performance of the derived ATTR-CM score in all cohorts (referral validation, community validation, and external validation) and prevalence of a high-risk ATTR-CM score in 4 multinational HFpEF clinical trials.
Results
Participant cohorts included were referral derivation (n = 416; 13 participants [3%] were Black and 380 participants [94%] were White; ATTR-CM prevalence = 45%), referral validation (n = 250; 12 participants [5%]were Black and 228 participants [93%] were White; ATTR-CM prevalence = 48% ), community validation (n = 286; 5 participants [2%] were Black and 275 participants [96%] were White; ATTR-CM prevalence = 6% ), and external validation (n = 66; 23 participants [37%] were Black and 36 participants [58%] were White; ATTR-CM prevalence = 39%). Score variables included age, male sex, hypertension diagnosis, relative WT more than 0.57, posterior WT of 12 mm or more, and ejection fraction less than 60% (score range -1 to 10). Discrimination (area under the receiver operating characteristic curve [AUC] 0.89; 95% CI, 0.86-0.92; P < .001) and calibration (Hosmer-Lemeshow; χ2 = 4.6; P = .46) were strong. Discrimination (AUC ≥ 0.84; P < .001 for all) and calibration (Hosmer-Lemeshow χ2  = 2.8; P = .84; Hosmer-Lemeshow χ2  = 4.4; P = .35; Hosmer-Lemeshow χ2 = 2.5; P = .78 in referral, community, and external validation cohorts, respectively) were maintained in all validation cohorts. Precision-recall curves and predictive value vs prevalence plots indicated clinically useful classification performance for a score of 6 or more (positive predictive value ≥25%) in clinically relevant ATTR-CM prevalence (≥10% of patients with HFpEF) scenarios. In the HFpEF clinical trials, 11% to 35% of male and 0% to 6% of female patients had a high-risk (≥6) ATTR-CM score.

Conclusions:
and relevance
A simple 6 variable clinical score may be used to guide use of PYP and increase recognition of ATTR-CM among patients with HFpEF in the community. Further validation in larger and more diverse populations is needed.



JAMA Cardiol: 07 Sep 2022; epub ahead of print
Davies DR, Redfield MM, Scott CG, Minamisawa M, ... Borlaug BA, AbouEzzeddine OF
JAMA Cardiol: 07 Sep 2022; epub ahead of print | PMID: 36069809
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Impact:
Abstract

Characteristics, Process Metrics, and Outcomes Among Patients With ST-Elevation Myocardial Infarction in Rural vs Urban Areas in the US: A Report From the US National Cardiovascular Data Registry.

Hillerson D, Li S, Misumida N, Wegermann ZK, ... Wang TY, Ziada KM
Importance
Patients with ST-segment elevation myocardial infarction (STEMI) living in rural settings often have worse clinical outcomes compared with their urban counterparts. Whether this discrepancy is due to clinical characteristics or delays in timely reperfusion with primary percutaneous coronary intervention (PPCI) or fibrinolysis is unclear.
Objective
To assess process metrics and outcomes among patients with STEMI in rural and urban settings across the US.
Design, setting, and participants
This cross-sectional multicenter study analyzed data for 70 424 adult patients with STEMI from the National Cardiovascular Data Registry Chest Pain-MI Registry in 686 participating US hospitals between January 1, 2019, and June 30, 2020. Patients without a valid zip code were excluded, and those transferred to a different hospital during the course of the study were excluded from outcome analysis.
Main outcomes and measures
In-hospital mortality and time-to-reperfusion metrics.
Results
This study included 70 424 patients with STEMI (median [IQR] age, 63 [54-73] years; 49 850 [70.8%] male and 20 574 [29.2%] female; patient self-reported race: 6753 [9.6%] Black, 60 114 [85.4%] White, and 2096 [3.0%] of another race [including American Indian, Alaskan Native, Native Hawaiian, and Pacific Islander]; 5281 [7.5%] individuals of Hispanic or Latino ethnicity) in 686 hospitals (50 702 [72.0%] living in urban zip codes and 19 722 [28.0%] in rural zip codes). Patients from rural settings were less likely to undergo PPCI compared with patients from urban settings (14 443 [73.2%] vs 43 142 [85.1%], respectively; P < .001) and more often received fibrinolytics (2848 [19.7%] vs 937 [2.7%]; P < .001). Compared with patients from urban settings, those in rural settings undergoing PPCI had longer median (IQR) time from first medical contact to catheterization laboratory activation (30 [12-42] minutes vs 22 [15-59] minutes; P < .001) and longer median (IQR) time from first medical contact to device (99 minutes [75-131] vs 81 [66-103] minutes; P < .001), including those who arrived directly at PPCI centers (83 [66-107] minutes vs 78 [64-97] minutes; P < .001) and those who transferred to PPCI centers from another treatment center (125 [102-163] minutes vs 103 [85-135] minutes; P < .001). Among those who transferred in, median (IQR) door-in-door-out time was longer in patients from rural settings (63 [41-100] minutes vs 50 [35-80] minutes; P < .001). Out-of-hospital cardiac arrest was more common in patients from urban vs rural settings (3099 [6.1%] vs 958 [4.9%]; P < .001), and patients from urban settings were more likely to present with heart failure (4112 [8.1%] vs 1314 [6.7%]; P < .001). After multivariable adjustment, there was no significant difference in in-hospital mortality between rural and urban groups (adjusted odds ratio, 0.97; 95% CI, 0.89-1.06).

Conclusions:
and relevance
In this large cohort of patients with STEMI from US hospitals participating in the National Cardiovascular Data Registry Chest Pain-MI Registry, patients living in rural settings had longer times to reperfusion, were less likely to receive PPCI or meet guideline-recommended time to reperfusion, and more frequently received fibrinolytics than patients living in urban settings. However, there was no difference in adjusted in-hospital mortality between patients with STEMI from urban and rural settings.



JAMA Cardiol: 31 Aug 2022; epub ahead of print
Hillerson D, Li S, Misumida N, Wegermann ZK, ... Wang TY, Ziada KM
JAMA Cardiol: 31 Aug 2022; epub ahead of print | PMID: 36044196
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Impact:
Abstract

Sex Differences in Atrial Fibrillation Risk: The VITAL Rhythm Study.

