Impact of Heart Failure Etiology on Waitlist Mortality in Heart Transplant Candidates Supported With Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has gained traction as a bridge to heart transplantation (HT) but remains associated with increased waitlist mortality. This study explores whether this risk is modified by underlying heart failure (HF) etiology. METHODS: Using the Organ Procurement and Transplantation Network registry, we conducted a retrospective review of first-time adult HT candidates from 2018 through 2022. Patients were categorized as "ECMO", if ECMO was utilized during the waitlisting period, or "No ECMO" otherwise. Patients were then stratified according to the following HF etiology: ischemic cardiomyopathy (CMP), dilated nonischemic CMP, restrictive CMP, hypertrophic CMP, and congenital heart disease (CHD). After baseline comparisons, waitlist mortality was characterized for ECMO and HF etiology using the Fine-Gray regression. RESULTS: A total of 16 143 patients were identified of whom 7.0% (n = 1063) were bridged with ECMO. Compared to No ECMO patients, ECMO patients had shorter waitlist durations (46.3 vs. 185.0 days, p < 0.01) and were more likely to undergo transplantation (75.3% vs. 70.3%, p < 0.01). Outcomes analysis revealed that ECMO was associated with increased mortality risk (subdistribution hazard ratio [SHR]: 3.42, p < 0.01), a risk that persisted in all subgroups and was notably high in CHD (SHR: 4.83, p < 0.01) and hypertrophic CMP (SHR: 9.78, p < 0.01). HF etiology comparison within ECMO patients revealed increased mortality risk with CHD (SHR: 3.22, p < 0.01). Within No ECMO patients, hypertrophic CMP patients had lower mortality risk (SHR: 0.64, p = 0.03). CONCLUSIONS: The increased waitlist mortality risk with ECMO persisted after stratification by HF etiology. These findings can help decision-making surrounding candidacy for cannulation and prognostic evaluation.

HF Etiology and cardiac contractility modulation therapy.

OBJECTIVES: Our study aimed to assess the safety and efficacy of cardiac contractility modulation (CCM) therapy in patients with heart failure with reduced ejection fraction (HFrEF) depending on HF etiology. METHODS: We enrolled 166 patients with optimal medical therapy-resistant HFrEF (median age 59 years, 83.7% males, median NYHA class - 2, median left ventricular ejection fraction (LVEF) - 29.0%) who underwent CCM therapy device implantation from 2013 to 2019 in four medical centers in Russia. The HF etiology was determined based on invasive coronary angiography or cardiac MRI data. Transthoracic echocardiography (TTE), 6-minute walking test (6MWT), and NTproBNP-tests were performed at a baseline and 12 months after the implantation. RESULTS: The ischemic etiology of HF was revealed in 100 patients (61.5%) (ICM group); the non-ischemic group (NICM) evolved 66 patients (38.5%). Patients in the ICM group were significantly older (61[57-69] vs. 55 [42.8-61], p < 0.001), more frequently had hypertension (79% vs. 42.4%, p < 0.001) and chronic kidney disease (43% vs. 22.7%, p = 0.012). Patients in the NICM group had significantly more often atrial fibrillation (AF) (58% vs. 74%, p = 0.048), larger end-diastolic volume (EDV) (249 [208-309] vs. 220 [192-271], p = 0.019) and end-systolic volume (ESV) (183 [147-230] vs. 154 [128-199], p = 0.003). There were no significant differences in mortality between ICM and NICM groups (14.4 vs. 10.8%, p = 0.51). In 12 months, there was a significant increase in LVEF in the NICM group (+ 2.0 [2-6] vs. +7.7 [2-12], p < 0.001), while the improvement in the 6MWT (+ 75 [22-108] vs. +80 [10-160], p = 0.851) and NYHA class did not reach the level of significance. The subanalysis between patients with improved NYHA class and those without improvement revealed that patients without improvement more frequently had AF (56% vs. 89%; p < 0.01), chronic obstructive lung disease (18% vs. 35% p = 0.047), higher blood pressure (110 [105-120] vs. 120[110-129]; p = 0.032). CONCLUSION: In this multicenter retrospective study, patients with non-ischemic HFrEF showed a significantly higher improvement in LVEF and LV reverse remodeling following CCM therapy device implantation. There was no significant association between HF etiology and survival in drug-resistant HFrEF patients following CCM therapy.

Impact of Elevated Fibroblast Growth Factor 23 (FGF23) on the Cardiovascular System: A Comprehensive Systematic Literature Review.

