Cardiology

Torsemide vs. Furosemide After Hospitalization for Heart Failure

Posted by

0


Results of a large clinical trial counter previous findings of benefit with torsemide.

Several small studies have suggested that the loop diuretic torsemide produces better outcomes than the more commonly used furosemide in patients with heart failure. However, the two agents have never been directly compared in a major clinical trial despite potentially important differences in their bioavailability and other properties. Now, investigators for the TRANSFORM-HF trial (NCT03296813. opens in new tab) report similar 1-year outcomes with use of torsemide versus furosemide in this setting.

In this open-label, pragmatic, multicenter trial, 2859 participants hospitalized for heart failure were randomized to receive torsemide or furosemide. Recruited patients had treatment plans indicating anticipated long-term use of a loop diuretic. The primary outcome was all-cause mortality in a time-to-event analysis. A key secondary outcome was all-cause mortality or all-cause hospitalization assessed over 12 months. Results included the following:

  • 12-month death rates of 26.1% in the torsemide group and 26.2% in the furosemide group
  • Death or hospitalization in 47.3% and 49.3%, respectively
  • A 7% crossover rate from torsemide to furosemide and a 3.8% crossover rate the other way

The authors noted that loss to follow-up and participant crossover and nonadherence were key limitations.

Comment

This study provides evidence that there is little to choose between furosemide and torsemide. As a pragmatic trial, it had broad entry criteria and included people with a range of ejection fractions, which may be good for generalizability, although an editorialist notes challenges in assessing whether there were important differences in subgroups. Also, the trial enrolled fewer patients than planned, reducing the power of subgroup analyses. Nevertheless, it is a solid counterweight to the small and observational studies that noted an immense benefit with torsemide.

Apixaban for Stroke Prevention in

Posted by

0


Abstract

Background

Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit.

Methods

We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason).

Results

We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P=0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P=0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group.

Conclusions

Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding.

Clonal Hematopoiesis and Cardiovascular Disease in Patients With Multiple Myeloma Undergoing Hematopoietic Cell Transplant

Posted by

0


Abstract

Importance  There is a paucity of information on the association between clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular disease (CVD) in patients with cancer, including those with multiple myeloma (MM) undergoing hematopoietic cell transplant (HCT), a population at high risk of developing CVD after HCT.

Objective  To examine the association between CHIP and CVD in patients with MM and to describe modifiers of CVD risk among those with CHIP.

Design, Setting, and Participants  This was a retrospective cohort study of patients with MM who underwent HCT between 2010 and 2016 at City of Hope Comprehensive Cancer Center in Duarte, California, and had pre-HCT mobilized peripheral blood stem cell (PBSC) products cryopreserved and accessible for CHIP analyses. The study team performed targeted panel DNA sequencing to detect the presence of CHIP (variant allele frequency 2% or more).

Main Outcomes and Measures  The primary end point was the 5-year cumulative incidence and risk for developing de novo CVD (heart failure, coronary artery disease, or stroke) after HCT.

Results  Of 1036 consecutive patients with MM (580 male [56%]; median age, 60.0 years) who underwent a first autologous HCT, 201 patients had at least 1 CHIP variant (19.4%) and 35 patients had 2 or more variants (3.4%). The 5-year incidence of CVD was significantly higher in patients with CHIP (21.1% vs 8.4%; P < .001) compared with those without CHIP; the 5-year incidence among those with 2 or more variants was 25.6%. In the multivariable model, CHIP was associated with increased risk of CVD (hazard ratio [HR], 2.72; 95% CI, 1.70-4.39), as well as of individual outcomes of interest, including heart failure (HR, 4.02; 95% CI, 2.32-6.98), coronary artery disease (HR, 2.22; 95% CI, 1.06-4.63), and stroke (HR, 3.02; 95% CI, 1.07-8.52). Patients who had both CHIP and preexisting hypertension or dyslipidemia were at nearly 7-fold and 4-fold increased risk of CVD, respectively (reference: no CHIP, no hypertension, or dyslipidemia).

Conclusion and Relevance  CHIP was significantly and independently associated with risk of CVD in patients with MM undergoing HCT and may serve as a novel biologically plausible biomarker for CVD in this cohort. Patients with MM and both CHIP and cardiovascular risk factors had an exceptionally high risk of CVD. Additional studies are warranted to determine if cardiovascular preventive measures can reduce CHIP-associated CVD risk.

