Frequency of Cardiac Valvulopathies in Patients With Marfan Syndrome: A Systematic Review and Meta-Analysis.

Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural valvular abnormalities as cardiovascular involvement has been identified as the most life-threatening aspect of the syndrome. This was a systematic review with a meta-analysis of studies indexed in Medline from the inception of the database to November 7, 2022. Using the random-effects model, separate Forest and Galbraith plots were generated for each valvular abnormality assessed. Heterogeneity was assessed using the I2 statistics whilst funnel plots and Egger's test were used to assess for publication bias. From a total of 35 studies, a random-effects meta-analysis approximated the pooled summary estimates for the prevalence of cardiac valve abnormalities as mitral valve prolapse 65% (95% CI: 57%-73%); mitral valve regurgitation 40% (95% CI: 29%-51%); aortic valve regurgitation 40% (95% CI: 28%-53%); tricuspid valve prolapse 35% (95% CI: 15%-55%); and tricuspid valve regurgitation 43% (95% CI: 8%-78%). Only one study reported on the involvement of the pulmonary valve (pulmonary valve prolapse was estimated at 5.3% (95% CI: 1.9%-11.1%) in a cohort of 114 patients with MFS). We believe this study provides a description of the structural valvular disease spectrum and may help inform providers and patients in understanding the clinical history of MFS in the current treatment era with its increased life expectancy.

Transcatheter aortic valve implantation with and without mitral stenosis - A national readmission database study.

INTRODUCTION: Mitral valve stenosis (MS) can be concomitantly present in patients undergoing Transcatheter Aortic Valve Implantation (TAVI). Some studies have reported up to one-fifth of patients who underwent TAVI also have MS. The relationship between mitral stenosis and TAVI has led to concerns regarding increased adverse cardiac outcomes during and after the procedure. METHODS: The Nationwide Readmission Database (NRD 2016-2019) was utilized to identify TAVI patients with MS with ICD-10-CM codes. The primary outcome was a 30-day readmission rate. Secondary outcomes included predictors of all-cause readmissions, length of stay, and total hospitalization cost. We assessed readmission frequency with a national sample weighed at 30 days following the index TAVI procedure. Unadjusted and adjusted odds ratios were analyzed for in-hospital outcomes using univariate and multivariate logistic regression for study cohorts. RESULTS: A total of 217,147 patients underwent TAVI procedures during the queried time period of the study. Of these patients, 2140 (0.98 %) had MS. The overall 30-day all-cause readmission rate for the study cohort was 12.4 %. TAVI patients with MS had higher rates of 30-day readmissions (15.8 % vs 12.3 %, aOR 1.22, CI: 1.03-1.45, P < 0.01). Additionally, TAVI patients with MS had longer lengths of hospital stay during index admissions (5.7 vs. 4.3 days), along with higher total hospitalization costs ($55,157 vs. $50,239). In contrast, in-hospital mortality during index TAVI admission did not differ significantly between the two groups, although there was a trend toward higher mortality in the MS group (2.1 % vs. 1.5 %). Among the TAVI MS cohort, patients admitted on weekends (aOR: 1.11, 95 % CI: 1.02-1.22, P = 0.01), admitted to non-metropolitan hospitals (aOR: 1.29, 95 % CI: 1.11-1.66, P = 0.04) and presence of co-morbidities such as atrial fibrillation (AF)/flutter (aOR: 1.24, 95 % CI: 1.16-1.32, P < 0.01), chronic obstructive pulmonary disease (COPD) (aOR: 1.16, 95 % CI: 1.11-1.22, P < 0.01), prior stroke (aOR: 1.09, 95 % CI: 1.03-1.14, P < 0.01), chronic kidney disease (CKD) ≥3 (aOR: 1.16, 95 % CI: 1.11-1.22, P < 0.01), end-stage renal disease (ESRD) (aOR: 1.75, 95 % CI: 1.61-1.90, P < 0.01), and anemia (aOR: 1.23, 95 % CI: 1.18-1.28, P < 0.01) were associated with increased odds of readmission. CONCLUSION: Concomitant MS in patients undergoing TAVI is associated with higher readmission rates and total hospital costs. This can contribute significantly to healthcare-related burdens. Further studies are required to evaluate in-hospital outcomes and predictors of readmission in patients undergoing TAVI with the presence of concomitant MS.