Fibroblast growth factors (FGF) are a type of cell signaling proteins that are mostly produced by macrophages. They are essential for a variety of biological activities involved in normal development. Fibroblast growth factor 23 (FGF23) is the newest and youngest member of the FGF endocrine subfamily, along with fibroblast growth factor 19 (FGF19) and fibroblast growth factor 21 (FGF21). In this study, we conduct a systematic review of all known literature to identify the risk of elevated FGF23 in the cardiovascular system. The analysis includes the risk of cardiovascular disease for both primary and secondary causes of elevated FGF23, such as chronic renal insufficiency. This systematic literature review adhered to the Preferred Reporting Items and Meta-Analysis (PRISMA) standards. A total of 4,793 records were identified across different databases. After that, 273 records were retrieved and reviewed. After carefully examining the titles and summaries of each report, 249 additional entries were eliminated. About 24 studies from the remaining records were chosen by primary and secondary authors for screening, and they performed a quality assessment using common quality check tools. Finally, this review included 11 studies. Following a thorough analysis, we came to the conclusion that FGF23 can be regarded as a novel biomarker and should be included in the group of heart biomarkers that have already been identified, such as B-type natriuretic peptide (BNP), for the early identification of a variety of highly prevalent cardiovascular disorders.

Reshaping the Ventricle From Within: MIRTH (Myocardial Intramural Remodeling by Transvenous Tether) Ventriculoplasty in Swine.

MIRTH (Myocardial Intramural Remodeling by Transvenous Tether) is a transcatheter ventricular remodeling procedure. A transvenous tension element is placed within the walls of the beating left ventricle and shortened to narrow chamber dimensions. MIRTH uses 2 new techniques: controlled intramyocardial guidewire navigation and EDEN (Electrocardiographic Radial Depth Navigation). MIRTH caused a sustained reduction in chamber dimensions in healthy swine. Midventricular implants approximated papillary muscles. MIRTH shortening improved myocardial contractility in cardiomyopathy in a dose-dependent manner up to a threshold beyond which additional shortening reduced performance. MIRTH may help treat dilated cardiomyopathy. Clinical investigation is warranted.

Cause of Death in Heart Failure Based on Etiology: Long-Term Cohort Study of All-Cause and Cardiovascular Mortality.

We assessed differences in long-term all-cause and cardiovascular (CV) mortality in heart failure (HF) outpatients based on the etiology of HF. Consecutive patients admitted to the HF Clinic from August 2001 to September 2019 (N = 2587) were considered for inclusion. HF etiology was divided into ischemic heart disease (IHD), dilated cardiomyopathy (DCM), hypertensive heart disease, alcoholic cardiomyopathy, drug-induced cardiomyopathy (DICM), valvular heart disease, and hypertrophic cardiomyopathy. All-cause death and CV death were the primary end points. Among 2387 patients included in the analysis (mean age 66.5 ± 12.5 years, 71.3% men), 1317 deaths were recorded (731 from CV cause) over a maximum follow-up of 18 years (median 4.1 years, interquartile range (IQR) 2-7.8). Considering IHD as the reference, only DCM had a lower risk of all-cause death (adjusted hazard ratio (aHR) 0.68, 95% confidence interval (CI) 0.56-0.83, p < 0.001), and only DICM had a higher risk of all-cause death (aHR 1.47, 95% CI 1.02-2.11, p = 0.04). However, almost all etiologies had a significantly lower risk of CV death than IHD. Among the studied HF etiologies, DCM and DICM have the lowest and highest risk of all-cause death, respectively, whereas IHD has the highest adjusted risk of CV death.

Continuous-Flow Left Ventricular Assist Device Support in Patients with Ischemic Versus Nonischemic Cardiomyopathy.

To determine whether the cause of cardiomyopathy affects outcomes in patients who undergo continuous-flow left ventricular assist device support, we compared postimplant adverse events and survival between patients with ischemic and nonischemic cardiomyopathy. The inclusion criteria for the ischemic group were a history of myocardial infarction or revascularization (coronary artery bypass grafting or percutaneous coronary intervention), ≥75% stenosis of the left main or proximal left anterior descending coronary artery, or ≥75% stenosis of ≥2 epicardial vessels. From November 2003 through March 2016, 526 patients underwent device support: 256 (48.7%) in the ischemic group and 270 (51.3%) in the nonischemic group. The ischemic group was older (60.0 vs 50.0 yr), included more men than women (84.0% vs 72.6%), and had more comorbidities. More patients in the nonischemic group were able to have their devices explanted after left ventricular recovery (5.9% vs 2.0%; P=0.02). More patients in the ischemic group had gastrointestinal bleeding (31.2% vs 22.6%; P=0.03), particularly from arteriovenous malformations (20.7% vs 11.9%; P=0.006) and ulcers (16.4% vs 9.3%; P=0.01). Kaplan-Meier analysis revealed no difference in overall survival between groups (P=0.24). Older age, previous sternotomy, higher total bilirubin level, and concomitant procedures during device implantation independently predicted death (P ≤0.03), whereas cause of heart failure did not (P=0.08). Despite the similarity in overall survival between groups, ischemic cardiomyopathy was associated with more frequent gastrointestinal bleeding. This information may help guide the care of patients with ischemic cardiomyopathy who receive continuous-flow left ventricular assist device support.

