Publications by authors named "Christopher Kramer"

Artificial intelligence-enhanced electrocardiography (AI-ECG) can identify hypertrophic cardiomyopathy (HCM) on 12-lead ECGs and offers a novel way to monitor treatment response. Although the surgical or percutaneous reduction of the interventricular septum (SRT) represented initial HCM therapies, mavacamten offers an oral alternative. We aimed to assess the use of AI-ECG as a strategy to evaluate biologic responses to SRT and mavacamten.

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Article Synopsis
  • Obesity is linked to heart failure with preserved ejection fraction (HFpEF), characterized by changes in heart structure and increased epicardial adipose tissue (EAT), which can lead to negative health outcomes.
  • The SUMMIT trial's CMR substudy aimed to assess how tirzepatide influenced cardiac structure and function in patients with obesity-related HFpEF, focusing on its potential to lower left ventricular (LV) mass and EAT.
  • Results showed that tirzepatide treatment significantly reduced LV mass by 11 g and paracardiac adipose tissue by 45 ml compared to placebo, with changes in LV mass correlated to body weight and other cardiac measures.
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Background: Patients with heart failure, a preserved ejection fraction (HFpEF), and obesity have significant disability and suffer frequent exacerbations of heart failure. We hypothesized that tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, would improve a comprehensive suite of clinical endpoints, including measures of health status, functional capacity, quality of life, exercise tolerance, patient well-being, and medication burden in these patients.

Methods: 731 patients in class II-IV heart failure, ejection fraction ≥50%, and body mass index ≥30 kg/m were randomized(double-blind) to tirzepatide(titrated up to 15mg subcutaneously weekly)(n=364) or placebo(n=367), added to background therapy for a median of 104 weeks (Q1=66, Q3=126 weeks).

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Background: Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes.

Methods: In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks.

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Patients with obesity-related heart failure with preserved ejection fraction (HFpEF) display circulatory volume expansion and pressure overload contributing to cardiovascular-kidney end-organ damage. In the SUMMIT trial, patients with HFpEF and obesity were randomized to the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide (n = 364, 200 women) or placebo (n = 367, 193 women). As reported separately, tirzepatide decreased cardiovascular death or worsening heart failure.

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Background: Hypertrophic cardiomyopathy (HCM) is a heterogeneous condition that can lead to atrial fibrillation, heart failure, and sudden cardiac death in many individuals but mild clinical impact in others. The mechanisms underlying this phenotypic heterogeneity are not well defined. The aim of this study was to use plasma proteomic profiling to help illuminate biomarkers that reflect or inform the heterogeneity observed in HCM.

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Article Synopsis
  • Guidelines suggest using ECG-triggered mid-diastolic CCTA after heart rate optimization for better image quality, but switching to prospective end-systolic acquisition may reduce motion artifacts and the need for beta-blockers.
  • An institutional change in January 2023 was made to adopt an algorithmic approach using prospective end-systolic acquisition without routine beta-blocker use, and image quality was assessed over three phases using a specific scoring model.
  • Results showed that after the process change, the median appointment time significantly decreased, indicating improved efficiency in performing CCTAs while maintaining image quality.
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Background: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) hypertrophy, LV outflow tract obstruction, and left atrial dilation, which can be associated with progressive heart failure, atrial fibrillation, and stroke. Aficamten is a next-in-class cardiac myosin inhibitor that reduces outflow tract obstruction by modulating cardiac contractility, with the potential to reverse pathological remodeling and, in turn, reduce cardiovascular events.

Objectives: This study sought to investigate the effect of aficamten on cardiac remodeling compared with placebo using cardiovascular magnetic resonance (CMR) and its association with key clinical endpoints in the SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) CMR substudy.

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Background: Aficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study.

Objectives: The authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM.

Methods: Serial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF).

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Women are disproportionately affected by symptoms of angina with nonobstructive coronary arteries (ANOCA) which is associated with significant mortality and economic impact. Although distinct endotypes of ANOCA have been defined, it is underdiagnosed and is often incompletely characterized when identified. Patients are often unresponsive to traditional therapeutic options, which are typically antianginal, and the current ability to guide treatment modification by specific pathways is limited.

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Introduction: Heart failure with preserved ejection fraction (HFpEF) is a complex disease process influenced by metabolic disorders, systemic inflammation, myocardial fibrosis, and microvascular dysfunction. The goal of our study is to identify potential relationships between plasma biomarkers and cardiac magnetic resonance (CMR) imaging markers in patients with HFpEF.

Methods: Nineteen subjects with HFpEF and 15 age-matched healthy controls were enrolled and underwent multiparametric CMR and plasma biomarker analysis using the Olink® Cardiometabolic Panel (Olink Proteomics, Uppsala, Sweden).

