PACUPod: Cardiology

This PACUPod episode reviews Wu et al.'s randomized trial in JAMA Network Open evaluating early cardiac rehabilitation initiated during the CICU for patients with acute decompensated heart failure. In this single-center study of 120 high-risk CICU patients, participants were randomized to an early, progressive, personalized cardiac rehab program during CICU stay (AHF-CR) or to usual care without structured early rehab. Primary outcomes were discharge Short Physical Performance Battery (SPPB) score and six-month all-cause rehospitalization; exploratory outcome included the Perme ICU Mobility score during the CICU stay. Results showed no significant difference in discharge SPPB (median difference 1.0 point; 95% CI crossed zero; p=0.16) or six-month rehospitalization (26.6% vs 28.3%). The rehab group did exhibit improved mobility in the CICU (Perme score median difference 2.76; adjusted p=0.04) and there were no safety concerns. The findings suggest early CICU mobilization is feasible and safe, but restricting rehab to the CICU without post-discharge continuation did not improve discharge function or reduce readmissions. Context with prior rehab literature indicates longer, outpatient or integrated rehab programs (e.g., REHAB-HF) may yield larger functional and clinical benefits, while meta-analyses (Imrpress 2023) show benefits with earlier exercise-based rehab when extended beyond ICU. The episode highlights the importance of rehab timing, duration, and continuity after discharge, as well as multidisciplinary coordination to optimize outcomes for ADHF patients.

In this episode, hosts Britany and Seth unpack the prospective Murcia AF Project III (MAFP-III) cohort study, which investigates remnant cholesterol (RC) and LDL-C discordance as predictors of thromboembolic events in patients with atrial fibrillation on oral anticoagulation. They explain how RC reflects triglyceride-rich lipoproteins (VLDL/IDL), how RC is calculated from standard lipid panels (total cholesterol minus LDL-C minus HDL-C), and the main finding: elevated RC predicts higher thromboembolic risk particularly when LDL-C is low. Over an average follow-up of about 1.86 years, the study reports an adjusted hazard ratio of 1.82 (95% CI 1.03–3.23, p=0.039) for thromboembolic events in the low-LDL-C group, with a linear RC–risk relationship in this subgroup and no similar association for high LDL-C. The episode discusses clinical implications for risk stratification, measurement practicality, and study limitations (observational design, single-center cohort, adherence not fully addressed) and considers future directions for research and potential RC-targeted therapies.

Myocardial bridge (MB) is a common congenital coronary anomaly where a coronary artery tunnels through the myocardium, causing systolic compression. This PACUPod overview examines whether single antiplatelet therapy (APT), such as aspirin, provides ischemic protection for MB patients without other indications, and how the RIALTO registry informs clinical practice. The ambispective study analyzed 221 MB patients after excluding those with established APT or anticoagulation indications, comparing mostly aspirin at discharge versus no APT over a median follow-up of 4.5 years. The primary outcome, net adverse clinical events (NACE), combined cardiovascular death, nonfatal MI, need for coronary imaging, ischemic stroke, and bleeding events. After adjustment for confounders and propensity-matching, single APT was associated with a higher NACE rate (adjusted HR 6.2, p=0.03), chiefly driven by increased minor bleeding (adjusted HR 10.58, p=0.02), with no significant reduction in ischemic events. The findings align with 2019 ACC/AHA primary prevention guidance that cautions aspirin use in the absence of established disease and challenge routine APT in MB patients. The episode discusses MB pathophysiology—ischemia largely results from mechanical compression rather than plaque rupture—and explores management implications, including prioritizing personalized risk assessment, shared decision-making, and careful medication review. Alternatives such as beta-blockers and calcium channel blockers, as well as selective surgical or stenting options for refractory cases, are considered. The role of diagnostic and functional testing (IVUS, OCT, stress imaging) in guiding therapy and avoiding unnecessary APT is highlighted, along with study limitations (observational design, residual confounding) and the need for randomized trials. Related research (e.g., ADAPTT 2023) and the broader context of coronary anomalies are discussed to emphasize individualized care rather than reflexive antiplatelet use.