Non-calcified plaque in asymptomatic patients with zero coronary artery calcium score: A systematic review and meta-analysis.

BACKGROUND: There is growing interest in understanding the coronary atherosclerotic burden in asymptomatic patients with zero coronary artery calcium score (CACS). In this population, we aimed to investigate the prevalence and severity of non-calcified coronary plaques (NCP) as detected by coronary CT angiography (CCTA), and to analyze the associated clinical predictors. METHODS: This was a systematic review with meta-analysis of studies indexed in PubMed/Medline and Web of Science from inception of the database to March 31st, 2023. Using the random-effects model, separate Forest and Galbraith plots were generated for each effect size assessed. Heterogeneity was assessed using the I2 statistics whilst Funnel plots and Egger's test were used to assess for publication bias. RESULTS: From a total of 14 studies comprising 37808 patients, we approximated the pooled summary estimates for the overall prevalence of NCP to be 10% (95%CI: 6%-13%). Similarly, the pooled prevalence of obstructive NCP was estimated at 1.1% (95%CI: 0.7%-1.5%) from a total of 10 studies involving 21531 patients. Hypertension [OR: 1.46 (95%CI:1.31-1.62)] and diabetes mellitus [OR: 1.69 (95%CI: 1.41-1.97)] were significantly associated with developing any NCP, with male gender being the strongest predictor [OR: 3.22 (95%CI: 2.17-4.27)]. CONCLUSION: There is a low burden of NCP among asymptomatic subjects with zero CACS. In a subset of this population who have clinical predictors of NCP, the addition of CCTA has a potential to provide a better insight about occult coronary atherosclerosis, however, a risk-benefit approach must be factored in prior to CCTA use given the low prevalence of NCP.

Non-Calcified Coronary Artery Plaque on Coronary Computed Tomography Angiogram: Prevalence and Significance.

OBJECTIVE: We aimed to assess the prevalence of non-calcified plaque (NCP) on computed tomography angiography (CCTA) in symptomatic and asymptomatic individuals. In addition, we seek to compare plaque assessment on CCTA with intravascular ultrasound-virtual histology (IVUS-VH) and to assess the prognostic value of non-calcified plaques (NCPs). BACKGROUND: The CCTA can characterize coronary plaques and help quantify burden. Furthermore, it can provide additional prognostic information which can enable further risk stratification of patients. METHODS: We performed a broad comprehensive review of the current literature pertaining to CCTA and primarily isolated NCP in symptomatic and asymptomatic patients. In addition, our review included studies correlating plaque on CT with IVUS-VH. CONCLUSIONS: NCP is the initial precursor of calcified plaque and serves as a prominent marker of early coronary atherosclerosis. By detecting NCP during early stages, several measures can be implemented which can alter the evolutionary course of the underlying disease. This can potentially lead to a lower incidence of cardiovascular events.

A systematic review and meta-analysis of the prevalence, incidence, and predictors of atrial fibrillation in cardiac sarcoidosis.

BACKGROUND: The occurrence of atrial arrhythmias, in particular, atrial fibrillation (AF) in patients with cardiac sarcoidosis (CS) are of growing interest in the field of infiltrative cardiomyopathies. Via a systematic review with meta-analysis, we sought to synthesize data on the prevalence, incidence, and predictors of atrial arrhythmias as well as outcomes in patients with CS. METHODS: PubMed/Medline, Web of Science, and Scopus were systematically queried from inception until April 26th, 2023. Using the random-effects model, separate plots were generated for each effect size assessed. RESULTS: From a total of 8 studies comprising 978 patients with CS, the pooled summary estimates for the prevalence of AF was 23% (95% CI: 13%-34%). Paroxysmal AF was the most common subtype of AF (83%; 95% CI: 77%-90%), followed by persistent AF (17%; 95% CI: 10%-23%). In 9 studies involving 545 patients with CS, the pooled incidence of AF was estimated at 5%, 13.1%, and 8.9% at <2 years, 2-4 years, and > 4 years of follow-up respectively, with an overall cumulative incidence of 10.6% (95% CI: 4.9%-17.8%) over a 6-year follow-up period. Increased left atrial size and atrial 18F-fluorodeoxyglucose uptake were identified as strong independent predictors for the development of atrial arrhythmias on qualitative synthesis. CONCLUSION: The burden of AF and related arrhythmias in CS patients is considerable. This necessitates close follow-up and predictive risk-stratification tools to guide the initiation of appropriate strategies, including therapeutic interventions for prevention of AF-related embolic phenomenon, especially in those with known clinical predictors.

