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.

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.

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: 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.

BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) levels are a leading risk factor for atherosclerotic cardiovascular disease (ASCVD), a major global cause of illness and death. Patients' qualitative insights about experiences, priorities, and needs are essential for creating more targeted, patient-centered quality improvement interventions.

OBJECTIVES: To document the experiences of people with high levels of low-density LDL-C in three countries.

METHODS: Qualitative study of 60-min in-depth interviews with 50 adult patients from Australia, Brazil, and the United States. The study was overseen by a Steering Committee comprising patients, patient advocates, researchers, and cardiologists. The interviews explored pathways and barriers to high LDL-C diagnosis; the burden of managing high LDL-C and the awareness of the association between high LDL-C and cardiovascular risks. The data were analyzed by applying a structured, team-based approach to coding qualitative data.

RESULTS: There were three main pathways to diagnosing high cholesterol: routine physical exams conducted by primary care providers; symptomatic presentations or incidental findings during emergency visits and through a healthcare visit for another condition, frequently diabetes. Healthcare providers' communication styles influenced patients' perceptions of their conditions. Two-thirds of participants (n = 33) attempted lifestyle changes after their high cholesterol diagnosis, but work schedules and daily routines posed barriers to maintaining healthy habits. Some participants who experienced ASCVD events waited hours or days before seeking care, assuming their symptoms were not serious. After diagnosis of an ASCVD event, many patients feared death and worried about their families' futures. When asked about potential improvements to their current therapy, 21 patients mentioned reduced administration frequency.

CONCLUSIONS: This pilot study provides insights into patients' experiences living with and managing elevated LDL-C. It describes opportunities for policymakers and healthcare providers to improve the detection of elevated LDL-C and support patients in understanding risks and strategies for reducing the risk of ASCVD events.