Introduction

Autologous hematopoietic cell transplant (HCT) is an effective treatment for patients with multiple myeloma (MM), especially for individuals who are medically fit and demonstrate disease response to induction therapy.1,2 In fact, MM is the most common indication for autologous HCT, with more than 7000 patients undergoing transplant annually in the US alone.3 Research into survivorship issues during the past 2 decades has highlighted the high risk for developing cardiovascular disease (CVD) following autologous HCT, especially among patients with lymphoma attributed to pre-HCT exposures to cardiotoxic chemotherapies, HCT-associated conditioning exposures, and de novo modifiable cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia) that emerge after HCT.4–6 Yet, there is a paucity of information on the risk of CVD after HCT7 for patients with MM, including the role of emerging biologic modifiers of CVD risk in the general population.

Clonal hematopoiesis of indeterminate potential (CHIP) refers to clonal expansion of blood cells driven by somatic leukemogenic variants in otherwise healthy or patients or individuals without leukemia.8 In nononcology populations, CHIP has been associated with aging-related health conditions, including coronary artery disease (CAD),9,10 heart failure,11 and stroke.12 Accumulating data suggest CHIP is more prevalent in patients with cancer after cancer treatment exposures compared with age-matched controls, attributed in part to clonal selection that results from myelotoxic stressors.13

Despite the growing body of literature on the risk of CVD associated with CHIP in nononcology populations, there is limited information on the association between CHIP and CVD risk among patients with cancer, a population with high rates of CHIP that may be driven by the cancer itself, associated comorbidities, or cancer treatment exposures. Therefore, we examined the association between pre-HCT CHIP and CVD after HCT in a demographically diverse population of patients with MM and further explored the interaction between modifiable cardiovascular risk factors at the time of HCT and CHIP on long-term cardiovascular outcomes.

Discussion

In this study, leveraging a large, well-characterized, and demographically diverse cohort of patients with MM undergoing autologous HCT with available pre-HCT DNA, we found that CHIP was highly prevalent and associated with a significantly higher incidence of CVD after HCT compared with those without CHIP. In the adjusted model, CHIP was associated with a nearly 3-fold risk of developing any CVD and this association remained consistent by CVD subtype. The incidence of CVD after HCT was highest in patients with CHIP and hypertension or dyslipidemia (30% each), corresponding to nearly 7-fold and 4-fold increased risk of CVD, respectively, compared with those without CHIP and these modifiable risk factors. The findings from this study highlight the potential role of pre-HCT CHIP as a novel biomarker to better define CVD risk in patients with MM prior to HCT.

The current study is in line with the growing body of literature demonstrating that CHIP is a commonly occurring somatic mutation in patients with cancer exposed to cytotoxic therapies,25,26 given that all patients had received induction treatment prior to referral to HCT. That said, the associations between HCT-CI (comorbidity burden),27 complete remission status, and CHIP are unique. The association between high HCT-CI score and CHIP may be explained, in part, by the chronic proinflammatory state attributed to underlying comorbidities, an association also reported in patients living with HIV28 or those who develop premature menopause due to chronic illness.29 The association between complete remission status and CHIP may be attributed to a higher disease burden at HCT and associated challenges of maintaining durable response prior to HCT.

The presence of CHIP prior to HCT was significantly and independently associated with increased risk of de novo heart failure, CAD, stroke, as well as composite CVD. Sensitivity analysis censoring follow-up at the time of relapse/recurrence further confirmed these associations. There was also a graded association between the number of CHIP variants and incidence of CVD, suggesting a dose-dependent and additive effect. Variants in ASXL1 were most significantly associated with risk of CVD. We speculate this association may be driven in part by that the high (more than 50%) proportion of CVD cases that were heart failure. ASXL1 has been previously identified as uniquely associated with risk of having reduced left ventricular ejection fraction in a large nononcology population-based CHIP study11 and there is preclinical evidence to suggest a potential causative relationship between ASXL1-mediated clonal hematopoiesis and heart failure.30

Despite the strong association between CHIP and CVD, to our knowledge, to date, there are no CHIP-targeted interventions to modulate the associated CVD risk. Modifiable risk factors, such as hypertension, diabetes, and dyslipidemia, are established targets for CVD risk reduction in the general population but have not been studied in the context of CHIP. While there was no statistically significant interaction between these risk factors and CHIP, we believe our combined analyses reflect clinically meaningful subgroups of patients with MM. In our study, patients with CHIP and hypertension had nearly 7-fold risk of developing CVD and the risk was nearly 4-fold in patients with CHIP and dyslipidemia, compared with patients without CHIP and these individual risk factors. These results underscore the exceedingly high risk of CVD in the subset of patients with MM who have both CHIP and modifiable CVD risk factors, which may provide the rationale for resource allocation to develop more personalized interventions, such as early screening and treatment of these modifiable risk factors (eg, intensive blood pressure control and lipid-lowering strategies),31 in coordination with cardiologists to decrease the morbidity and mortality associated with CVD after HCT.