Predictors of non-calcified plaque presence and future adverse cardiovascular events in symptomatic rural Appalachian patients with a zero coronary artery calcium score.

BACKGROUND: Coronary artery calcium (CAC) scoring is a proven predictor for future adverse cardiovascular events (CVE) in asymptomatic individuals. Data is emerging regarding the usefulness of non-calcified plaque (NCP) assessment on cardiac computed tomography (CCT) angiography in symptomatic patients with a zero CAC score for further risk assessment. METHODS: A retrospective review from January 2019 to January 2022 of 696 symptomatic patients with no known CAD and a zero CAC score identified 181 patients with NCP and 515 patients without NCP by a visual assessment on CCT angiography. The primary endpoint was to identify predictors for NCP presence and adverse CVEs (death, myocardial infarction, or cerebrovascular accident) within two years. RESULTS: Based on logistic regression, age (OR 1.039, 95% CI [1.020-1.058], p â€‹< â€‹0.001), diabetes mellitus (OR 2.192, 95% CI [1.307-3.676], p â€‹< â€‹0.003), tobacco use (OR 1.748, 95% CI [1.157-2.643], p â€‹< â€‹0.008), low-density lipoprotein cholesterol level (OR 1.009, 95% CI [1.003-1.015], p â€‹< â€‹0.002), and hypertension (OR 1.613, 95% CI [1.024-2.540], p â€‹< â€‹0.039) were found to be predictors of NCP presence. NCP patients had a higher pretest probability for CAD using the Morise risk score (p â€‹< â€‹0.001∗), with NCP detection increasing as pretest probability increased from low to high (OR 55.79, 95% CI [24.26-128.26], p â€‹< â€‹0.001∗). 457 patients (66%) reached a full two-year period after CCT angiography completion, with NCP patients noted to have shorter follow-up times and higher rates of elective coronary angiography, intervention, and CVEs. The presence of NCP (aOR 2.178, 95% CI [1.025-4.627], p â€‹< â€‹0.043) was identified as an independent predictor for future adverse CVEs when adjusted for diabetes mellitus, age, and hypertension. CONCLUSION: NCP was identified at high rates (26%) in our symptomatic Appalachian population with no known CAD and a zero CAC score. NCP was identified as an independent predictor of future adverse CVEs within two years.

Persistent Left Superior Vena Cava Draining Directly Into the Left Atrium With Occluded Coronary Sinus.

Combined persistent left superior vena cava entering the left atrium with a congenitally atretic coronary sinus is a rare imaging finding. In the absence of a significant right-to-left shunt, it is generally asymptomatic and can be an incidental discovery. Assessing the anatomy of the cardiac vasculature is crucial before transcutaneous cardiac procedures. (Level of Difficulty: Intermediate.).

Quantitative single photon emission computed tomography derived standardized uptake values on 99mTc-PYP scan in patients with suspected ATTR cardiac amyloidosis.

