Pulmonary Vein Isolation vs Sham Intervention in Symptomatic Atrial Fibrillation: The SHAM-PVI Randomized Clinical Trial

JAMA 2024 Sep 2:e2417921. doi: 10.1001/jama.2024.17921

Abstract

Importance: There are concerns that pulmonary vein isolation for atrial fibrillation may have a profound placebo effect, but no double-blind randomized clinical trials have been conducted.

Objective: To determine whether pulmonary vein isolation is more effective than a sham procedure for improving outcomes in atrial fibrillation.

Design, setting, and participants: Double-blind randomized clinical trial conducted at 2 tertiary centers in the UK between January 2020 and March 2024 among patients with symptomatic paroxysmal or persistent atrial fibrillation. Major exclusion criteria included long-standing persistent atrial fibrillation, prior left atrium ablation, other arrhythmias requiring ablative therapy, a left atrium of 5.5 cm or larger, and ejection fraction of less than 35%.

Intervention: Participants were randomly assigned to receive pulmonary vein isolation with cryoablation (n = 64) or a sham procedure with phrenic nerve pacing (n = 62).

Main outcomes and measures: The primary end point was atrial fibrillation burden at 6 months, excluding a 3-month blanking period. Secondary outcomes included quality-of-life measures, time to events, and safety. Atrial fibrillation burden was measured by an implantable loop recorder.

Results: A total of 126 participants were randomized (mean age, 66.8 years; 89 men [70.63%]; 20.63% with paroxysmal atrial fibrillation). The absolute mean atrial fibrillation burden change from baseline to 6 months was 60.31% in the ablation group and 35.0% in the sham group (geometric mean difference, 0.25; 95% CI, 0.15-0.42; P < .001). The estimated difference in the overall Atrial Fibrillation Effect on Quality of Life score at 6 months, favoring catheter ablation, was 18.39 points (95% CI, 11.48-25.30 points). The Short Form 36 general health score also improved substantially more with ablation, with an estimated difference of 9.27 points at 6 months (95% CI, 3.78-14.76 points).

Conclusions and relevance: Pulmonary vein isolation resulted in a statistically significant and clinically important decrease in atrial fibrillation burden at 6 months, with substantial improvements in symptoms and quality of life, compared with a sham procedure.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ­­­STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

2024 European Society of Cardiology Guidelines for Management of Elevated BP and Hypertension: Key Points

European Heart Journal, ehae178, https://doi.org/10.1093/eurheartj/ehae178

The key points to remember from the 2024 European Society of Cardiology (ESC) guidelines for the management of elevated blood pressure (BP) and hypertension are:

· The most important point is that the target systolic BP (SBP) for adults receiving BP medications should be 120-129 mm Hg. One can “opt-out” of this goal for patients who cannot tolerate that level of BP, patients who have orthostatic symptoms, patients who are over 85 years old or have frailty, or patients with limited life expectancy. For those patients, the goal is as low a pressure toward that goal as can be achieved.

· Blood Pressure is defined as having a continued risk rooted in time of exposure to higher Blood Pressure. For this reason, hypertension is defined as an systolic BP (SBP) >140 mm Hg or diastolic BP (DBP) >90 mm Hg, but a new category of “elevated BP” has been introduced that is an office systolic BP of 120-139 mm Hg or diastolic BP 70-89 mm Hg. This guideline recognizes that risk increases across this scale, rather than starts at a certain level that is defined as “hypertension.” This category of “elevated BP” reminds us of the term “prehypertension” used in JNC-7 (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure).

· The guideline focuses on true risk reduction related to fatal and nonfatal cardiovascular outcomes. The longstanding tendency of using the surrogate marker of Blood Pressure alone does not support a Class I indication in this guideline, except for lifestyle and low-risk nondrug interventions.

· Out-of-office BP is recommended for diagnostic purposes as it can detect white-coat and masked hypertension. Office measurements can be used when out-of-office readings are not obtainable.

· Lifestyle interventions are recommended for 3 months. If not fully successful, then drug therapy should be started.

· In pregnant women without contraindications and in consultation with an obstetrician, low- to moderate-intensity exercise can reduce the risk of gestational hypertension and pre-eclampsia and should be considered.