This PACUPod episode reviews a secondary analysis of the SUMMIT trial investigating how baseline adiposity (BMI and central adiposity via waist-height ratio) and weight loss influence tirzepatide's benefits in obesity-related HFpEF. The discussion covers study design, primary outcome (time to cardiovascular death or worsening heart failure), and secondary outcomes (KCCQ-CSS, six-minute walk distance, CRP, body weight, and systolic blood pressure). Tirzepatide reduced the primary endpoint across all BMI and WHR tertiles, while improvements in functional and inflammatory markers varied with adiposity. Central adiposity identified higher-risk subgroups beyond BMI, and greater weight loss correlated with better 6MWD, quality of life, and reductions in CRP and SBP, suggesting weight loss mediates several benefits. The episode also discusses clinical implications, including targeting central adiposity, dosing considerations, potential pharmacologic interactions, and the need for longer-term data. Future directions include imaging studies to assess remodeling, combination therapy with other HFpEF agents, patient-reported outcomes, precision medicine for responder phenotyping, and cost-effectiveness analyses.

PACULit examines the SOGALDI-PEF trial, the first randomized crossover study comparing dapagliflozin alone versus dapagliflozin plus spironolactone in heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). The episode discusses the rationale for combining an SGLT2 inhibitor with a mineralocorticoid receptor antagonist, the primary NT-proBNP endpoint as a surrogate for cardiac stress, and key results showing an approximate 11% relative reduction in NT-proBNP with combination therapy, along with reductions in systolic blood pressure and urinary albumin-to-creatinine ratio, but with greater eGFR decline and higher potassium-related safety concerns. Design features (108 patients, 12-week treatment periods per arm, open-label with blinded endpoints) and limitations (short duration, small sample, lack of hard outcomes) are explored, as are clinical implications for balancing potential efficacy with risks of hyperkalemia and renal dysfunction. The episode emphasizes the need for careful patient selection, monitoring, and larger, longer trials to confirm hard outcomes in HFpEF/HFmrEF.

This PACUPod episode summarizes Barry et al.'s population-based cohort study on the impact of post-CABG P2Y12 inhibitors (primarily clopidogrel) on major adverse cardiovascular events. Using data from British Columbia (2002–2020) involving over 15,000 adults undergoing isolated CABG, exposure was defined as filling a P2Y12 inhibitor prescription within 30 days after surgery, compared with aspirin alone or no antiplatelet therapy. The primary outcome was time to first MACE (all-cause death, nonfatal MI, or nonfatal ischemic stroke) with up to five years of follow-up, and secondary outcomes included individual MACE components and an extended MACE definition. Inverse probability treatment weighting was employed to adjust for confounders. Results showed a 61% relative reduction in MACE risk at one year (hazard ratio 0.39; 95% CI 0.27–0.55) and a sustained ~35% reduction at five years, along with lower hazards for all-cause and cardiovascular death and the extended MACE outcome. Adherence, as measured by proportion of days covered, did not significantly modify outcomes, suggesting early initiation post-CABG is key. The episode discusses clinical implications for routine early initiation of P2Y12 inhibitors (mainly clopidogrel) in combination with aspirin, the need for multidisciplinary coordination to balance ischemic protection with bleeding risk, and remaining knowledge gaps about optimal duration and comparisons with other P2Y12 inhibitors. Limitations include the observational design, residual confounding, and exposure based on prescription fills rather than confirmed ingestion.

A concise overview of a prospective controlled cohort study assessing whether adding low-dose colchicine (0.5 mg daily) to stable vitamin K antagonist (VKA) therapy in adults with chronic coronary disease affects anticoagulation control. Primary outcome: INR changes; secondary outcomes: VKA dose adjustments and time in therapeutic range (TTR). Findings: initiation, continuation, or withdrawal of low-dose colchicine did not significantly alter INR, VKA dosing, or TTR, supporting safe coadministration without additional INR monitoring beyond standard care. Limitations include short follow-up, exclusion of unstable disease and severe renal/hepatic impairment, and lack of formal safety assessment for bleeding or thrombosis. Clinical implications: aligns with existing guidelines and suggests simpler anticoagulation management when colchicine is added in stable patients, though vigilance during early use and consideration of polypharmacy remain important. Future research: longer-term studies and evaluation in special populations, including those with renal impairment or on multiple interacting drugs.