Conclusions

In summary, we demonstrate a significant association between CHIP and incident CVD after HCT in patients with MM, with the strongest association noted among patients undergoing HCT with modifiable risk factors, such as hypertension and diabetes. These findings may inform more targeted approaches to screening for CVD risk, allowing for improved CVD risk prediction prior to HCT and to guide the implementation of personalized preventive measures to improve health outcomes in at-risk patients. Additional studies are needed to further delineate if the association between CHIP and CVD exists in other cancer populations (eg, solid tumors, nonleukemic hematologic cancers) and to interrogate the specific gene-environment interactions that modulate long-term CVD risk.

Exercise ECGs Highly Specific for Coronary Microvascular Dysfunction

Posted by

0


Reconsidering the humble testing modality’s false-positive issue

A photo of a mature woman riding an exercise bicycle while connected to leads during a cardiac stress test.

Exercise electrocardiographic (ECG) stress tests appeared to reliably indicate that some patients with angina with nonobstructive coronary arteries (ANOCA) actually had coronary microvascular dysfunction (CMD), preliminary evidence showed.

A standard Bruce-protocol exercise test showed 100% specificity for CMD, verified against invasive coronary assessment as reference, with all patients showing ischemic ECG changes during the exercise test also having confirmed CMD. Using endothelium-independent and endothelium-dependent CMD as the reference standard, the false-positive rate of the exercise tests was 0% in a small cohort, reported Haseeb Rahman, PhD, BMBCh, of St. Thomas’ Hospital in London, and colleagues.

Therefore, with these basic exercise tests, patients with ANOCA could be provided with an explanation for their symptoms and a mechanism for myocardial ischemia in the absence of obstructive disease.

“In patients with ANOCA, ischemia on EST [exercise ECG stress testing] was highly specific of an underlying ischemic substrate. These findings challenge the traditional belief that EST has a high false-positive rate,” Rahman’s group concluded in the Journal of the American College of Cardiologyopens in a new tab or window.

A simple noninvasive testing modality, exercise ECG stress testing has fallen out of favor in recent years due to frequent false positives when used for detecting obstructive coronary artery disease (CAD) as validated against visual diameter stenosis on coronary angiography.

“However, we now know that myocardial ischemia can, and indeed in nearly one-third of cases does, occur in the absence of obstructive CAD due to CMD. Therefore, it is conceivable that historical false-positive EST results were due not to the poor specificity of EST as a diagnostic test but rather to the limitations of obstructive CAD as a reference standard for myocardial ischemia,” the study authors explained.

“Our results show that a positive result on EST is highly specific for (and suggestive of) the presence of an ischemic substrate, but as this does not distinguish the relative contributions of the epicardial and microvascular compartments, EST will always have to be combined with a test that specifically evaluates the epicardial coronary arteries, namely, invasive or noninvasive coronary angiography,” they added.

The London group suggested keeping coronary CT angiography as the first-line assessment for patients presenting with chest pain that might be consistent with inducible ischemia. The exercise ECG would be a second-line test “to expedite the diagnosis of CMD in a large proportion of patients and streamline the use of (less widely available and more costly) tests, such as invasive physiology and/or stress perfusion cardiac [MRI].”

Whether this strategy works would need further testing, the researchers acknowledged.

“This proposed approach requires further studies to assess its utility in clinical practice, as ANOCA may also arise from epicardial coronary artery spasm, which was not addressed in the present study,” wrote a trio led by John Beltrame, BMBS, PhD, of the University of Adelaide in Australia, in an accompanying editorialopens in a new tab or window.

“As with any diagnostic investigation, the clinician must address the purpose for undertaking an investigation in each patient. If the clinical question is to identify the presence of obstructive CAD, then clearly CT coronary angiography is the optimal noninvasive technique,” the group wrote. “In contrast, the EST is not designed to assess coronary artery anatomy but is a simple, inexpensive, noninvasive technique to detect the presence of myocardial ischemia in appropriate patients.”

In this study, Rahman’s team made the case for exercise testing with a cohort of consecutive patients presenting with angina who were referred for further assessment. There were 262 individuals with stable angina screened for eligibility, of whom 160 made it to coronary angiography with physiological assessment and 102 who were ultimately included in the final analysis. Inclusion criteria included ANOCA (fractional flow reserve >0.80) and preserved left ventricular ejection fraction (>50%). The final cohort had a mean age of 60 years, and 65% were women.

