Publications

BACKGROUND: Prompt revascularization is crucial for managing for chronic limb-threatening ischemia (CLTI), but disparities in socioeconomic status (SES) and health care access affect outcomes. The COVID-19 pandemic exacerbated these inequities, yet their impact on CLTI outcomes remains underexplored. This study evaluated the association between regional SES, measured by the Distressed Communities Index (DCI), and outcomes-including mortality, major amputation, and repeat interventions-before, during, and after the COVID-19 pandemic in Medicare beneficiaries undergoing CLTI revascularization.

METHODS: From 2016 to 2023, Medicare beneficiaries undergoing CLTI endovascular revascularization were stratified by SES using the DCI (distressed, ≥80th percentile). The study periods were prepandemic (January 1, 2016, to March 31, 2020), pandemic (March 31, 2020, to December 31, 2021), and late pandemic (December 31, 2021, to December 31, 2023). Metrics were evaluated before and after revascularization. End points were analyzed using Kaplan-Meier and Cox models adjusted for demographics and clinical factors.

RESULTS: Among 333,173 beneficiaries, 66,757 (20.0%) lived in distressed communities, facing higher risks of major amputation and mortality (hazard ratio [HR] 1.04; 95% confidence interval [CI], 1.03-1.05; P < .001). These disparities persisted across the entire study period, including the prepandemic, pandemic, and postpandemic eras. Before the pandemic, risks were elevated (HR, 1.01; 95% CI, 1.00-1.03; P = .125), worsening during the pandemic (HR, 1.06; 95% CI, 1.03-1.09; P < .001) and late pandemic (HR, 1.07; 95% CI, 1.03-1.11; P < .001). The proportion of percutaneous vascular interventions in distressed communities decreased annually (-0.59%; 95% CI, -0.68% to -0.50%; P < .0001). These patients had fewer vascular visits (before, 5.62 vs 6.63; after, 6.52 vs 7.57; P < .001) but more emergency department visits (0.04 vs 0.03; P < .001) and hospital readmissions (0.13 vs 0.11; P < .001).

CONCLUSIONS: Socioeconomic disparities, measured by the DCI, affect outcomes and health care use in Medicare beneficiaries with CLTI undergoing revascularization. These gaps worsened during COVID-19 and persisted after the pandemic, highlighting the need for resources to bridge the care gap and improve CLTI management.

BACKGROUND: Based on the landmark PLATO (Platelet Inhibition and Patient Outcomes) and TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction) trials, current guidelines recommend ticagrelor and prasugrel over clopidogrel for acute coronary syndrome. However, subsequent studies have failed to replicate the reported benefits of ticagrelor, raising concerns about the validity of the PLATO trial's findings.

METHODS: Randomized trials published until January 2025 were searched on PubMed and Embase and included if they compared 2 of the 3 standard dual antiplatelet therapies: 12 months aspirin plus clopidogrel, prasugrel, or ticagrelor. We constructed a network with and without PLATO to assess its impact on the synthesized risk estimates on major adverse cardiovascular events, patient mortality, myocardial infarction, and stent thrombosis, as well as major bleeding and major or minor bleeding.

RESULTS: Twelve trials, enrolling 52 415 patients (clopidogrel: 23 557; ticagrelor: 13 344, prasugrel: 15 514) were included. The analysis with PLATO showed lower hazard ratios for ticagrelor versus clopidogrel than the analysis without PLATO in major adverse cardiovascular events, mortality, myocardial infarction, and bleeding outcomes (e.g., cardiovascular mortality; hazard ratio [HR], 0.83 [95% CI, 0.72-0.96] when PLATO was included; HR, 0.96 [95% CI, 0.73-1.25] when PLATO was excluded). Ticagrelor and prasugrel were associated with higher incidences of major bleeding and major or minor bleeding for analyses including and excluding PLATO, altohugh the point estimates for ticagrelor were lower when PLATO was included.

CONCLUSIONS: The pooled estimates with PLATO favored ticagrelor compared with estimates without PLATO in several studied outcomes, potentially suggesting the substantial impacts of PLATO's findings on the pooled risk estimates; therefore, additional evidence may be needed given the large number of patients worldwide treated with dual antiplatelet therapy.

Renal denervation has recently emerged as a novel approach to improving blood pressure control, particularly in patients with uncontrolled or resistant hypertension. Although a substantial body of evidence has accumulated regarding the procedure's efficacy and safety, considerable variation exists across studies in the primary measures used to assess treatment response. The degree of response also differs widely among individuals, highlighting the importance of identifying factors associated with enhanced or limited responses to the procedure. In this review, we summarize the currently available evidence on response parameters and predictors of response to renal denervation and offer perspectives for future research.