This PACULit episode reviews the PRAGUE-25 randomized multicenter noninferiority trial comparing catheter ablation with lifestyle modification plus guideline-directed antiarrhythmic drugs in adults with obesity (BMI 30–40) and paroxysmal or persistent atrial fibrillation. The ablation strategy focused on pulmonary vein isolation, while the lifestyle arm emphasized weight loss and physical activity paired with antiarrhythmic therapy. The primary endpoint—freedom from AF at 12 months (no episodes >30 seconds on a 7-day Holter)—favored ablation (73% vs 34.6%, p<0.001). Although the lifestyle-plus-drug approach achieved meaningful metabolic gains (average weight loss ~6.4 kg and HbA1c improvement), it did not translate into superior rhythm control. Follow-up averaged ~23.5 months with quarterly rhythm monitoring. The study supports catheter ablation as the preferred rhythm-control strategy in obese AF patients when rhythm suppression is the goal, while lifestyle modification remains important for metabolic risk reduction. Strengths include randomized multicenter design and objective rhythm monitoring; limitations include the 12-month primary endpoint and applicability to patients with more severe comorbidities.

This PACULit update summarizes a single-center, prospective observational study (ChangZhou Registry) evaluating whether initiating dapagliflozin during hospitalization for acute myocardial infarction reduces malignant ventricular arrhythmias in elderly patients and affects all-cause mortality over about seven months. In 2,607 patients aged 60 and older with confirmed AMI, those treated with dapagliflozin were compared to standard care using propensity score matching. The primary outcome was malignant ventricular arrhythmias during hospitalization; the secondary outcome was all-cause mortality (median ~211 days). Results showed malignant ventricular arrhythmias occurred in 2.2% of the dapagliflozin group versus 5.1% in controls, with odds ratios around 0.34 after matching (roughly 60–65% risk reduction). All-cause mortality was also significantly lower in the dapagliflozin group (p = 0.033). The discussion highlights potential mechanisms for antiarrhythmic effects, including improved myocardial metabolism, reduced fibrosis, ion-channel modulation, and attenuated sympathetic activity. Limitations include its single-center, observational design and potential residual confounding, limiting generalizability. The findings suggest potential benefits of early post-AMI dapagliflozin initiation in elderly patients at high arrhythmia risk and align with broader SGLT2 inhibitor cardiovascular effects, while underscoring the need for multicenter randomized trials focused on malignant ventricular arrhythmias.

This PACULit episode reviews a large observational cohort study by Aebi et al. using UK CPRD data (2000–2021) to compare new monotherapy users of amlodipine, ramipril, and bendroflūmethylthiazide (bendroflumethiazide) and to assess risk of acute outpatient infections (respiratory, genitourinary, gastrointestinal, sepsis) and SARS-CoV-2 infection during 2020–2021. The primary comparisons were amlodipine versus ramipril and amlodipine versus bendroflumethiazide, with follow-up from prescription start to infection, censoring, or study end. Propensity score weighting balanced baseline covariates, and the study excluded individuals with prior cardiovascular disease to reduce confounding. Findings showed lower infection incidence among amlodipine users (IRR 0.77 vs ramipril; 0.78 vs bendroflumethiazide; infections per 1,000 person-years: 38.9 vs 51.6). During the COVID-19 period, amlodipine was associated with a 43% reduced risk of diagnosed SARS-CoV-2 infection (IRR 0.57). The discussion notes potential immunomodulatory and anti-inflammatory mechanisms, cites in vitro and endothelial studies, and acknowledges limitations inherent to observational designs (residual confounding, potential misclassification, and lack of randomized causality). Implications suggest considering possible infection-related benefits when initiating antihypertensive therapy, while emphasizing the need for randomized trials to confirm causality and assess broader outcomes.