Technetium-99 pyrophosphate scintigraphy (99mTc-PYP) provides qualitative and semiquantitative diagnosis of ATTR cardiac amyloidosis (ATTR-CA) using the Perugini scoring system and heart/contralateral heart ratio (H/CL) on planar imaging. Standardized uptake values (SUV) with quantitative single photon emission computed tomography (xSPECT/CT) can offer superior diagnostic accuracy and quantification through precise myocardial contouring that enhances assessment of ATTR-CA burden. We examined the correlation of xSPECT/CT SUVs with Perugini score and H/CL ratio. We also assessed SUV correlation with cardiac magnetic resonance (CMR), echocardiographic, and baseline clinical characteristics. Retrospective review of 78 patients with suspected ATTR-CA that underwent 99mTc-PYP scintigraphy with xSPECT/CT. Patients were grouped off Perugini score (Grade 0-1 and Grade 2-3), H/CL ratio (≥ 1.5 and < 1.5). Two cohorts were also created: myocardium SUVmax > 1.88 and ≤ 1.88 at 1-hour based off an AUC curve with 1.88 showing the greatest sensitivity and specificity. Cardiac SUV retention index was calculated as [SUVmax myocardium/SUVmax vertebrae] × SUVmax paraspinal muscle. Primary outcome was myocardium SUVmax at 1-hour correlation with Perugini grades, H/CL ratio, CMR, and echocardiographic data. Higher Perugini Grades corresponded with higher myocardium SUVmax values, especially when comparing Perugini Grade 3 to Grade 2 and 1 (3.03 ± 2.1 vs 0.59 ± 0.97 and 0.09 ± 0.2, P < 0.001). Additionally, patients with H/CL ≥ 1.5 had significantly higher myocardium SUVmax compared to patients with H/CL ≤ 1.5 (2.92 ± 2.18 vs 0.35 ± 0.60, P < 0.01). Myocardium SUVmax at 1-hour strongly correlated with ECV (r = 0.91, P = 0.001), pre-contrast T1 map values (r = 0.66, P = 0.037), and left ventricle mass index (r = 0.80, P = 0.002) on CMR. SUVs derived from 99mTc-PYP scintigraphy with xSPECT/CT provides a discriminatory and quantitative method to diagnose and assess ATTR-CA burden. These findings strongly correlate with CMR.

Evaluating Gender-based Differences in Clinical Outcomes for Patients Undergoing Left Atrial Appendage Occlusion: A Single Centre Experience.

There is emerging recent data that has shown women to be more prone to in-hospital major adverse events after trans catheter left atrial appendage occlusion. Institutional LAAO registry at West Virginia University (WVU) was reviewed from January 2016 to October 2021 to identify 271 women and 293 men who underwent successful LAAO device implantation. Patients were evaluated for gender-based differences in baseline characteristics, CHA2DS2-VASc Score, HAS-BLED score, procedural data, in-hospital, and follow-up outcomes. Compared to men, women had lower baseline comorbidities including coronary artery disease (135 (49.6%) vs 172 (58.7%), P = 0.03), myocardial infarction (MI) (56 (20.5%) vs 85 (29%), P = 0.02) and coronary artery bypass surgery (10 (3.6%) vs 27 (9.2%), P = 0.008). Women were noted to have a higher CHA2DS2-VASc Score (5.3 ± 1.4 vs 4.4 ± 1.4, P < 0.001), and left ventricular ejection fraction (57.9 ± 7.7 vs 52.7 ± 12.4, P < 0.001). Women were noted to have a significantly higher rate of in-hospital composite adverse events (74 (27.2%) vs 58 (19.8%), P = 0.03); bleeding events (38 (10.2%) vs 19 (6.4%), P = 0.003) and associated blood transfusion (6 vs 0, P = 0.001) compared with men. No statistically significant differences were noted between both genders regarding the follow-up outcome. Our single center study shows women to have higher in-hospital composite adverse events as well as higher bleeding events during the index hospital admission.

A case report of congenital absence of the pericardium that was diagnosed by cardiac computed tomography angiogram (CCTA).

This case report describes a 40-year-old male who presented to the emergency department (ED) with chest pain. Initial diagnostic workup was concerning for a congenital cardiac anomaly, further imaging revealed complete congenital absence of the pericardium (CAP) which is a rare condition. Multimodality cardiac imaging including cardiac computed tomography angiogram (CCTA) was used to confirm the diagnosis of CAP. We briefly discuss various clinical presentations of CAP along with potential complications and other anomalies that could be associated with pericardial agenesis.

Case Report of an Elderly Woman Who Presented with Hypothermia and an Electrocardiographic Finding of a J Wave.

BACKGROUND This report is of a 92-year-old woman who presented with hypothermia and an electrocardiogram (ECG) finding of a J wave, or Osborn wave. On ECG, the J wave had an elevation of the J point at the junction of the QRS complex and ST segment, which usually appears at a body temperature below 32°C. CASE REPORT A 92-year-old woman presented to our hospital with an altered mental status. On evaluation, the vital signs were significant for low temperature (34.7°C), and she looked dehydrated. An ECG was performed as a part of the initial assessment and displayed normal sinus rhythm with an elevation of the J point (Osborn wave). Empiric antibiotic coverage was initiated for possible sepsis, in addition to supportive measures including hydration and passive external warming. By the next day, the patient's hypothermia was resolved, with improvement in her mental status, and a repeated ECG showed disappearance of the Osborn waves after appropriate warming. CONCLUSIONS This case highlights the importance of recognizing the J wave, or Osborn wave, and distinguishing it from ST-segment elevation seen in ischemic cardiac injury. Identification of the J wave is neither a specific finding nor predictive of patient outcome from hypothermia; however, an ECG should be performed in all patients with hypothermia as it serves a pivotal role in preventing progression to ventricular arrhythmia by prompt intervention and management.