· A risk-based approach to hypertension treatment is recommended, noting that those with diabetes, kidney disease, cardiovascular disease, target organ damage, and diabetes of familial hypercholesterolemia are at increased risk for cardiovascular disease. More time and resources should be devoted to patients at higher overall risk from elevated BP.

· Screening for secondary hypertension is recommended for adults diagnosed with hypertension before the age of 40 years, except for obese young adults for whom screening for sleep apnea should be a first step.

· Self-measurement of BP is recognized to improve patient empowerment and adherence to treatment.

· It is recognized that the major weakness of clinical hypertension guidelines is poor implementation. The document includes sections on how to overcome barriers to implementation.

· In patients with atrial fibrillation, manual BPs should be used, as most automated devices have not been validated for BP measurement in patients with atrial fibrillation.

· The guidelines include sex and gender throughout the document. It defines sex as a biological condition of being male or female from conception, based on genes. Gender is a sociocultural dimension of being a man or a woman in a society based on gender roles and norms.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ­­­STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation

DOI: 10.1056/NEJMoa2314328

Background

Whether transcatheter mitral-valve repair improves outcomes in patients with heart failure and functional mitral regurgitation is uncertain.

Methods

We conducted a randomized, controlled trial involving patients with heart failure and moderate to severe functional mitral regurgitation from 30 sites in nine countries. The patients were assigned in a 1:1 ratio to either transcatheter mitral-valve repair and guideline-recommended medical therapy (device group) or medical therapy alone (control group). The three primary end points were the rate of the composite of first or recurrent hospitalization for heart failure or cardiovascular death during 24 months; the rate of first or recurrent hospitalization for heart failure during 24 months; and the change from baseline to 12 months in the score on the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS; scores range from 0 to 100, with higher scores indicating better health status).

Results

A total of 505 patients underwent randomization: 250 were assigned to the device group and 255 to the control group. At 24 months, the rate of first or recurrent hospitalization for heart failure or cardiovascular death was 37.0 events per 100 patient-years in the device group and 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 to 0.85; P=0.002). The rate of first or recurrent hospitalization for heart failure was 26.9 events per 100 patient-years in the device group and 46.6 events per 100 patient-years in the control group (rate ratio, 0.59; 95% CI, 0.42 to 0.82; P=0.002). The KCCQ-OS score increased by a mean (±SD) of 21.6±26.9 points in the device group and 8.0±24.5 points in the control group (mean difference, 10.9 points; 95% CI, 6.8 to 15.0; P<0.001). Device-specific safety events occurred in 4 patients (1.6%).

Conclusions

Among patients with heart failure with moderate to severe functional mitral regurgitation who received medical therapy, the addition of transcatheter mitral-valve repair led to a lower rate of first or recurrent hospitalization for heart failure or cardiovascular death and a lower rate of first or recurrent hospitalization for heart failure at 24 months and better health status at 12 months than medical therapy alone.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ­­­STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

Ticagrelor monotherapy in ST-elevation myocardial infarction: An individual patient-level meta-analysis from TICO and T-PASS trials

Med. 2024 Aug 10:S2666-6340(24)00301-5. doi: 10.1016/j.medj.2024.07.019.

Abstract

Background: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT).

Methods: Individual patient data were pooled from randomized clinical trials that included ST-elevation myocardial infarction STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) short-term dual antiplatelet therapy versus ticagrelor-based 12-month short-term dual antiplatelet therapy DAPT in terms of centrally adjudicated clinical outcomes. The co-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding Academic Research Consortium type 3 or 5 bleeding) at 1 year.

Findings: The pooled cohort contained 2,253 patients with ST-elevation myocardial infarction. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based dual antiplatelet therapy group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%; HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups.

Conclusions: In patients with ST-elevation myocardial infarction treated with drug-eluting stent implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ­­­STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

Efficacy and Safety of P2Y12 monotherapy vs DAPT in patients undergoing percutaneous coronary intervention: meta-analysis of randomized trials

Curr Probl Cardiol. 2024 Aug;49(8):102635. doi: 10.1016/j.cpcardiol.2024.102635

Abstract

Background: Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short dual antiplatelet therapy (DAPT). However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard dual antiplatelet therapy DAPT in patients undergoing percutaneous coronary intervention PCI at 12 months.