Participants underwent exercise stress tests a median 29 days after invasive coronary angiography with physiological assessment using adenosine and acetylcholine.

All 32 patients who developed ischemia during testing had CMD, while their 70 nonischemic peers had CMD in 66% of cases (P<0.001).

The ischemic group tended to have lower acetylcholine flow reserve (AChFR), indicating endothelium-dependent microvascular dysfunction. AChFR ≤1.5 — not coronary flow reserve — was the strongest predictor of ischemic ECG changes during exercise.

“This reiterates the physiological relevance of acetylcholine testing in the evaluation of patients with ANOCA … [AChFR] is likely to be a better surrogate for the physiological flow-mediated vasodilatation that occurs during exercise, as it assesses the functionality of both the endothelial and vascular smooth muscle pathways,” Rahman and colleagues stressed.

They nevertheless acknowledged that their observations were based on a single-center study with a relatively small sample size, and may not apply to patients without angina symptoms.

Unraveling Wavy ST Segments—An Unusual Case of Syncope

Posted by

0


Case Presentation

A patient in their 60s with gastroesophageal reflex disease (GERD) presented to the emergency department after loss of consciousness during dinner. They described a prodrome of lightheadedness before they fell to the floor and sustained a head strike. The patient reported episodes of daily intermittent chest discomfort occurring at rest over the prior 2 months, most often in the afternoons, which they attributed to GERD. On presentation, the patient’s heart rate was 59 beats/min, and blood pressure was 130/90 mm Hg. Orthostatic vital signs were negative. Cardiopulmonary and neurological examination findings were normal. Laboratory values, including high-sensitivity troponin and electrolytes, were within normal limits. The initial electrocardiogram (ECG) showed sinus rhythm with no evidence of epsilon waves, Brugada pattern, early repolarization, or long or short QT intervals. The patient was admitted for workup of syncope and underwent cardiac telemetry monitoring. On hospital day 2, the patient experienced the usual chest discomfort while resting in bed; loss of consciousness did not occur. Physical examination findings, stat high-sensitivity troponin level, and electrolytes were all normal. The patient’s chest discomfort resolved within 5 minutes of onset. A transthoracic echocardiogram showed no underlying structural or valvular disease. Telemetry strips from around the time of this episode are shown in the Figure.

Continuously Recorded Cardiac Telemetry

A, Lead II cardiac telemetry shows onset of ischemic episode (arrowhead). B, Progressively increasing ST-segment elevation. C, ST-segment elevation leads to monomorphic ventricular tachycardia. D, Spontaneous termination of monomorphic ventricular tachycardia. Resulting rhythm with residual T-wave inversions.

Questions: What are the notable findings on the lead II telemetry strips? What are the next steps in diagnostic evaluation? What is the appropriate management for this patient?

Interpretation

Lead II telemetry data show the onset of ischemic changes with progressive ST-segment elevation (STE) over the subsequent 60 seconds (Figure, A-B), followed by resolution (Figure, C-D). A monomorphic wide complex tachycardia occurs (Figure, C), with an increase in rate (warm-up phenomenon) and subsequent decrease (warm-down phenomenon; Figure, D), suggesting automaticity from a focal ventricular tachycardia (VT) origin.1

Clinical Course

The patient was started on intravenous amiodarone therapy for presumed nonsustained VT (NSVT) as a cause of the syncope. In light of clinical stability, lack of additional episodes of NSVT, and normal 12-lead ECG and laboratory study results, the patient underwent left-sided heart catheterization the following morning, which showed nonobstructive coronary artery disease (30% stenosis of the right coronary artery). Given normal coronary artery angiogram and telemetry strips documenting myocardial ischemia, the patient was diagnosed with coronary artery vasospasm. Amiodarone treatment was discontinued, and oral diltiazem treatment was begun. The patient was discharged with a wearable cardioverter defibrillator (LifeVest; ZOLL Medical Corporation) and a 2-week ambulatory ECG monitor. Over the subsequent follow-up, the patient had no recurrent episodes of STE or NSVT on ambulatory monitoring.

Discussion

Coronary artery vasospasm is characterized by abnormal vasoconstriction of the coronary arteries leading to myocardial ischemia.2 It was first described as a “variant” angina by Prinzmetal et al3 in the 1950s and further defined by Maseri et al4 in the 1970s. Coronary artery vasospasm often occurs as chest pain at rest, more commonly in young patients without coronary artery disease, and late at night or early in the morning. Patients can experience symptoms such as diaphoresis, nausea, vomiting, and palpitations; however, almost two-thirds of patients present with asymptomatic myocardial ischemia.2 Interestingly, the current patient presented with mid-afternoon chest discomfort, as well as postprandial syncope.