Renal denervation (RDN) is an interventional approach that targets the sympathetic nervous system with the goal of modulating its activity, an important contributor to the pathogenesis of many cardiovascular and metabolic diseases. Unlike pharmacologic therapies, RDN efficacy is independent of patient adherence to medications, which remains a major limiting factor in long-term blood pressure control. Initially developed to treat severe, treatment-resistant hypertension, RDN has demonstrated consistent results in recent sham-controlled trials across the spectrum of hypertension. As a result, RDN has been incorporated into European guidelines as a treatment option for select patients and endorsed by cardiovascular and hypertension societies worldwide. This review outlines the physiological rationale behind RDN, summarizes the current evidence supporting its effectiveness, provides an overview of the available technologies, and evaluates its emerging role in the treatment of chronic heart failure and other conditions characterized by high sympathetic nervous system activity. Finally, the authors explore future directions, including the concept of multiorgan denervation, which aims to achieve an enhanced degree of sympathetic modulation by targeting additional sympathetic nerves beyond the kidney.

BACKGROUND: Overactivity of the hepatic and renal sympathetic nerves is associated with chronic cardiovascular and metabolic conditions, including hypertension.

AIMS: We studied the effect of combined renal and hepatic denervation through treatment of the common hepatic artery and the renal arteries.

METHODS: Denervation was performed in the common hepatic artery and both renal arteries and their major branch vessels in normotensive swine using the same multielectrode radiofrequency (RF) ablation catheter (Symplicity Spyral). Renal and liver tissue samples were obtained for histological examination in two cohorts at 7 and 28 days post-procedure (n=5 sham, n=10 denervation for each timepoint).

RESULTS: Combined hepatic and renal denervation was successfully achieved in all animals. At 7 days, the mean lesion depth was 5.8±1.4 mm in the renal arteries and 4.7±0.7 mm in the hepatic artery. Compared with controls, the mean renal cortical norepinephrine (NE) levels were reduced by 88.2% in the 7-day model and by 84.5% in the 28-day model. Liver NE decreased by 94.6% at 7 days and by 91.1% at 28 days (p<0.0001 for all comparisons with baseline). No inadvertent injury was detected in the treated arteries or adjacent tissues.

CONCLUSIONS: Combined hepatic and renal denervation using the same multielectrode RF denervation system resulted in a substantial reduction in both renal and hepatic tissue NE levels that was sustained up to 28 days without collateral tissue injury. These mechanistic findings may have implications for the treatment of chronic diseases impacted by hepatic and renal sympathetic nervous system overactivity.

OBJECTIVE: This study compared quantitative measures of risk tolerance between two preference-elicitation methods; a discrete-choice experiment (DCE) and a probabilistic threshold technique (TT) exercise.

METHODS: A survey offered benefit-risk tradeoffs pertaining to devices used in revascularization procedures for peripheral artery disease. Survey-design features included alternating the sequence of DCE and TT exercises, testing two risk-communication approaches, and using two DCE experimental designs. The risk-tolerance metric was the maximum-acceptable risk (MAR) increase in 5-year mortality above 8% that patients would accept to choose a device offering lower repeat-procedure risks. DCE data were analyzed with mixed-logit models, and TT data were analyzed with interval regressions. Sensitivity analyses were conducted to examine the impacts of survey-design features.

RESULTS: For the full sample (N=249), MARs from the DCE and TT differed by <1 percentage-point (DCE: 13.0%; TT: 13.8%). MAR estimates were not significantly influenced by the risk-communication approach or experimental-design; however, order of DCE and TT mattered. After removing the influence of DCE and TT order, the mean MARs still differed by <1 percentage-point (MAR among those completing DCE first (n=123): 14.3%; MAR among those completing TT first (n=126): 13.7%). Although convergent validity was found at the sample level, discordance (> 2 percentage points) between individual-level DCE MAR and TT MAR were observed for approximately half (48.2%) of the sample.

CONCLUSIONS: While there was concordance between DCE and TT mean MAR estimates at the sample level, at the individual level, only half of the respondents had an absolute difference of 2 percentage-points or less.

OBJECTIVE: The optimal management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis is controversial and includes intensive medical management (i.e., best medical therapy [BMT]) with/without an additional carotid revascularization procedure (i.e., carotid endarterectomy [CEA], transfemoral carotid artery stenting [TFCAS] or TransCarotid Artery Revascularization [TCAR]). The aim of this international, expert-based, multispecialty Delphi Consensus document was to reconcile the conflicting views regarding the optimal management of AsxCS and SxCS patients.

METHODS: A three-round Delphi Consensus process was performed including 63 experts from Europe (n=37) and the United States (n=26). A total of 6 different clinical scenarios were identified involving patients with either AsxCS or SxCS. For each scenario, 5 treatment options were available: (i) BMT alone, (ii) BMT plus CEA, (iii) BMT plus TFCAS, (iv) BMT plus TCAR, or (v) BMT plus CEA/TFCAS/TCAR. Differences in treatment preferences between U.S. and European participants were assessed using Fisher's Exact Test, and odds ratios were used to quantify the magnitude and direction of association. Consensus was achieved when >70% of the Delphi Consensus participants agreed on a therapeutic approach.

