Publications

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: 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.

BACKGROUND: Prompt revascularization is crucial for managing for chronic limb-threatening ischemia (CLTI), but disparities in socioeconomic status (SES) and healthcare access affect outcomes. The COVID-19 pandemic exacerbated these inequities, yet their impact on CLTI outcomes remains underexplored.

OBJECTIVE: 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 pre-pandemic (1/1/2016-3/31/2020), pandemic (3/31/2020-12/31/2021), and late-pandemic (12/31/2021-12/31/2023). Metrics were evaluated pre- and post-revascularization. Endpoints 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 (HR 1.04 [1.03-1.05], p<0.001). These disparities persisted across the entire study period, including pre-, during-, and post-pandemic eras. Pre-pandemic, risks were elevated (HR 1.01 [1.00-1.03], p=0.125), worsening during the pandemic (HR 1.06 [1.03-1.09], p<0.001) and late-pandemic (HR 1.07 [1.03-1.11], p<0.001). The proportion of percutaneous vascular interventions (PVIs) in distressed communities declined annually (-0.59% [-0.68% to -0.50%], p<0.0001). These patients had fewer vascular visits (pre: 5.62 vs. 6.63; post: 6.52 vs. 7.57; p<0.001) but more ED visits (0.04 vs. 0.03; p<0.001) and hospital readmissions (0.13 vs. 0.11; p<0.001).

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

BACKGROUND: Racial differences in the use and outcomes of intravascular imaging (IVI) and invasive physiology (IP) during percutaneous coronary intervention (PCI) are underreported in the United States.

METHODS: Medicare fee-for-service claims data were used to examine the use and outcomes of IVI- and IP-guided PCI by Black versus White race (2016-2023). Multivariable logistic regression was used to assess the association between race and IVI/IP use. The primary outcome was major adverse cardiovascular events, which included myocardial infarction, repeat revascularization, and death. Outcomes were compared by race according to the device used (IVI versus none; IP versus none; and among all IVI/IP recipients). Cox regression was used to estimate the association between race and 2-year outcomes, adjusting for all baseline characteristics.

RESULTS: The study included 1 481 343 PCI patients (5.9% Black, 63.6% male, mean age 75.3±7.0 years). IVI was used in 17.6% of PCIs in White patients and 15.0% in Black patients; IP use was 7.1% and 5.7%, respectively. After adjustment, Black adults were less likely to receive IVI (odds ratio, 0.94 [95% CI, 0.93-0.96]) or IP (odds ratio, 0.83 [95% CI, 0.81-0.85]). IVI- and IP-guided PCI had lower major adverse cardiovascular event risk at 2-years in both racial groups compared with angiography alone: IVI (White: hazard ratio [HR], 0.93 [95% CI, 0.92-0.94]; Black: HR, 0.85 [95% CI, 0.84-0.87]) and IP (White: HR, 0.95 [95% CI, 0.92-0.98]); Black: HR, 0.87 [95% CI, 0.83-0.91]). However, despite global benefits with IVI/IP, Black adults had a higher adjusted risk of major adverse cardiovascular events compared with White adults (HR, 1.02 [95% CI, 1.01-1.03]).

CONCLUSIONS: IVI- and IP-guided PCI were associated with improved outcomes in both Black and White beneficiaries, yet these technologies were less frequently used in Black adults, and overall PCI outcomes remained worse for this group.

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 (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.

This report describes a novel technique using intravascular ultrasound (IVUS) to guide revascularization of a stumpless posterior tibial artery occlusion in a patient with chronic limb-threatening ischemia. After failed attempts at both antegrade and retrograde access, IVUS was employed to identify and mark the exact location of the posterior tibial artery ostium. Using this guidance, successful wire cannulation was achieved, confirmed intraluminally with IVUS, followed by balloon angioplasty and restoration of brisk in-line flow through the posterior tibial and lateral plantar arteries. This intervention ultimately led to complete wound healing and avoided a major amputation. In conclusion, this IVUS-guided technique offers a safe and effective approach for revascularizing challenging stumpless tibial occlusions, expanding the tools available for limb salvage in complex peripheral artery disease.