Ischemia due to coronary artery vasospasm can range from subendothelial to transmural, which corresponds to ST-segment depression and STE on ECG, respectively. STE may trigger various arrhythmias, specifically bradyarrhythmias (ie, sinus node dysfunction, atrioventricular block) and ventricular tachycardia/fibrillation (VT/VF). VT may present as chest pain, palpitations, lightheadedness, syncope, and sudden death. Arrhythmias are the common causes of cardiac syncope, accounting for up to 14% of all patients with syncope.5 Nakamura et al6 reported that 10% to 20% of patients with coronary artery vasospasm present with clinically significant arrhythmias, including VT/VF or high-degree atrioventricular block.

Cardiac telemetry can be helpful to detect ischemia when not captured on a 12-lead ECG, to facilitate diagnosis and management strategies.7 While history, telemetry, and ambulatory ECG monitoring can raise suspicion for coronary artery vasospasm, provocative testing with intracoronary acetylcholine during coronary artery angiography is the gold standard for diagnosis.8,9 Intracoronary acetylcholine initially causes coronary artery vasodilation via binding to endothelium-derived relaxing factor followed by reflex sympathetic discharge and subsequent α-adrenergic–mediated coronary artery constriction.10 Intracoronary acetylcholine provocation testing was not available during coronary artery angiography in the current patient. Calcium channel blockers are the preferred pharmacologic treatment for coronary artery vasospasm because they cause vasodilation by inhibiting influx of Ca2+ into coronary smooth muscle cells. Nitrates are also effective, as they promote nitric oxide release, which causes subsequent vasodilation.

Take-Home Points

  • Coronary artery vasospasm is transient myocardial ischemia and can progress to high-risk ventricular arrhythmias and sudden death; high-risk patients require diltiazem treatment indefinitely.
  • Continuous ST-segment monitoring in hospitalized patients is reasonable in coronary artery vasospasm to capture onset and offset of ischemia and until symptoms resolve.
  • Ambulatory ECG monitoring with high fidelity for detecting ST-segment changes and response to oral therapy is essential for follow-up in review of further STE and evidence of myocardial ischemia.

Window for Post-Stroke Antiplatelet Therapy Can Be Extended

Posted by

0


Combined clopidogrel and aspirin initiated within 72 hours of a stroke is associated with a lower risk for a new stroke at 90 days but has a higher risk for moderate to severe bleeding than aspirin alone, new results of a randomized trial showed, suggesting treatment can be given past the current 24-hour time window for the use of dual antiplatelet therapy in patients with an ischemic stroke.

METHODOLOGY:

  • The analysis, part of the Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, included 6100 patients, median age 65 years and 35.8% women, with a mild ischemic stroke, defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤ 5, or a high-risk transient ischemic attack of presumed atherosclerotic origin, from 222 sites in China.
  • Researchers randomly assigned patients within 72 hours of symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2-90) plus aspirin (100-300 mg on day 1 and 100 mg daily on days 2-21) or clopidogrel placebo plus aspirin (100-300 mg on day 1 and 100 mg daily for days 2-90) in a 2 × 2 factorial design that also compared immediate vs delayed statin therapy.
  • The primary efficacy outcome was any new stroke (ischemic or hemorrhagic) within 90 days.
  • Secondary efficacy outcomes included a composite of cardiovascular events (stroke, myocardial infarction, or death from cardiovascular causes) within 90 days.
  • The primary safety outcome was moderate to severe bleeding as defined according to criteria from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial.

TAKEAWAY:

  • A new stroke within 90 days occurred in 7.3% in the clopidogrel-aspirin group and 9.2% in the aspirin group (hazard ratio [HR], 0.79; 95% CI, 0.66-0.94; P = .008).
  • A composite cardiovascular event occurred in 7.5% in the clopidogrel-aspirin group and 9.3% in the aspirin group (HR, 0.80; 95% CI, 0.67-0.96).
  • Moderate to severe bleeding occurred in 0.9% in the clopidogrel-aspirin group and in 0.4% in the aspirin group (HR, 2.08; 95% CI, 1.07-4.04; P = .03), and risk for any bleeding was 3.1% in the clopidogrel-aspirin group and 2.1% in the aspirin group (HR, 1.50; 95% CI, 1.09-2.06).
  • Adverse events occurred in 21.3% in both groups, and serious adverse events occurred in 3.5% in the combination group and 2.9% in the aspirin group.