RESULTS: Most participants concurred that BMT alone is not adequate for the management of a 70-year-old fit male or female patient with 80-99% AsxCS (52/63; 82.5% and 45/63; 71.5%, respectively). In contrast, most panelists would opt for BMT alone for an 80-year-old male AsxCS patient with several co-morbidities (48/63; 76.2%). The majority of participants would opt for BMT plus a carotid revascularization procedure for an 80-year-old male SxCS patient with a recent ipsilateral cerebrovascular event, an ipsilateral 70-99% SxCS and a 5-year predicted risk of ipsilateral ischemic event of 10% (54/63; 85.7%), 15% (59/63; 93.6%), or 20% (63/63; 100%). The opinion of U.S.-based participants varied from that of Europe-based respondents in some scenarios.

CONCLUSIONS: The panel agreed that BMT alone is insufficient for most patients with SxCS, and that select subgroups of AsxCS patients may also benefit from revascularization, especially when high-risk features are present. Patients should be stratified according to their predicted stroke risk, as well as their individual clinical/anatomical/imaging features and should be treated accordingly.

AIMS: Both lipoprotein(a) [Lp(a)] and peripheral artery disease (PAD) are associated with ischaemic events. We sought to assess the association between Lp(a) and major adverse cardiovascular events (MACE) and major lower extremity events (MALE) among patients with baseline PAD.

METHODS AND RESULTS: The Mass General Brigham (MGB) Lp(a) registry includes all individuals with Lp(a) measured at two tertiary care centres from 2000 to 2019. Those with PAD were grouped according to Lp(a) percentile: 1st-25th [Q1, Lp(a) ≤ 14 nmol/L], 26th-50th (Q2, 14-<42 nmol/L), 51st-75th (Q3, 42-<132 nmol/L), and 76th-100th (Q4, 132-855 nmol/L). Outcomes were MACE [composite of cardiovascular (CV) death, myocardial infarction, or coronary revascularization] and MALE (composite of peripheral revascularization, acute limb ischaemia, or major lower extremity amputation). Cox proportional hazard modelling was used to assess the association between Lp(a) and the outcomes of interest after adjusting for traditional risk factors. Among 3757 individuals with PAD [39% female, median age 68 (IQR: 58-77)], individuals with Lp(a) levels in the third and fourth quartiles had a 24 and 30% increased hazard of MACE, respectively [adj. hazard ratio (HR): 1.24, P = 0.005; adj. HR: 1.30, P = 0.001] when compared with those in the first quartile. Individuals in the fourth quartile had a 19% greater hazard of MALE (adj. HR: 1.19, P = 0.043).

CONCLUSION: Elevated Lp(a) in patients with PAD was associated with an increased risk of both MACE and MALE. Accordingly, measurement of Lp(a) may convey important prognostic value and allow for further risk stratification within this high-risk population.

BACKGROUND: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction remains underused. The role of direct-to-physician marketing in accelerating uptake of GDMT is unknown.

OBJECTIVES: The authors investigated the association between industry marketing meals and GDMT prescribing rates under Medicare Part D.

METHODS: The authors linked Medicare data sets to identify general and advanced heart failure (AHF) cardiologists' prescriptions for angiotensin receptor-neprilysin inhibitors (ARNIs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists (MRAs), and beta-blockers from 2019 to 2021. Using negative binomial regression analyses, they examined the association between marketing meals and prescribing rates of marketed and un-marketed classes of GDMT.

RESULTS: Of 11,277 general and 329 AHF cardiologists, 60% received marketing payments for ARNI and 50% for SGLT2i from 2019 to 2021. Among general cardiologists, but not AHF cardiologists, exposure to ARNI marketing meals in 2020 was associated with a greater prescribing volume of ARNI in 2021 (1-4 ARNI meals; relative ratio: 1.43 [95% CI: 1.34-1.53]; 5-9 ARNI meals; relative ratio: 1.69 [95% CI: 1.48-1.93]; ≥10 ARNI meals; relative ratio: 2.09 [95% CI: 1.80-2.43]). Findings were similar for SGLT2i. The association between marketing and prescribing of other pillars of GDMT was inconsistent across drug classes. Neither ARNI nor SGLT2i marketing was consistently associated with increased prescribing of MRAs.

CONCLUSIONS: Industry marketing to general cardiologists is associated with increased uptake of ARNIs and SGLT2is, but not with increased uptake of all pillars of GDMT. Improvements in comprehensive therapy for heart failure will require other mechanisms to accelerate uptake of MRAs and beta-blockers, as well as ARNIs and SGLT2is once multiple generic formulations become available in the United States.