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Article Synopsis
  • This phase 2 trial assessed the safety and effectiveness of a medication called aficamten in patients suffering from nonobstructive hypertrophic cardiomyopathy (nHCM).
  • 41 patients participated, and after 10 weeks of treatment, over half showed improvement in heart failure symptoms, with many reaching a better functional class.
  • While some patients experienced a slight decrease in heart function (LVEF), the overall results indicated that aficamten is generally safe and effective in improving symptoms and relevant heart health markers.
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Article Synopsis
  • Artificial intelligence-enhanced electrocardiography (AI-ECG) can detect hypertrophic cardiomyopathy (HCM) and monitor treatment responses through ECGs, presenting a modern alternative to surgical options like septal reduction therapy (SRT) and oral treatments like mavacamten.
  • A study involving patients from multiple health systems showed no significant change in AI-ECG HCM scores after SRT, indicating that this surgical method may not effectively improve HCM scores.
  • In contrast, patients on mavacamten therapy showed a significant decrease in their AI-ECG scores over a median follow-up period, suggesting that AI-ECG could be useful for regularly tracking improvements in HCM
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Susac Syndrome was first described as an inflammatory microangiopathy of the brain and retina. Since then, multiple articles have been published in attempts to improve the understanding of this rare disease. Clinically Susac Syndrome is known to present with triad of encephalopathy, sensorineural hearing loss and branch of retinal artery occlusion (BRAO), along with characteristic "snowball" or "spoke" appearing white matter lesions of the corpus callosum.

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Acute onset of a cold, painful leg, also known as acute limb ischemia, describes the sudden loss of perfusion to the lower extremity and carries significant risk of morbidity and mortality. Acute limb ischemia requires rapid identification and the management of suspected vascular compromise and is inherently driven by clinical considerations. The objectives of initial imaging include confirmation of diagnosis, identifying the location and extent of vascular occlusion, and preprocedural/presurgical planning.

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Perfusion Imaging for the Heart.

Magn Reson Imaging Clin N Am

February 2024

The use of myocardial perfusion imaging during a stress cardiac magnetic resonance (CMR) examination for the evaluation of coronary artery disease is now recommended by both US and European guidelines. Several studies have demonstrated high diagnostic accuracy for the detection of hemodynamically significant coronary artery disease. Stress perfusion CMR has been shown to be a noninvasive and cost-effective alternative to guide coronary revascularization.

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Article Synopsis
  • The study aimed to develop a deep learning model (DESIRE) for rapid image reconstruction and segmentation to measure left ventricular ejection fraction (LVEF) using high-resolution cardiac imaging methods, such as 2D balanced steady-state free precession and gradient echo imaging.
  • A new 3D U-Net network was used for image reconstruction, while a 2D U-Net was used for segmenting the left ventricle, with low-rank plus sparse (L+S) methods as benchmarks for comparison.
  • Results showed that DESIRE provided comparable image quality to L+S and matched manual segmentation performance in LVEF quantification, with significantly faster reconstruction times (32 seconds vs. 3 minutes for L+
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Background: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD).

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Tertiary hospitals with expertise in hypertrophic cardiomyopathy (HCM) are assuming a greater role in confirming and correcting HCM diagnoses at referring centers. The objectives were to establish the frequency of alternate diagnoses from referring centers and identify predictors of accuracy of an HCM diagnosis from the referring centers. Imaging findings from echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging (CMR) in 210 patients referred to an HCM Center of Excellence between September 2020 and October 2022 were reviewed.

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Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for non-invasive myocardial tissue characterisation. However, accurate segmentation of the left ventricular (LV) myocardium remains a challenge due to limited training data and lack of quality control. This study addresses these issues by leveraging generative adversarial networks (GAN)-generated virtual native enhancement (VNE) images to expand the training set and incorporating an automated quality control-driven (QCD) framework to improve segmentation reliability.

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A multimodality imaging evaluation in hypertrophic cardiomyopathy is often used for risk stratification. Recent developments in imaging have allowed for better diagnosis, prognosis, and decision-making for a variety of therapies from medical to interventional. Echocardiography and magnetic resonance have been integral in evaluating subtype, left ventricular function, tissue characterization, left atrial measurements, valvular function, and presence of left ventricular aneurysm and outflow tract obstruction.

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Objective: To develop two spiral-based bSSFP pulse sequences combined with L + S reconstruction for accelerated ungated, free-breathing dynamic cardiac imaging at 1.5 T.

Materials And Methods: Tiny golden angle rotated spiral-out and spiral-in/out bSSFP sequences combined with view-sharing (VS), compressed sensing (CS), and low-rank plus sparse (L + S) reconstruction were evaluated and compared via simulation and in vivo dynamic cardiac imaging studies.

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