Siddiqi HK, Vinayagamoorthy M, Gencer B, Ng C, ... Manson JE, Albert CM
Importance
Women have a lower incidence of atrial fibrillation (AF) compared with men in several studies, but it is unclear whether this sex difference is independent of sex differences in prevalent cardiovascular disease (CVD), body size, and other risk factors.
Objective
To examine sex differences in AF incidence and whether AF risk factors differ by sex in a contemporary cohort of men and women without prevalent CVD.
Design, setting, and participants
This was a prospective cohort analysis within the Vitamin D and Omega-3 Trial (VITAL) Rhythm Study, a randomized trial that examined the effect of vitamin D and ω-3 fatty acid supplementation on incident AF among men 50 years or older and women 55 years or older without a prior history of prevalent AF, CVD, or cancer at baseline. Data were analyzed from September 29, 2020, to June 29, 2021.
Exposures
Sex, height, weight, body mass index (BMI), body surface area (BSA), and other AF risk factors at study enrollment.
Main outcomes and measures
Incident AF confirmed by medical record review.
Results
A total of 25 119 individuals (mean [SD] age, 67.0 [7.1] years; 12 757 women [51%]) were included in this study. Over a median (IQR) follow-up of 5.3 (5.1-5.7) years, 900 confirmed incident AF events occurred among 12 362 men (495 events, 4.0%) and 12 757 women (405 events, 3.2%). After adjustment for age and treatment assignment, women were at lower risk for incident AF than men (hazard ratio [HR], 0.68; 95% CI, 0.59-0.77; P < .001). The inverse association between female sex and AF persisted after adjustment for race and ethnicity, smoking, alcohol intake, hypertension, diabetes (type 1, type 2, gestational), thyroid disease, exercise, and BMI (HR, 0.73; 95% CI, 0.63-0.85; P <.001). However, female sex was positively associated with AF when height (HR, 1.39; 95% CI, 1.14-1.72; P = .001), height and weight (HR 1.49, 95% CI, 1.21-1.82; P <.001), or BSA (HR, 1.25; 95% CI, 1.06-1.49; P = .009) were substituted for BMI in the multivariate model. In stratified models, risk factor associations with incident AF were similar for women and men.

Conclusions:
and relevance
In this cohort study, findings suggest that after controlling for height and/or body size, women without CVD at baseline were at higher risk for AF than men, suggesting that sex differences in body size account for much of the protective association between female sex and AF. These data underscore the importance of AF prevention in women.



JAMA Cardiol: 31 Aug 2022; epub ahead of print
Siddiqi HK, Vinayagamoorthy M, Gencer B, Ng C, ... Manson JE, Albert CM
JAMA Cardiol: 31 Aug 2022; epub ahead of print | PMID: 36044209
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Impact:
Abstract

Evaluating the Application of Chronic Heart Failure Therapies and Developing Treatments in Individuals With Recent Myocardial Infarction: A Review.

Harrington J, Petrie MC, Anker SD, Bhatt DL, ... Hernandez AF, Butler J
Importance
Despite advances in cardiac care, patients remain at a high risk of death and the development of heart failure (HF) following myocardial infarction (MI). These risks are highest in patients with reduced ejection fraction (EF) or signs of HF immediately after MI. Drugs to mitigate these risks have been identified through the systematic evaluation of therapies with proven efficacy in patients with HF and reduced EF (HFrEF).
Observations
Although landmark studies in patients with HFrEF consistently exclude patients with recent MI, dedicated post-MI trials of these drugs have led to multiple therapies with proven benefit in these patients. However, not all therapies with proven efficacy in patients with chronic HF have been shown to provide benefit in the post-MI population, as recently evidenced by the discrepant results between chronic HF and post-MI trials of sacubitril-valsartan. Similarly, multiple trials of early and aggressive use of therapies effective in chronic heart failure immediately post-MI failed to demonstrate benefit or were associated with harm, emphasizing the vulnerability of the post-MI population.

Conclusions:
and relevance
Trials of patients at high risk of HF following MI have emphasized the differences between the post-MI and HFrEF populations and the necessity for dedicated trials in the post-MI population. This review summarizes trials studying the use of these therapies for at-risk patients following MI from therapies used in patients with HFrEF and exploring new potential therapies for this high-risk population.



JAMA Cardiol: 31 Aug 2022; epub ahead of print
Harrington J, Petrie MC, Anker SD, Bhatt DL, ... Hernandez AF, Butler J
JAMA Cardiol: 31 Aug 2022; epub ahead of print | PMID: 36044233
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Impact:
Abstract

Early Mortality in Type A Acute Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection.

Harris KM, Nienaber CA, Peterson MD, Woznicki EM, ... Isselbacher EM, Eagle KA
Importance
Early data revealed a mortality rate of 1% to 2% per hour for type A acute aortic dissection (TAAAD) during the initial 48 hours. Despite advances in diagnostic testing and treatment, this mortality rate continues to be cited because of a lack of contemporary data characterizing early mortality and the effect of timely surgery.
Objective
To examine early mortality rates for patients with TAAAD in the contemporary era.
Design, setting, and participants
This cohort study examined data for patients with TAAAD in the International Registry of Acute Aortic Dissection between 1996 and 2018. Patients were grouped according to the mode of their intended treatment, surgical or medical.
Exposure
Surgical treatment.
Main outcomes and measures
Mortality was assessed in the initial 48 hours after hospital arrival using Kaplan-Meier curves. In-hospital complications were also evaluated.
Results
A total of 5611 patients with TAAAD were identified based on intended treatment: 5131 (91.4%) in the surgical group (3442 [67.1%] male; mean [SD] age, 60.4 [14.1] years) and 480 (8.6%) in the medical group (480 [52.5%] male; mean [SD] age, 70.9 [14.7] years). Reasons for medical management included advanced age (n = 141), comorbidities (n = 281), and patient preference (n = 81). Over the first 48 hours, the mortality for all patients in the study was 5.8%. Among patients who were medically managed, mortality was 0.5% per hour (23.7% at 48 hours). For those whose intended treatment was surgical, 48-hour mortality was 4.4%. In the surgical group, 51 patients (1%) died before the operation.

Conclusions:
and relevance
In this study, the overall mortality rate for TAAAD was 5.8% at 48 hours. For patients in the medical group, TAAAD had a mortality rate of 0.5% per hour (23.7% at 48 hours). However, among those in the surgical group, 48-hour mortality decreased to 4.4%.



JAMA Cardiol: 24 Aug 2022; epub ahead of print
Harris KM, Nienaber CA, Peterson MD, Woznicki EM, ... Isselbacher EM, Eagle KA
JAMA Cardiol: 24 Aug 2022; epub ahead of print | PMID: 36001309
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Impact:
Abstract

Self-expanding Transcatheter vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients: 5-Year Outcomes of the SURTAVI Randomized Clinical Trial.