A concise episode summarizing a post hoc analysis of the STEP trial that investigates how baseline cardiovascular risk modifies the balance of benefits and harms of intensive blood pressure control in older hypertensive adults. We cover study design, key findings (overall reduction in cardiovascular events with intensive targets, modest non-significant rise in adverse events), risk-stratified results, practical targets (110–130 mm Hg vs 130–150 mm Hg), and implications for practice in acute, critical, and chronic care—with emphasis on individualized therapy and vigilant monitoring.

In this PACUPod episode, we review a pragmatic, cluster-randomized trial evaluating AI-assisted interpretation of standard 12-lead ECGs to identify atrial fibrillation and prompt guideline-directed oral anticoagulant therapy in hospitalized patients managed by non-cardiologists across two Taiwanese hospitals. The AI sends alerts with actionable recommendations to consider AF diagnosis and initiate NOACs. Primary outcomes include NOAC prescription within 90 days post-discharge, new AF diagnoses, echocardiography orders, and cardiologist referrals; secondary outcomes cover ischemic stroke, cardiovascular death, and all-cause mortality. Results show a significant increase in NOAC initiation (23.3% vs 12.0%; HR 1.85) and new AF diagnoses (HR 1.40) in the AI-alert group, with no significant differences in imaging or referrals or short-term clinical outcomes. The episode discusses the implications for real-world hospital workflows, the potential to close the AF treatment gap, and the need for longer follow-up, while situating findings within prior AI AF detection research and emphasizing multidisciplinary collaboration to optimize stroke prevention through timely anticoagulation.

This PACULit episode reviews a phase 3, randomized, open-label multicenter trial evaluating edoxaban started within three months after surgical bioprosthetic valve replacement (aortic and/or mitral) compared with warfarin. The primary outcome was stroke or systemic embolism; edoxaban showed 0.5% vs 1.5% in warfarin with a risk difference of −1.03% (95% CI −4.34% to 1.95%), indicating comparable efficacy. Major bleeding was higher with edoxaban (4.1% vs 1.0%; risk difference 3.07%, 95% CI −0.67% to 7.27%). Intracardiac thrombus occurred only with warfarin (1.0%), while none were observed with edoxaban. Dosing adjustments were based on renal function and weight; edoxaban offers fixed dosing without routine INR monitoring and is a substrate of P-glycoprotein. Limitations include open-label design, short follow-up, and low event rates. Implications emphasize patient-specific thrombotic risk, valve position, and bleeding risk when choosing between DOACs and VKAs post-bioprosthetic valve surgery, with considerations of cost and adherence. Related analyses and ongoing data suggest DOACs may be viable alternatives, warranting individualized assessment.

In this PACUPod episode, the study by Augustine et al. on pharmacist-led transitions of care (TOC) after hospitalization for acute myocardial infarction (AMI) is examined. The real-world, single-center pre-post design compares outcomes before and after implementing a TOC service focused on medication reconciliation, patient education, and discharge optimization. The primary outcome was 90-day cardiovascular readmissions; secondary outcomes included 30-day cardiovascular and all-cause readmissions and discharge on defect-free guideline-directed medical therapy (GDMT). Results showed no significant reduction in 90-day cardiovascular readmissions (10.7% pre-TOC vs 9.9% post-TOC; OR 0.937, p=0.842). However, discharge on defect-free GDMT improved markedly from 61.5% to 87.7% (OR 5.424, p<0.001), highlighting a substantial process improvement even when short-term clinical outcomes did not change. Limitations include lack of randomization, use of historical controls, and absence of confounding adjustments, which limit generalizability. The episode discusses the implications of improved GDMT adherence, the essential role of medication reconciliation and patient education in TOC, and the need for outpatient follow-up and adherence monitoring to translate process gains into long-term clinical benefits. Looking ahead, the evidence suggests the value of larger multicenter randomized trials that incorporate outpatient adherence and patient-reported outcomes to better define the impact on readmissions and cardiovascular health.