Methods: Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definite stent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529).

Results: Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both all cause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard dual antiplatelet therapy DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk of major bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments.

Conclusions: In comparison to standard dual antiplatelet therapy DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ­­­STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

Early postoperative beta-blockers are associated with improved cardiac output after late complete repair of tetralogy of Fallot: a retrospective cohort study

Eur J Pediatr. 2024 Aug;183(8):3309-3317. doi: 10.1007/s00431-024-05597-1.

Abstract

Tetralogy of Fallot is the most common cyanotic congenital heart disease. For decades, our institution has cared for humanitarian patients with late presentation of tetralogy of Fallot. They are characterized by severe right ventricular hypertrophy with consecutive diastolic dysfunction, increasing the risk of postoperative low cardiac output syndrome (LCOS). By right ventricular restrictive physiology, we hypothesized that patients receiving early postoperative beta-blockers (within 48 h after cardiopulmonary bypass) may have better diastolic function and cardiac output. This is a retrospective cohort study in a single-center tertiary pediatric intensive care unit. We included > 1-year-old humanitarian patients with a confirmed diagnosis of tetralogy of Fallot undergoing a complete surgical repair between 2005 and 2019. We measured demographic data, preoperative echocardiographic and cardiac catheterization measures, postoperative mean heart rate, vasoactive-inotropic scores, low cardiac output syndrome scores, length of stay, and mechanical ventilation duration. One hundred sixty-five patients met the inclusion criteria. Fifty-nine patients (36%) received early postoperative beta-blockers, associated with a lower mean heart rate, higher vasoactive-inotropic scores, and lower low cardiac output syndrome scores during the first 48 h following cardiopulmonary bypass. There was no significant difference in lengths of stay and ventilation.

Conclusion: Early postoperative beta-blockers lower the prevalence of postoperative low cardiac output syndrome at the expense of a higher need for vasoactive drugs without any consequence on length of stay and ventilation duration. This approach may benefit the specific population of children undergoing a late complete repair of tetralogy of Fallot.

What is Known: • Prevalence of low cardiac output syndrome is high following a late complete surgical repair of tetralogy of Fallot.

What is New: • Early postoperative beta-blockade is associated with lower heart rate, prolonged relaxation time, and lower prevalence of low cardiac output syndrome. • Negative chronotropic agents like beta-blockers may benefit selected patients undergoing a late complete repair of tetralogy of Fallot, who are numerous in low-income countries.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ­­­STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

Eligibility and Projected Benefits of Rapid Initiation of Quadruple Therapy for Newly Diagnosed Heart Failure

JACC Heart Fail. 2024 Aug;12(8):1365-1377. doi: 10.1016/j.jchf.2024.03.001.

Abstract

Background: U.S. nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized.

Objectives: This study sought to characterize the degree to which patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation.

Methods: Among patients hospitalized for newly diagnosed heart failure with reduced ejection fraction (HFrEF) in the Get With The Guidelines-Heart Failure registry from 2016 to 2023, eligibility criteria based on regulatory labeling, guidelines, and expert consensus documents were applied for angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effects from pivotal clinical trials utilized by the American Heart Association/American College of Cardiology /HFSA Guideline for the Management of Heart Failure, and compared with observed outcomes among patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blockers.

Results: Of 33,036 patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF), 27,158 (82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021 to 2023, of patients eligible for quadruple therapy, 15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-month incidence of mortality was 24.7% and Heart Failure hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number needed to treat = 10) compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker, and 24.8% (number needed to treat = 4) compared with no guideline-directed medical therapy.

Conclusions: In this nationwide U.S. cohort of patients hospitalized for newly diagnosed heart failure with reduced ejection fraction (HFrEF), >4 of 5 patients were projected as eligible for quadruple therapy at discharge; yet, <1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruple medical therapy for newly diagnosed heart failure with reduced ejection fraction (HFrEF) would yield large absolute reductions in mortality.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ­­­STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.