Van Mieghem NM, Deeb GM, Søndergaard L, Grube E, ... Reardon MJ, SURTAVI Trial Investigators
Importance
In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited.
Objective
To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial.
Design, setting, and participants
SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021.
Intervention
Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis.
Main outcomes and measures
The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years.
Results
A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention.

Conclusions:
and relevance
Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.



JAMA Cardiol: 24 Aug 2022; epub ahead of print
Van Mieghem NM, Deeb GM, Søndergaard L, Grube E, ... Reardon MJ, SURTAVI Trial Investigators
JAMA Cardiol: 24 Aug 2022; epub ahead of print | PMID: 36001335
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Impact:
Abstract

Advances in Imaging and Targeted Therapies for Recurrent Pericarditis: A Review.

Kumar S, Khubber S, Reyaldeen R, Agrawal A, ... Kwon DH, Klein AL
Importance
Pericarditis is the most common form of pericardial disease. Recurrence of pericarditis affects 15% to 30% of patients after the initial episode of pericarditis. Up to 50% of patients with the first recurrence have additional recurrences. These patients often progress to have colchicine-resistant and corticosteroid-dependent disease. Rapidly evolving cardiac magnetic resonance imaging techniques and novel targeted therapies have paved the way for imaging-guided therapy for recurrent pericarditis. However, the optimal application of these recent advances remains unclear.
Observations
A search was conducted using the PubMed and Cochrane databases for English-language studies, management guidelines, meta-analyses, and review articles published until April 2022 on recurrent pericarditis. Following the 2015 European Society of Cardiology guidelines for the diagnosis and management of pericardial diseases, new clinical trials and registry data have emerged that demonstrate the efficacy of interleukin-1 blockers in recurrent pericarditis. In addition, new observational data have come to light supporting the use of cardiac magnetic resonance imaging in the diagnosis, risk stratification, and management of such patients.

Conclusions:
and relevance
Advances in imaging and targeted therapies have led to a paradigm shift in the management of recurrent pericarditis. This narrative review summarizes the established and emerging data on the diagnosis and treatment of recurrent pericarditis with special emphasis on the role of cardiac magnetic resonance imaging and interleukin-1 blockers in the current era of tailored therapy for recurrent pericarditis.



JAMA Cardiol: 17 Aug 2022; epub ahead of print
Kumar S, Khubber S, Reyaldeen R, Agrawal A, ... Kwon DH, Klein AL
JAMA Cardiol: 17 Aug 2022; epub ahead of print | PMID: 35976625
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Impact:
Abstract

Association of Transcatheter Aortic Valve Replacement Reimbursement, New Technology Add-on Payment, and Procedure Volumes With Embolic Protection Device Use.

Lowenstern A, Hung A, Manandhar P, Wegermann ZK, ... Cohen DJ, Vemulapalli S
Importance
In the setting of uncertain efficacy and additional, unreimbursed cost, use of an embolic protection device (EPD) during transcatheter aortic valve replacement (TAVR) has had variable uptake. The Centers for Medicare & Medicaid Services (CMS) instituted a new technology add-on payment to cover EPD use in October 2018.
Objective
To evaluate the association between CMS TAVR reimbursement rates and EPD use.
Design, setting, and participants
This cohort study used the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry to identify patients who underwent TAVR between January 2018 and September 2019. Analysis took place between July 2020 and February 2022.
Main outcomes and measures
The association between EPD use and CMS reimbursement was assessed using multivariable logistic regression models adjusted for patient characteristics (model 1) and patient/hospital (annualized TAVR volume and teaching status) characteristics (model 2).
Results
Among 511 institutions, CMS reimbursement for TAVR ranged from $28 062 to $111 280 with a median (IQR) of $45 884 ($40 331-$53 627). Among 84 353 patients (median [IQR] age, 81.0 [75.0-86.0] years; 46 247 male individuals [54.8%]; 3958 [4.7%] of Hispanic or Latino ethnicity; 78 170 White individuals [92.7%]) treated at the sites, 6012 (7.1%) underwent TAVR with EPD. Patient characteristics associated with EPD use included prior stroke (adjusted odds ratio [aOR], 1.13 [95% CI, 1.00-1.27]; P = .048), female sex (aOR, 0.85 [95% CI, 0.78-0.93]; P < .001), hemodialysis (aOR, 0.52 [95% CI, 0.40-0.68]; P < .001), and shock (aOR, 0.62 [95% CI, 0.41-0.94]; P = .03). Higher CMS reimbursement up to $50 000 per TAVR was associated with greater likelihood of EPD use in model 1 (per $1000; aOR, 1.08 [95% CI, 1.01-1.16]; P = .02). However, this association was no longer apparent after adjusting for site characteristics (model 2; aOR, 1.03 [95% CI, 0.96-1.11]; P = .38). Higher TAVR volume was associated with increased EPD use (per 25 TAVRs; aOR, 1.15 [95% CI, 1.09-1.21]; P < .001). There was no significant change in the odds of EPD uptake before vs after institution of the CMS new technology add-on payment across tertiles of CMS TAVR reimbursement (Wald χ2 = 3.59; P = .17).

Conclusions:
and relevance
EPD use during TAVR remains infrequent and is associated with multiple patient and site characteristics. While CMS reimbursement varies significantly across institutions, TAVR case volume, rather than CMS TAVR reimbursement or the CMS new technology add-on payment, appears to be the predominant factor associated with EPD use. Ongoing work is needed to understand the economic drivers that contribute to the association between procedural volume and EPD use.



JAMA Cardiol: 17 Aug 2022; epub ahead of print
Lowenstern A, Hung A, Manandhar P, Wegermann ZK, ... Cohen DJ, Vemulapalli S
JAMA Cardiol: 17 Aug 2022; epub ahead of print | PMID: 35976635
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Impact:
Abstract

Alerting Clinicians to 1-Year Mortality Risk in Patients Hospitalized With Heart Failure: The REVEAL-HF Randomized Clinical Trial.