IN PRACTICE:

“The results of our trial potentially broaden the time window for the initiation of treatment, although there was more bleeding with the dual regimen than with the monotherapy,” the authors wrote.

In an accompanying editorial, Anthony S. Kim, MD, Weill Institute for Neurosciences, University of California, San Francisco, said he welcomes evidence to support expanding the time window for dual antiplatelet therapy, adding: “Perhaps new, more targeted antithrombotic agents on the horizon may hold promise for delivering an even more favorable balance of benefits and risks among patients with stroke.”

SOURCE:

The study was conducted by Ying Gao, MD, Department of Neurology, Beijing Tiantan Hospital, Beijing, China, and colleagues. It was published online on December 28, 2023 in The New England Journal of Medicine. Results from the INSPIRES trial were also reported at the European Stroke Organisation Conference in May.

LIMITATIONS:

The study excluded important patient populations such as those with a stroke of presumed cardioembolic origin and with moderate or severe stroke (NIHSS score > 5) and those who had undergone thrombolysis or thrombectomy. More than 98% of enrolled patients were Han Chinese who had a relatively high rate of intracranial artery stenosis, which may have contributed to the benefit from dual antiplatelet therapy. The results may not be generalized to White and Black patients with a stroke.

TAVR Now Used in Almost 50% of Younger Severe Aortic Stenosis Patients

Posted by

0


Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR) despite guideline recommendations to the contrary, a study in a national US population shows.

The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.

Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published today as a Research Letter in the Journal of the American College of Cardiology (JACC).

“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.

They analyzed changes in rates of TAVR and SAVR in a US sample stratified by age: younger than 65 years, 65 to 80, and older than 80 years.

These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability and the potential for subsequent TAVR procedures over time.”

Three Age Groups

In a study published in June in JACC, this group examined changes in uptake of TAVR vs SAVR in 4161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, told theheart.org | Medscape Cardiology in an interview.

The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dauerman, from the University of Vermont Health Network, Burlington.

The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.

The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.

From the Vizient clinical database, including more than 250 US academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from October 1, 2015, to December 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:

  • Age < 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
  • Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
  • Age > 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.

“All ages have grown in the last 7 years in TAVR,” Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”

Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.

Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dauerman noted.

European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.

There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.

Strategy Depends on More Than Age

The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, told theheart.org | Medscape Cardiology in an email.

“Age is only one of multiple patient characteristics that enter into consideration of TAVR vs SAVR,” said Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.

“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”

TAVR Now Used in Almost 50% of Younger Severe Aortic Stenosis Patients

Posted by

0


Among patients with severe isolated aortic stenosis younger than 65, the rate of transcatheter aortic valve replacement (TAVR) now almost matches that of surgical aortic valve replacement (SAVR) despite guideline recommendations to the contrary, a study in a national US population shows.

The 2020 American Heart Association/American College of Cardiology (AHA/ACC) valve guideline recommends SAVR for patients younger than 65 with severe aortic stenosis, the researchers note, but their study showed “near equal utilization between TAVR and SAVR in these younger patients by 2021,” at 48% and 52% respectively.

Toishi Sharma, MD, and colleagues presented these findings in an oral poster session at Transcatheter Cardiovascular Therapeutics 2022, and the study was simultaneously published today as a Research Letter in the Journal of the American College of Cardiology (JACC).

“To our knowledge, the current findings represent the first national temporal trends study stratifying [aortic stenosis] therapies according to guideline-recommended age groups: our observations demonstrate the dramatic growth of TAVR in all age groups, including young patients,” the researchers conclude.

They analyzed changes in rates of TAVR and SAVR in a US sample stratified by age: younger than 65 years, 65 to 80, and older than 80 years.

These findings have implications for lifetime management of younger patients who undergo TAVR, they write, “including issues related to lifetime coronary access, valve durability and the potential for subsequent TAVR procedures over time.”

Three Age Groups

In a study published in June in JACC, this group examined changes in uptake of TAVR vs SAVR in 4161 patients with aortic stenosis in Vermont, New Hampshire, and Maine, senior author Harold L. Dauerman, MD, told theheart.org | Medscape Cardiology in an interview.

The greatest rate of rise of TAVR was in the group younger than 65, but that study ended in 2019, said Dauerman, from the University of Vermont Health Network, Burlington.

The 2020 guideline stratifies TAVR and SAVR recommendations such that “less than 65 should primarily be a surgical approach and greater than 80 primarily a TAVR approach, while 65 to 80 is a gray zone, and shared decision-making becomes important,” he noted.