Longitudinal Follow-Up of Asymptomatic COVID-19 Myocarditis with Cardiac Magnetic Resonance Imaging.

BACKGROUND Varying degrees of cardiovascular involvement have been noted with COVID-19, with myocarditis being one of the feared complications. We present the case of a healthy, young individual with persistent myocardial involvement on cardiac magnetic resonance (CMR) imaging at 10 months' follow-up. CASE REPORT A 23-year-old man with no prior medical conditions presented to our outpatient cardiology clinic with a chief concern of left-sided exertional chest discomfort of 1-week duration, lasting 30-60 min before resolving. The patient was previously active and ran 2 miles per day, 6 days a week without any issues. Three months prior to presentation, the patient had a mild case of COVID-19 managed conservatively on an outpatient basis. On evaluation, the vital signs, physical examination, and laboratory work-up were unremarkable. Electrocardiography (EKG) displayed normal sinus rhythm with incomplete right bundle branch block. Transthoracic echocardiography (TTE) was normal. CMR was performed and indicated myopericarditis in several sub-epicardial and pericardial segments, with a quantitative scar burden of 18.6% on late gadolinium enhancement (LGE) images using the mean+5 SD method. A repeat CMR 7 months later demonstrated persistent sub-epicardial fibrosis with improvement in the LGE burden to 5.1% and resolution of pericarditis. CONCLUSIONS Myopericarditis with persistent myocardial scarring can be detected using CMR in healthy individuals with mild COVID-19 symptoms. The exact prevalence and potential clinical implications of this entity is unclear and warrants further longitudinal research.

Cardiac Computed Tomography Angiography for Device-Related Thrombus Assessment After WATCHMAN FLX™ Occluder Device Implantation: A Single-Center Retrospective Observational Study.

BACKGROUND/PURPOSE: Device-related thrombosis (DRT) is one of the greatest challenges of transcatheter left atrial appendage device occlusion. Due to the invasive nature of transesophageal echocardiography (TEE), cardiac computed tomography angiography (CCTA) is being increasingly utilized in several centers for assessing adequate left atrial appendage closure and monitoring for DRT. There is a paucity of data regarding the standardized definition of DRT on CCTA for the WATCHMAN FLX™ device. METHODS/MATERIALS: A retrospective review was conducted on 43 patients receiving WATCHMAN FLX™ device implantation with CCTA performed at the first follow-up at our institution. A comparative review of DRT predictors was performed on 10 patients who had both CCTA and TEE at the time of follow-up. RESULTS: Hypoattenuated thickening (HAT) was a common finding on CCTA and was noted to be present in 95.35% of the patients. The combination of a large device size, peridevice gap >4 mm, and HAT located on the device gutter and 1 shoulder were characteristics present on CCTA observed in 2 patients with confirmed DRT on TEE. CONCLUSION: CCTA is a noninvasive imaging modality for DRT monitoring, with guidelines still in development. We report potential predictors of DRT on CCTA. Additional studies are needed to further determine standardized parameters for DRT detection on CCTA and the significance of HAT with multimodality correlation.

CT assessment of the left atrial appendage post-transcatheter occlusion - A systematic review and meta analysis.