Ahmad T, Desai NR, Yamamoto Y, Biswas A, ... Velazquez EJ, Wilson FP
Importance
Heart failure is a major cause of morbidity and mortality worldwide. The use of risk scores has the potential to improve targeted use of interventions by clinicians that improve patient outcomes, but this hypothesis has not been tested in a randomized trial.
Objective
To evaluate whether prognostic information in heart failure translates into improved decisions about initiation and intensity of treatment, more appropriate end-of-life care, and a subsequent reduction in rates of hospitalization or death.
Design, setting, and participants
This was a pragmatic, multicenter, electronic health record-based, randomized clinical trial across the Yale New Haven Health System, comprising small community hospitals and large tertiary care centers. Patients hospitalized for heart failure who had N-terminal pro-brain natriuretic peptide (NT-proBNP) levels of greater than 500 pg/mL and received intravenous diuretics within 24 hours of admission were automatically randomly assigned to the alert (intervention) or usual-care groups.
Interventions
The alert group had their risk of 1-year mortality calculated using an algorithm that was derived and validated using similar historic patients in the electronic health record. This estimate, including a categorical risk assessment, was presented to clinicians while they were interacting with a patient\'s electronic health record.
Main outcomes and measures
The primary outcome was a composite of 30-day hospital readmissions and all-cause mortality at 1 year.
Results
Between November 27, 2019, through March 7, 2021, 3124 patients were randomly assigned to the alert (1590 [50.9%]) or usual-care (1534 [49.1%]) group. The alert group had a median (IQR) age of 76.5 (65-86) years, and 796 were female patients (50.1%). Patients from the following race and ethnicity groups were included: 13 Asian (0.8%), 324 Black (20.4%), 136 Hispanic (8.6%), 1448 non-Hispanic (91.1%), 1126 White (70.8%), 6 other ethnicity (0.4%), and 127 other race (8.0%). The usual-care group had a median (IQR) age of 77 (65-86) years, and 788 were female patients (51.4%). Patients from the following race and ethnicity groups were included: 11 Asian (1.4%), 298 Black (19.4%), 162 Hispanic (10.6%), 1359 non-Hispanic (88.6%), 1077 White (70.2%), 13 other ethnicity (0.9%), and 137 other race (8.9%). Median (IQR) NT-proBNP levels were 3826 (1692-8241) pg/mL in the alert group and 3867 (1663-8917) pg/mL in the usual-care group. A total of 284 patients (17.9%) and 270 patients (17.6%) were admitted to the intensive care unit in the alert and usual-care groups, respectively. A total of 367 patients (23.1%) and 359 patients (23.4%) had a left ventricular ejection fraction of 40% or less in the alert and usual-care groups, respectively. The model achieved an area under the curve of 0.74 in the trial population. The primary outcome occurred in 619 patients (38.9%) in the alert group and 603 patients (39.3%) in the usual-care group (P = .89). There were no significant differences between study groups in the prescription of heart failure medications at discharge, the placement of an implantable cardioverter-defibrillator, or referral to palliative care.

Conclusions:
and relevance
Provision of 1-year mortality estimates during heart failure hospitalization did not affect hospitalization or mortality, nor did it affect clinical decision-making.
Trial registration
ClinicalTrials.gov Identifier NCT03845660.



JAMA Cardiol: 10 Aug 2022; epub ahead of print
Ahmad T, Desai NR, Yamamoto Y, Biswas A, ... Velazquez EJ, Wilson FP
JAMA Cardiol: 10 Aug 2022; epub ahead of print | PMID: 35947362
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Impact:
Abstract

Assessment of the Diagnostic Yield of Combined Cardiomyopathy and Arrhythmia Genetic Testing.

Dellefave-Castillo LM, Cirino AL, Callis TE, Esplin ED, ... Nussbaum RL, McNally EM
Importance
Genetic testing can guide management of both cardiomyopathies and arrhythmias, but cost, yield, and uncertain results can be barriers to its use. It is unknown whether combined disease testing can improve diagnostic yield and clinical utility for patients with a suspected genetic cardiomyopathy or arrhythmia.
Objective
To evaluate the diagnostic yield and clinical management implications of combined cardiomyopathy and arrhythmia genetic testing through a no-charge, sponsored program for patients with a suspected genetic cardiomyopathy or arrhythmia.
Design, setting, and participants
This cohort study involved a retrospective review of DNA sequencing results for cardiomyopathy- and arrhythmia-associated genes. The study included 4782 patients with a suspected genetic cardiomyopathy or arrhythmia who were referred for genetic testing by 1203 clinicians; all patients participated in a no-charge, sponsored genetic testing program for cases of suspected genetic cardiomyopathy and arrhythmia at a single testing site from July 12, 2019, through July 9, 2020.
Main outcomes and measures
Positive gene findings from combined cardiomyopathy and arrhythmia testing were compared with findings from smaller subtype-specific gene panels and clinician-provided diagnoses.
Results
Among 4782 patients (mean [SD] age, 40.5 [21.3] years; 2551 male [53.3%]) who received genetic testing, 39 patients (0.8%) were Ashkenazi Jewish, 113 (2.4%) were Asian, 571 (11.9%) were Black or African American, 375 (7.8%) were Hispanic, 2866 (59.9%) were White, 240 (5.0%) were of multiple races and/or ethnicities, 138 (2.9%) were of other races and/or ethnicities, and 440 (9.2%) were of unknown race and/or ethnicity. A positive result (molecular diagnosis) was confirmed in 954 of 4782 patients (19.9%). Of those, 630 patients with positive results (66.0%) had the potential to inform clinical management associated with adverse clinical outcomes, increased arrhythmia risk, or targeted therapies. Combined cardiomyopathy and arrhythmia gene panel testing identified clinically relevant variants for 1 in 5 patients suspected of having a genetic cardiomyopathy or arrhythmia. If only patients with a high suspicion of genetic cardiomyopathy or arrhythmia had been tested, at least 137 positive results (14.4%) would have been missed. If testing had been restricted to panels associated with the clinician-provided diagnostic indications, 75 of 689 positive results (10.9%) would have been missed; 27 of 75 findings (36.0%) gained through combined testing involved a cardiomyopathy indication with an arrhythmia genetic finding or vice versa. Cascade testing of family members yielded 402 of 958 positive results (42.0%). Overall, 2446 of 4782 patients (51.2%) had only variants of uncertain significance. Patients referred for arrhythmogenic cardiomyopathy had the lowest rate of variants of uncertain significance (81 of 176 patients [46.0%]), and patients referred for catecholaminergic polymorphic ventricular tachycardia had the highest rate (48 of 76 patients [63.2%]).

Conclusions:
and relevance
In this study, comprehensive genetic testing for cardiomyopathies and arrhythmias revealed diagnoses that would have been missed by disease-specific testing. In addition, comprehensive testing provided diagnostic and prognostic information that could have potentially changed management and monitoring strategies for patients and their family members. These results suggest that this improved diagnostic yield may outweigh the burden of uncertain results.



JAMA Cardiol: 10 Aug 2022; epub ahead of print
Dellefave-Castillo LM, Cirino AL, Callis TE, Esplin ED, ... Nussbaum RL, McNally EM
JAMA Cardiol: 10 Aug 2022; epub ahead of print | PMID: 35947370
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Impact:
Abstract

Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.

Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, ... Hovingh GK, Schmidt AF
Importance
Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.
Objective
To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.
Design, setting, and participants
Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.
Exposures
Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.
Main outcomes and measures
Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.
Results
Data for 425 354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229 399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P = .34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P = .83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).

Conclusions:
and relevance
Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.



JAMA Cardiol: 03 Aug 2022; epub ahead of print
Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, ... Hovingh GK, Schmidt AF
JAMA Cardiol: 03 Aug 2022; epub ahead of print | PMID: 35921096
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Impact:
Abstract

Association Between Early Left Ventricular Ejection Fraction Improvement After Transcatheter Aortic Valve Replacement and 5-Year Clinical Outcomes.

Kolte D, Bhardwaj B, Lu M, Alu MC, ... Mack MJ, Elmariah S
Importance
In patients with severe aortic stenosis and left ventricular ejection fraction (LVEF) less than 50%, early LVEF improvement after transcatheter aortic valve replacement (TAVR) is associated with improved 1-year mortality; however, its association with long-term clinical outcomes is not known.
Objective
To examine the association between early LVEF improvement after TAVR and 5-year outcomes.
Design, setting, and participants
This cohort study analyzed patients enrolled in the Placement of Aortic Transcatheter Valves (PARTNER) 1, 2, and S3 trials and registries between July 2007 and April 2015. High- and intermediate-risk patients with baseline LVEF less than 50% who underwent transfemoral TAVR were included in the current study. Data were analyzed from August 2020 to May 2021.
Exposures
Early LVEF improvement, defined as increase of 10 percentage points or more at 30 days and also as a continuous variable (ΔLVEF between baseline and 30 days).
Main outcomes and measures
All-cause death at 5 years.
Results
Among 659 included patients with LVEF less than 50%, 468 (71.0%) were male, and the mean (SD) age was 82.4 (7.7) years. LVEF improvement within 30 days following transfemoral TAVR occurred in 216 patients (32.8%) (mean [SD] ΔLVEF, 16.4 [5.7%]). Prior myocardial infarction, diabetes, cancer, higher baseline LVEF, larger left ventricular end-diastolic diameter, and larger aortic valve area were independently associated with lower likelihood of LVEF improvement. Patients with vs without early LVEF improvement after TAVR had lower 5-year all-cause death (102 [50.0%; 95% CI, 43.3-57.1] vs 246 [58.4%; 95% CI, 53.6-63.2]; P = .04) and cardiac death (52 [29.5%; 95% CI, 23.2-37.1] vs 135 [38.1%; 95% CI, 33.1-43.6]; P = .05). In multivariable analyses, early improvement in LVEF (modeled as a continuous variable) was associated with lower 5-year all-cause death (adjusted hazard ratio per 5% increase in LVEF, 0.94 [95% CI, 0.88-1.00]; P = .04) and cardiac death (adjusted hazard ratio per 5% increase in LVEF, 0.90 [95% CI, 0.82-0.98]; P = .02) after TAVR. Restricted cubic spline analysis demonstrated a visual inflection point at ΔLVEF of 10% beyond which there was a steep decline in all-cause mortality with increasing degree of LVEF improvement. There were no statistically significant differences in rehospitalization, New York Heart Association functional class, or Kansas City Cardiomyopathy Questionnaire Overall Summary score at 5 years in patients with vs without early LVEF improvement. In subgroup analysis, the association between early LVEF improvement and 5-year all-cause death was consistent regardless of the presence or absence of coronary artery disease or prior myocardial infarction.

Conclusions:
and relevance
In patients with severe aortic stenosis and LVEF less than 50%, 1 in 3 experience LVEF improvement within 1 month after TAVR. Early LVEF improvement is associated with lower 5-year all-cause and cardiac death.



JAMA Cardiol: 27 Jul 2022; epub ahead of print
Kolte D, Bhardwaj B, Lu M, Alu MC, ... Mack MJ, Elmariah S
JAMA Cardiol: 27 Jul 2022; epub ahead of print | PMID: 35895046
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Impact:
Abstract

Demographic and Regional Trends of Heart Failure-Related Mortality in Young Adults in the US, 1999-2019.

Jain V, Minhas AMK, Morris AA, Greene SJ, ... Butler J, Khan MS
Importance
There are limited data on mortality trends in young adults with heart failure (HF).
Objective
To study the trends in HF-related mortality among young adults.
Design, setting, and participants
This retrospective cohort analysis used mortality data of young adults aged 15 to 44 years with HF listed as a contributing or underlying cause of death in the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 1999 to December 2019. Analysis took place in October 2021.
Exposures
Age 15 to 44 years with HF listed as a contributing or underlying cause of death.
Main outcomes and measures
HF-related age-adjusted mortality rates (AAMR) per 100 000 US population stratified by sex, race and ethnicity, and geographic areas.
Results
Between 1999 and 2019, a total of 61 729 HF-related deaths occurred in young adults. Of these, 38 629 (62.0%) were men and 23 460 (38.0%) were women, and 22 156 (35.9%) were Black, 6648 (10.8%) were Hispanic, and 30 145 (48.8%) were White. The overall AAMR per 100 000 persons for HF in young adults increased from 2.36 in 1999 to 3.16 in 2019. HF mortality increased in young men and women, with men having higher AAMRs throughout the study period. AAMR increased for all race and ethnicity groups, with Black adults having the highest AAMRs (6.41 in 1999 and 8.58 in 2019). AAMR for Hispanic adults and White adults increased from 1.62 to 2.04 and 1.83 to 2.45 over the same time period, respectively. Across most demographic and regional subgroups, HF-related mortality stayed stable or decreased between 1999 and 2012, followed by an increase between 2012 and 2019. There were significant regional differences in the burden of HF-related mortality, with states in the upper 90th percentile of HF-related mortality (Oklahoma, South Carolina, Louisiana, Arkansas, Alabama, and Mississippi) having a significantly higher mortality burden compared with those in the bottom tenth percentile.

Conclusions:
and relevance
Following an initial period of stability, HF-related mortality in young adults increased from 2012 to 2019 in the United States. Black adults have a 3-fold higher AAMR compared with White adults, with significant geographic variation. Targeted health policy measures are needed to address the rising burden of HF in young adults, with a focus on prevention, early diagnosis, and reduction in disparities.