The group hypothesized that recent trials and technology have led to a national increase in TAVR in people younger than 65.

From the Vizient clinical database, including more than 250 US academic centers that perform both TAVR and SAVR, the researchers identified 142,953 patients who underwent TAVR or SAVR for isolated aortic stenosis from October 1, 2015, to December 31, 2021. From 2015 to 2021, the valve replacement rates in the three age groups changed as follows:

  • Age < 65: TAVR rose from 17% to 48%; SAVR fell from 83% to 52%.
  • Age 65-80: TAVR rose from 46% to 87%; SAVR fell from 54% to 12%.
  • Age > 80: TAVR rose from 83% to 99%; SAVR fell from 16% to 1%.

“All ages have grown in the last 7 years in TAVR,” Dauerman summarized. “The one that’s surprising, and in contradiction to the guideline, is the growth of TAVR in young patients less than 65.”

Among patients younger than 65, prior bypass surgery and congestive heart failure predicted the use of TAVR instead of surgery, whereas bicuspid aortic valve disease was the biggest predictor of surgery instead of TAVR.

Most studies on TAVR valve durability are limited to patients in the randomized trials who were primarily in their mid-70s to mid-80s, some of whom died before a 10-year follow-up, Dauerman noted.

European guidelines recommend surgery for patients younger than 70, and it would be interesting to see if clinicians there follow this recommendation or if TAVR is now the preferred approach, he added.

There is a need for further, longer study of TAVR in younger patients, he said, to determine whether there are long-term clinical issues of concern.

Strategy Depends on More Than Age

The “findings are not too surprising,” John Carroll, MD, who was not involved in this research, told theheart.org | Medscape Cardiology in an email.

“Age is only one of multiple patient characteristics that enter into consideration of TAVR vs SAVR,” said Carroll, from Anschutz Medical Campus, University of Colorado, Aurora.

“As the article reports,” he noted, “those less than 65 having TAVR are more likely to have comorbid conditions that likely made the risk of SAVR higher.”

Cardiovascular Assessment up to One Year After COVID-19 Vaccine–Associated Myocarditis

Posted by

0


Myocarditis has been recognized as a complication of COVID-19 mRNA vaccinations, particularly in adolescent and young adult male patients.[1] Cardiovascular sequelae after an acute episode of myocarditis, regardless of pathogenesis, remain as issues of concern. Although the reported short-term clinical trajectory after COVID-19 vaccine–associated myocarditis appears reassuring, with resolution of cardiac symptoms and normalization of left ventricular ejection fraction (LVEF) in most of the adolescent patients,[2] the long-term cardiovascular outcomes remain unclear.

We evaluated the cardiovascular outcomes at up to 1 year in adolescent patients diagnosed with COVID-19 vaccine–associated myocarditis. Their electrocardiographic, echocardiographic, and cardiac magnetic resonance (CMR) findings at diagnosis were reviewed. At latest follow-up, clinical assessment, ECG, echocardiogram (Vivid E9, GE Medical System, Horten, Norway), and CMR (Siemens Magnetom Aera 1.5 T MRI system, Germany) were performed. The study was approved by the Institutional Review Board and the parents of subjects gave informed consent. Data that support our findings are available from the corresponding authors on reasonable request.

Forty patients (33 male) 15.1±1.6 (range, 12.7–17.9) years of age and followed up for 10.0±1.3 (range, 5.6–12.3) months, representing all cases identified in Hong Kong during the period of study, were included. Twenty-nine (73%) patients were asymptomatic, whereas 7 (18%) reported noncardiac chest pain, 3 (8%) reported palpitations, and 1 (3%) reported fatigue during follow-up, with none having cardiac arrhythmias, angina, or heart failure. The ECG results were abnormal, with ST-segment or T-wave abnormalities in 31 (78%) patients at presentation and normalized in all at latest follow-up.

Echocardiographic assessment at presentation showed normal LVEF in all patients, mild increased echogenicity of the pericardium or left ventricular (LV) lateral wall in 6 (15%), and minimal (<2 mm) pericardial effusion in 2 (5%). At latest follow-up, 38 (95%) patients had normal LVEF, 2 (5%) had borderline LVEF of 51.1% and 53.6%, and all had normal right ventricular (RV) fractional area change. Analyses of RV and LV 4-chamber longitudinal strain were feasible, when ≥5 segments in each plane could be analyzed, in 36 patients and LV global longitudinal and circumferential strain in 35. The LV 4-chamber longitudinal, global longitudinal, and circumferential systolic strain was impaired (Z score <–2) in 8 (22%), 7 (20%), and 4 (11%) patients, respectively. The RV longitudinal systolic strain and early- and late-diastolic strain rates were impaired in 2 (6%), 3 (8%), and 10 (28%) patients, respectively. Mean Z scores of diastolic functional indices of both ventricles were significantly lower than zero (all P<0.002; Figure A). No patients had coronary abnormalities.