BACKGROUND: Transesophageal echocardiography (TEE) is the standard imaging modality used to assess the left atrial appendage (LAA) after transcatheter device occlusion. Cardiac computed tomography angiography (CCTA) offers an alternative non-invasive modality in these patients. We aimed to conduct a comparison of the two modalities. METHODS: We performed a comprehensive systematic review of the current literature pertaining to CCTA to establish its usefulness during follow-up for patients undergoing LAA device closure. Studies that reported the prevalence of inadequate LAA closure on both CCTA and TEE were further evaluated in a meta-analysis. 19 studies were used in the systematic review, and six studies were used in the meta-analysis. RESULTS: The use of CCTA was associated with a higher likelihood of detecting LAA patency than the use of TEE (OR, 2.79, 95% CI 1.34-5.80, p â€‹= â€‹0.006, I2 â€‹= â€‹70.4%). There was no significant difference in the prevalence of peridevice gap ≥5 â€‹mm (OR, 3.04, 95% CI 0.70-13.17, p â€‹= â€‹0.13, I2 â€‹= â€‹0%) between the two modalities. Studies that reported LAA assessment in early and delayed phase techniques detected a 25%-50% higher prevalence of LAA patency on the delayed imaging. CONCLUSION: CCTA can be used as an alternative to TEE for LAA assessment post occlusion. Standardized CCTA acquisition and interpretation protocols should be developed for clinical practice.

Noninvasive Detection of Early Metabolic Left Ventricular Remodeling in Systemic Hypertension.

OBJECTIVES: Hypertension (HTN) is a common cause of left ventricular hypertrophy (LVH). Sustained pressure overload induces a permanent myocardial switch from fatty-acid to glucose metabolism. In this study, we tested the hypothesis that metabolic remodeling, characterized by increased myocardial glucose uptake, precedes structural and functional remodeling in HTN-induced LVH. METHODS: We recruited 31 patients: 11 with HTN only, 9 with HTN and LVH and 11 normotensive controls without LVH. Transthoracic echocardiography was performed to assess the function, mass, wall thickness and diastolic function of the left ventricle. Positron emission tomography imaging was performed, and the rate of myocardial 2-deoxy-2-[18F]fluoro-D-glucose uptake, Ki, was determined using a 3-compartment kinetic model. RESULTS: The mean Ki values were significantly higher in HTN patients than in those with HTN and LVH (p < 0.001) and in controls (p = 0.003). The unexpected decrease in Ki with LVH may be secondary to a decreased Ki with diastolic dysfunction (DD), 0.039 ± 0.032 versus 0.072 ± 0.013 (p = 0.004). There was also a significant stepwise decrease in Ki with increasing DD grade (p = 0.04). CONCLUSION: Glucose metabolic remodeling is detectable in hypertensive patients before the development of LVH. Furthermore, lower glucose uptake rates are observed in patients with DD. The mechanism for this last finding requires further investigation.

Large serpiginous thrombus straddling the patent foramen ovale and traversing through mitral and tricuspid valves into both ventricles: a therapeutic dilemma of impending paradoxical embolism and recurrent pulmonary embolism.

A 51-year-old male with history of resected renal cell carcinoma and prior pulmonary embolism presented with tachypnea, tachycardia and progressive dyspnea on exertion. Chest computed tomography revealed bilateral acute pulmonary embolism. Transthoracic echocardiogram showed severe pulmonary hypertension with severe cor-pulmonale and presence of a large worm-like thrombus extending across the foramen ovale, entering both ventricles through the mitral and tricuspid valves. The risks of anti-coagulation, pharmacologic thrombolysis, and surgical thrombectomy, in a hemodynamically stable patient, posed a significant therapeutic dilemma. Ultimately, a collective decision was made to start anticoagulation, without incident. At 1 month follow up, complete resolution of the intracardiac thrombus, pulmonary hypertension, and cor-pulmonale were observed with full clinical recovery of the patient.

Effect of microvascular obstruction and intramyocardial hemorrhage by CMR on LV remodeling and outcomes after myocardial infarction: a systematic review and meta-analysis.

The goal of this systematic analysis is to provide a comprehensive review of the current cardiac magnetic resonance data on microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). Data related to the association of MVO and IMH in patients with acute myocardial infarction (MI) with left ventricular (LV) function, volumes, adverse LV remodeling, and major adverse cardiac events (MACE) were critically analyzed. MVO is associated with a lower ejection fraction, increased ventricular volumes and infarct size, and a greater risk of MACE. Late MVO is shown to be a stronger prognostic marker for MACE and cardiac death, recurrent MI, congestive heart failure/heart failure hospitalization, and follow-up LV end-systolic volumes than early MVO. IMH is associated with LV remodeling and MACE on pooled analysis, but because of limited data and heterogeneity in study methodology, the effects of IMH on remodeling require further investigation.