JAMA Cardiol: 27 Jul 2022; epub ahead of print
Jain V, Minhas AMK, Morris AA, Greene SJ, ... Butler J, Khan MS
JAMA Cardiol: 27 Jul 2022; epub ahead of print | PMID: 35895048
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Impact:
Abstract

Efficacy and Safety of Dapagliflozin According to Background Use of Cardiovascular Medications in Patients With Type 2 Diabetes: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Oyama K, Raz I, Cahn A, Goodrich EL, ... Sabatine MS, Wiviott SD
Importance
Dapagliflozin was shown to reduce the cardiovascular (CV) and kidney outcomes in patients with type 2 diabetes. However, data are limited on the relationship of the effect and safety with the concurrent use of CV medications in patients with type 2 diabetes.
Objective
To assess whether the cardiorenal efficacy and safety of dapagliflozin were consistent with and without background use of CV medications commonly used for heart failure (HF) and kidney disease in patients with type 2 diabetes.
Design, setting, and participants
This study is a prespecified secondary analysis of DECLARE-TIMI 58, which was a randomized trial of dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and either atherosclerotic disease or multiple risk factors for CV disease. Patients were stratified by baseline use of the following CV medications: angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARBs), β-blockers, diuretics, and mineralocorticoid receptor antagonists (MRAs). The study was conducted from May 2013 to September 2018, and data were evaluated for this analysis from February 2021 to May 2022.
Interventions
Dapagliflozin or placebo.
Main outcomes and measures
The outcomes of interest were the composite of CV death or hospitalization for HF (HHF), HHF alone, and a kidney-specific composite outcome (persistent ≥40% decrease in estimated glomerular filtration rate [eGFR], end-stage kidney disease, or kidney-related death).
Results
Among 17 160 patients, 13 950 (81%) used ACEI/ARBs, 9030 (53%) used β-blockers, 6205 (36%) used diuretics, and 762 (4%) used MRAs at baseline. Changes in blood pressure and eGFR at 48 months with dapagliflozin compared with placebo did not differ regardless of concurrent therapy (placebo-corrected change, -1.6 mm Hg [95% CI, -4.2 to 1.0] to -2.6 mm Hg [95% CI, -3.3 to -2.9]; P > .05 for each interaction). Dapagliflozin consistently reduced the risk of CV death/HHF, HHF alone, and the kidney-specific composite outcome regardless of background use of selected medications (hazard ratio [HR] range: HR, 0.50; 95% CI, 0.39-0.63; to HR, 0.82; 95% CI, 0.72-0.95; P > .05 for each interaction). In patients receiving ACEI/ARBs + β-blockers + diuretics (n = 4243), dapagliflozin reduced the risk of CV death/HHF and of the kidney-specific outcome by 24% (HR, 0.76; 95% CI, 0.62-0.93) and 38% (HR, 0.62; 95% CI, 0.44-0.87), respectively. There were no significant treatment interactions with the concomitant CV medications for adverse events of volume depletion, acute kidney injury, or hyperkalemia (range: HR, 0.12; 95% CI, 0.02-0.99; to HR, 1.04; 95% CI, 0.83-1.32; P > .05 for each interaction).

Conclusions:
and relevance
Dapagliflozin consistently reduced the risk of CV and kidney outcomes irrespective of background use of various CV medications without any treatment interaction for key safety events. These data show the clinical benefit and safety of dapagliflozin in a broad range of patients with type 2 diabetes regardless of background therapy.
Trial registration
ClinicalTrials.gov Identifier: NCT01730534.



JAMA Cardiol: 20 Jul 2022; epub ahead of print
Oyama K, Raz I, Cahn A, Goodrich EL, ... Sabatine MS, Wiviott SD
JAMA Cardiol: 20 Jul 2022; epub ahead of print | PMID: 35857296
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Impact:
Abstract

Association of Left Ventricular Remodeling Assessment by Cardiac Magnetic Resonance With Outcomes in Patients With Chronic Aortic Regurgitation.

Hashimoto G, Enriquez-Sarano M, Stanberry LI, Oh F, ... Lesser J, Cavalcante JL
Importance
Chronic aortic regurgitation (AR) causes left ventricular (LV) volume overload, which results in progressive LV remodeling negatively affecting outcomes. Whether cardiac magnetic resonance (CMR) volumetric quantification can provide incremental risk stratification over standard clinical and echocardiographic evaluation in patients with chronic moderate or severe AR is unknown.
Objective
To compare LV remodeling measurements by CMR and echocardiography between patients with and without heart failure symptoms and to verify the association of remodeling measurements of patients with chronic moderate or severe AR but no or minimal symptoms with clinical outcomes receiving medical management.
Design, setting, and participants
This multicenter retrospective cohort study included consecutive patients with at least moderate chronic native AR evaluated by 2-dimensional transthoracic echocardiography and CMR examination within 90 days from each other between January 2012 and February 2020 at Allina Health System. Data were analyzed from June 2021 to January 2022.
Exposures
Clinical evaluation and risk stratification by CMR.
Main outcomes and measures
The end point was a composite of death, heart failure hospitalization, or progression of New York Heart Association functional class while receiving medical management, censoring patients at the time of aortic valve replacement (when performed) or at the end of follow-up.
Results
Of the 178 included patients, 119 (66.9%) were male, 158 (88.8%) presented with no or minimal symptoms (New York Heart Association class I or II), and the median (IQR) age was 58 (44-69) years. Compared with patients with no or minimal symptoms, symptomatic patients had greater LV end-systolic volume index (LVESVi) by CMR (median [IQR], 66 [46-85] mL/m2 vs 42 [30-58] mL/m2; P < .001), while there were no significant differences by echocardiography (LVESVi: median [IQR], 38 [30-58] mL/m2 vs 27 [20-42] mL/m2; P = .07; LV end-systolic diameter index: median [IQR], 21 [17-25] mm/m2 vs 18 [15-22] mm/m2; P = .17). During the median (IQR) follow-up of 3.3 (1.6-5.8) years, 50 patients with no or minimal symptoms receiving medical management developed the composite end point, which, in multivariate analysis adjusted for age and EuroSCORE II, was independently associated with LVESVi of 45 mL/m2 or greater and aortic regurgitant fraction of 32% or greater, the latter adding incremental prognostic value to CMR volumetric assessment.

Conclusions:
and relevance
In patients with chronic moderate or severe AR, patients presenting with heart failure symptoms have greater LVESVi by CMR than those with no or minimal symptoms. In patients with no or minimal symptoms, CMR quantification of LVESVi and AR severity may identify those at risk of death or incident heart failure and therefore should be considered in the clinical evaluation and decision-making of these patients.