(Enlarge Image)

Figure.

Echocardiographic indices and cardiac magnetic resonance late gadolinium enhancement in adolescents at up to 1-year after COVID-19 vaccine–associated myocarditis.
A, Boxplots showing the distribution of Z scores, which indicate the number of standard deviations in relation to the mean, of echocardiographic parameters (*significantly different from zero after Bonferroni adjustment for multiple comparisons). The plots illustrate the median (horizontal line), the interquartile range (IQR; box) differences in Z score between the study population and a healthy reference population, and outliers (circles) that are less than first quartile minus 1.5*IQR or greater than third quartile plus 1.5*IQR. B, Cardiac magnetic resonance images showing persistence of late gadolinium enhancement, which was assessed qualitatively using the single-shot short axis, single-shot 4-chamber stack, segmented short-axis stack, and 3-dimensional inversion recovery sequence, in the basal inferolateral segment (arrows). C, Distribution of cardiac magnetic resonance late gadolinium enhancement based on the 17-segment model. LV indicates left ventricular; and RV, right ventricular.

Thirty-nine patients had CMR at presentation, 26 of whom had abnormal findings. These included features of myocarditis in 22 (56%), abnormal T1 values in 21 (54%), abnormal T2 values in 24 (62%), late gadolinium enhancement (LGE) in 19 (49%), and reduced LVEF in 7 (18%). The CMR-derived LVEF at initial assessment correlated with LV 4-chamber longitudinal (r=0.36, P=0.04), global longitudinal (r=0.41, P=0.02), and circumferential (r=0.38, P=0.03) absolute systolic strain at follow-up echocardiography. Follow-up CMR performed in 26 patients with initial abnormal CMR findings revealed mild residual LGE in 15 (58%; Figure B), borderline LVEF in 2 (8%), and normal findings in 11 (42%) patients. None of these patients had abnormal T1 (pregadolinium 1013±28 ms and postgadolinium 473±43 ms) or T2 (48±2 ms) values or features of myocarditis. For the patient without initial assessment, follow-up CMR showed mild LGE with normal LVEF. Distribution of LGE in the 16 patients shows predilection of involvement of lateral segments (Figure C). The presence of previous LGE correlated with LGE on follow-up (ϕ-coefficient=0.71, P<0.001). Patients with (n=16) and those without (n=11) LGE on follow-up CMR had similar demographic and echocardiographic parameters (all P>0.05).

To our knowledge, this is the longest follow-up study to date with comprehensive cardiac evaluation and imaging of adolescent patients diagnosed with COVID-19 vaccine–associated myocarditis. Global systolic ventricular function appears to be preserved. However, impairment of LV and RV myocardial deformation and persistence of LGE in a significant subset of patients with up to 1 year of follow-up was observed. Growing evidence suggests worse prognosis in the presence of altered myocardial deformation and LGE in patients with myocarditis.[3] A short-term study reported abnormal CMR-derived LV longitudinal strain and LGE in 70% to 75% of adolescent patients with COVID-19 vaccine–associated myocarditis followed up for 3 to 8 months.[4] Similar CMR findings were found in young adults studied at 3 to 6 months after the initial diagnosis.[5] The implications of impaired systolic and diastolic myocardial deformation and LGE in our patient subset remain unclear. Nonetheless, given that impaired myocardial deformation and LGE are indicators of subclinical myocardial dysfunction and fibrosis, there exists a potential long-term effect on exercise capacity and cardiac functional reserve during stress.

Limitations of our study include a relatively small patient cohort, the lack of a trajectory that depicts changes in myocardial deformation over time, and performance of CMR only in patients with initial abnormal CMR findings. Further long-term studies to define the clinical and functional implications of these subclinical abnormalities in a larger cohort are undoubtedly warranted.

Posted by

0


Newborn Recipient of Partial Heart Transplant Doing Well

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told theheart.org | Medscape Cardiology.

photo of Joseph Turek, MD
Joseph W. Turek, MD

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

photo of Dr Joseph W. Turek, with the patient.
Joseph W. Turek, MD, with the patient.

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Turek told theheart.org | Medscape Cardiology, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”