JAMA Cardiol: 20 Jul 2022; epub ahead of print
Hashimoto G, Enriquez-Sarano M, Stanberry LI, Oh F, ... Lesser J, Cavalcante JL
JAMA Cardiol: 20 Jul 2022; epub ahead of print | PMID: 35857306
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Impact:
Abstract

Clinical Presentation and Short- and Long-term Outcomes in Patients With Isolated Distal Deep Vein Thrombosis vs Proximal Deep Vein Thrombosis in the RIETE Registry.

Bikdeli B, Caraballo C, Trujillo-Santos J, Galanaud JP, ... Monreal M, RIETE Investigators
Importance
Insufficient data exist about the clinical presentation, short-term, and long-term outcomes of patients with isolated distal deep vein thrombosis (IDDVT), that is, thrombosis in infrapopliteal veins without proximal extension or pulmonary embolism (PE).
Objective
To determine the clinical characteristics, short-term, and 1-year outcomes in patients with IDDVT and to compare the outcomes in unadjusted and multivariable adjusted analyses with patients who had proximal DVT.
Design, setting, and participants
This was a multicenter, international cohort study in participating sites of the Registro Informatizado Enfermedad Tromboembólica (RIETE) registry conducted from March 1, 2001, through February 28, 2021. Patients included in this study had IDDVT. Patients with proximal DVT were identified for comparison. Patients were excluded if they had a history of asymptomatic DVT, upper-extremity DVT, coexisting PE, or COVID-19 infection.
Main outcomes and measures
Primary outcomes were 90-day and 1-year mortality, 1-year major bleeding, and 1-year venous thromboembolism (VTE) deterioration, which was defined as subsequent development of proximal DVT or PE.
Results
A total of 33 897 patients were identified with isolated DVT (without concomitant PE); 5938 (17.5%) had IDDVT (mean [SD] age, 61 [17] years; 2975 male patients [50.1%]), and 27 959 (82.5%) had proximal DVT (mean [SD] age, 65 [18] years; 14 315 male patients [51.2%]). Compared with individuals with proximal DVT, those with IDDVT had a lower comorbidity burden but were more likely to have had recent surgery or to have received hormonal therapy. Patients with IDDVT had lower risk of 90-day mortality compared with those with proximal DVT (odds ratio [OR], 0.47; 95% CI, 0.40-0.55). Findings were similar in 1-year unadjusted analyses (hazard ratio [HR], 0.52; 95% CI, 0.46-0.59) and adjusted analyses (HR, 0.72; 95% CI, 0.64-0.82). Patients with IDDVT had a lower 1-year hazard of VTE deterioration (HR, 0.83; 95% CI, 0.69-0.99). In 1-year adjusted analyses of patients without an adverse event within the first 3 months, IDDVT was associated with lower risk of VTE deterioration (adjusted HR, 0.48; 95% CI, 0.24-0.97). By 1-year follow-up, symptoms or signs of postthrombotic syndrome were less common in patients with IDDVT (47.6% vs 60.5%).

Conclusions:
and relevance
Results of this cohort study suggest that patients with IDDVT had a less ominous prognosis compared with patients with proximal DVT. Such differences were likely multifactorial, including the differences in demographics, risk factors, comorbidities, particularly for all-cause mortality, and a potential association of thrombus location with VTE deterioration and postthrombotic syndrome. Randomized clinical trials are needed to assess the optimal long-term management of IDDVT.



JAMA Cardiol: 13 Jul 2022; epub ahead of print
Bikdeli B, Caraballo C, Trujillo-Santos J, Galanaud JP, ... Monreal M, RIETE Investigators
JAMA Cardiol: 13 Jul 2022; epub ahead of print | PMID: 35830171
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Impact:
Abstract

Diagnosis of Heart Failure With Preserved Ejection Fraction Among Patients With Unexplained Dyspnea.

Reddy YNV, Kaye DM, Handoko ML, van de Bovenkamp AA, ... Redfield MM, Borlaug BA
Importance
Diagnosis of heart failure with preserved ejection fraction (HFpEF) among dyspneic patients without overt congestion is challenging. Multiple diagnostic approaches have been proposed but are not well validated against the independent gold standard for HFpEF diagnosis of an elevated pulmonary capillary wedge pressure (PCWP) during exercise.
Objective
To evaluate H2FPEF and HFA-PEFF scores and a PCWP/cardiac output (CO) slope of more than 2 mm Hg/L/min to diagnose HFpEF.
Design, setting, and participants
This retrospective case-control study included patients with unexplained dyspnea from 6 centers in the US, the Netherlands, Denmark, and Australia from March 2016 to October 2020. Diagnosis of HFpEF (cases) was definitively ascertained by the presence of elevated PCWP during exertion; control individuals were those with normal rest and exercise hemodynamics.
Main outcomes and measures
Logistic regression was used to evaluate the accuracy of HFA-PEFF and H2FPEF scores to discriminate patients with HFpEF from controls.
Results
Among 736 patients, 563 (76%) were diagnosed with HFpEF (mean [SD] age, 69 [11] years; 334 [59%] female) and 173 (24%) represented controls (mean [SD] age, 60 [15] years; 109 [63%] female). H2FPEF and HFA-PEFF scores discriminated patients with HFpEF from controls, but the H2FPEF score had greater area under the curve (0.845; 95% CI, 0.810-0.875) compared with the HFA-PEFF score (0.710; 95% CI, 0.659-0.756) (difference, -0.134; 95% CI, -0.177 to -0.094; P < .001). Specificity was robust for both scores, but sensitivity was poorer for HFA-PEFF, with a false-negative rate of 55% for low-probability scores compared with 25% using the H2FPEF score. Use of the PCWP/CO slope to redefine HFpEF rather than exercise PCWP reclassified 20% (117 of 583) of patients, but patients reclassified from HFpEF to control by this metric had clinical, echocardiographic, and hemodynamic features typical of HFpEF, including elevated resting PCWP in 66% (46 of 70) of reclassified patients.

Conclusions:
and relevance
In this case-control study, despite requiring fewer data, the H2FPEF score had superior diagnostic performance compared with the HFA-PEFF score and PCWP/CO slope in the evaluation of unexplained dyspnea and HFpEF in the outpatient setting.



JAMA Cardiol: 13 Jul 2022; epub ahead of print
Reddy YNV, Kaye DM, Handoko ML, van de Bovenkamp AA, ... Redfield MM, Borlaug BA
JAMA Cardiol: 13 Jul 2022; epub ahead of print | PMID: 35830183
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Impact:
Abstract

Statin Eligibility for Primary Prevention of Cardiovascular Disease According to 2021 European Prevention Guidelines Compared With Other International Guidelines.

Mortensen MB, Tybjærg-Hansen A, Nordestgaard BG
Importance
For primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2021 European Society of Cardiology (ESC) guidelines on statin use (hereafter European-ESC) recommend a new risk model (Systematic Coronary Risk Evaluation 2 [European-SCORE2]) as well as new age-specific treatment thresholds (≥7.5% 10-year ASCVD risk if aged 40-49 years and ≥10% if aged 50-69 years).
Objective
To compare the clinical performance of the 2021 European-ESC, American College of Cardiology/American Heart Association (hereafter US-ACC/AHA), UK National Institute for Health and Care Excellence (UK-NICE), and 2019 ESC/European Atherosclerosis Society (EAS) guidelines in apparently healthy individuals.
Design, setting, and participants
This population-based contemporary cohort study included 66 909 individuals from the Copenhagen General Population Study. Participants were aged 40 to 69 years and were free of ASCVD, diabetes, chronic kidney disease, and statin use at baseline in 2003 to 2015. Mean follow-up time was 9.2 years. Data were analyzed from November 2021 to April 2022.
Exposures
Statin treatment according to guideline criteria.
Main outcomes and measures
Calibration of risk calculators, statin eligibility, sensitivity, and specificity for ASCVD events according to guideline criteria.
Results
During follow-up, a range of 2962 to 4277 nonfatal and fatal ASCVD events was observed, as defined by the 2021 European-SCORE2, US pooled cohort equations (PCE), and UK-QRISK3 models, and 180 fatal ASCVD events were noted as defined by the 2019 European-SCORE1 model. European-SCORE2 was slightly better calibrated with a predicted/observed ASCVD event ratio of 0.8 vs 1.3 for US-PCE, 1.3 for UK-QRISK3, and 5.8 for European-SCORE1. For primary prevention class I recommendations in individuals aged 40 to 69 years, 2862 of 66 909 (4%) qualified for statins according to the 2021 European-ESC guidelines compared with 23 029 (34%) with US-ACC/AHA, 17 659 (26%) with UK-NICE, and 13 496 (20%) with 2019 European-ESC/EAS guidelines, with associated sensitivities for detecting future European-SCORE2-defined ASCVD events of 12%, 60%, 51%, and 36%, respectively. The sensitivity of the European-ESC guidelines was improved considerably by lowering the treatment thresholds, resulting in smaller losses in specificity. To obtain similar clinical performance with the 2021 European-ESC guidelines as in the other guidelines, the threshold with European-SCORE2 should be reduced to 5% overall to match US-ACC/AHA, to 6% to match UK-NICE, and to 7% to match 2019 European-ESC/EAS guidelines.

Conclusions:
and relevance
Despite an improved European-SCORE2 prediction model, the new treatment thresholds in the 2021 European-ESC guidelines dramatically reduce eligibility for primary prevention with statins in low-risk European countries. Using lower treatment thresholds can improve overall guideline performance.



JAMA Cardiol: 06 Jul 2022; epub ahead of print
Mortensen MB, Tybjærg-Hansen A, Nordestgaard BG
JAMA Cardiol: 06 Jul 2022; epub ahead of print | PMID: 35793078
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Impact:
Abstract

Machine Learning-Based Models Incorporating Social Determinants of Health vs Traditional Models for Predicting In-Hospital Mortality in Patients With Heart Failure.

Segar MW, Hall JL, Jhund PS, Powell-Wiley TM, ... Stevens LM, Pandey A
Importance
Traditional models for predicting in-hospital mortality for patients with heart failure (HF) have used logistic regression and do not account for social determinants of health (SDOH).
Objective
To develop and validate novel machine learning (ML) models for HF mortality that incorporate SDOH.
Design, setting, and participants
This retrospective study used the data from the Get With The Guidelines-Heart Failure (GWTG-HF) registry to identify HF hospitalizations between January 1, 2010, and December 31, 2020. The study included patients with acute decompensated HF who were hospitalized at the GWTG-HF participating centers during the study period. Data analysis was performed January 6, 2021, to April 26, 2022. External validation was performed in the hospitalization cohort from the Atherosclerosis Risk in Communities (ARIC) study between 2005 and 2014.
Main outcomes and measures
Random forest-based ML approaches were used to develop race-specific and race-agnostic models for predicting in-hospital mortality. Performance was assessed using C index (discrimination), regression slopes for observed vs predicted mortality rates (calibration), and decision curves for prognostic utility.
Results
The training data set included 123 634 hospitalized patients with HF who were enrolled in the GWTG-HF registry (mean [SD] age, 71 [13] years; 58 356 [47.2%] female individuals; 65 278 [52.8%] male individuals. Patients were analyzed in 2 categories: Black (23 453 [19.0%]) and non-Black (2121 [2.1%] Asian; 91 154 [91.0%] White, and 6906 [6.9%] other race and ethnicity). The ML models demonstrated excellent performance in the internal testing subset (n = 82 420) (C statistic, 0.81 for Black patients and 0.82 for non-Black patients) and in the real-world-like cohort with less than 50% missingness on covariates (n = 553 506; C statistic, 0.74 for Black patients and 0.75 for non-Black patients). In the external validation cohort (ARIC registry; n = 1205 Black patients and 2264 non-Black patients), ML models demonstrated high discrimination and adequate calibration (C statistic, 0.79 and 0.80, respectively). Furthermore, the performance of the ML models was superior to the traditional GWTG-HF risk score model (C index, 0.69 for both race groups) and other rederived logistic regression models using race as a covariate. The performance of the ML models was identical using the race-specific and race-agnostic approaches in the GWTG-HF and external validation cohorts. In the GWTG-HF cohort, the addition of zip code-level SDOH parameters to the ML model with clinical covariates only was associated with better discrimination, prognostic utility (assessed using decision curves), and model reclassification metrics in Black patients (net reclassification improvement, 0.22 [95% CI, 0.14-0.30]; P < .001) but not in non-Black patients.

Conclusions:
and relevance
ML models for HF mortality demonstrated superior performance to the traditional and rederived logistic regressions models using race as a covariate. The addition of SDOH parameters improved the prognostic utility of prediction models in Black patients but not non-Black patients in the GWTG-HF registry.



JAMA Cardiol: 06 Jul 2022; epub ahead of print
Segar MW, Hall JL, Jhund PS, Powell-Wiley TM, ... Stevens LM, Pandey A
JAMA Cardiol: 06 Jul 2022; epub ahead of print | PMID: 35793094
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Impact:

This program is still in alpha version.