Unusual Cause of Heart Failure in a Patient with Marfan Syndrome: A Late Complication of Bioprosthetic Valved Graft Replacement.

A high-velocity gradient across the left ventricular outflow tract is most often caused by aortic valve stenosis. We describe the unusual case of a high-velocity gradient caused by a kinked ascending aortic graft in a 69-year-old man who had Marfan syndrome. The patient had a history of ascending aortic aneurysm and had previously undergone replacement of the aortic root and ascending aorta with use of a bioprosthetic valved graft. The kinking was caused by dilation of the native aortic arch. The patient underwent successful hemi-arch replacement and repair of the kinked graft. Late complications and reoperation after proximal aortic surgery in patients with Marfan syndrome are rare, and a high-velocity left ventricular outflow tract gradient caused by the kinking of the aorta is unusual.

Left Ventricular Noncompaction Detected by Cardiac Magnetic Resonance Screening: A Reexamination of Diagnostic Criteria.

In a previous cross-sectional screening study of 5,169 middle and high school students (mean age, 13.1 ± 1.78 yr) in which we estimated the prevalence of high-risk cardiovascular conditions associated with sudden cardiac death, we incidentally detected by cardiac magnetic resonance (CMR) 959 cases (18.6%) of left ventricular noncompaction (LVNC) that met the Petersen diagnostic criterion (noncompaction:compaction ratio >2.3). Short-axis CMR images were available for 511 of these cases (the Short-Axis Study Set). To determine how many of those cases were truly abnormal, we analyzed the short-axis images in terms of LV structural and functional variables and applied 3 published diagnostic criteria besides the Petersen criterion to our findings. The estimated prevalences were 17.5% based on trabeculated LV mass (Jacquier criterion), 7.4% based on trabeculated LV volume (Choi criterion), and 1.3% based on trabeculated LV mass and distribution (Grothoff criterion). Absent longitudinal clinical outcomes data or accepted diagnostic standards, our analysis of the screening data from the Short-Axis Study Set did not definitively differentiate normal from pathologic cases. However, it does suggest that many of the cases might be normal anatomic variants. It also suggests that cases marked by pathologically excessive LV trabeculation, even if asymptomatic, might involve unsustainable physiologic disadvantages that increase the risk of LV dysfunction, pathologic remodeling, arrhythmias, or mural thrombi. These disadvantages may escape detection, particularly in children developing from prepubescence through adolescence. Longitudinal follow-up of suspected LVNC cases to ascertain their natural history and clinical outcome is warranted.

Left Ventricular Noncompaction Cardiomyopathy Presenting with Heart Failure in a 35-Year-Old Man.

Isolated ventricular noncompaction, a rare genetic cardiomyopathy, is thought to be caused by the arrest of normal myocardial morphogenesis. It is characterized by prominent, excessive trabeculation in a ventricular wall segment and deep intertrabecular recesses perfused from the ventricular cavity. The condition can present with heart failure, systematic embolic events, and ventricular arrhythmias. Two-dimensional echocardiography is the typical diagnostic method. We report a case of heart failure in a 35-year-old man who presented with palpitations. Two-dimensional echocardiograms revealed left ventricular noncompaction, which markedly improved after standard heart failure therapy.

Right Ventricular Enlargement within Months of Arteriovenous Fistula Creation in 2 Hemodialysis Patients.

Surgically created arteriovenous fistulae (AVF) for hemodialysis can contribute to hemodynamic changes. We describe the cases of 2 male patients in whom new right ventricular enlargement developed after an AVF was created for hemodialysis. Patient 1 sustained high-output heart failure solely attributable to the AVF. After AVF banding and subsequent ligation, his heart failure and right ventricular enlargement resolved. In Patient 2, the AVF contributed to new-onset right ventricular enlargement, heart failure, and ascites. His severe pulmonary hypertension was caused by diastolic heart failure, diabetes mellitus, and obstructive sleep apnea. His right ventricular enlargement and heart failure symptoms did not improve after AVF ligation. We think that our report is the first to specifically correlate the echocardiographic finding of right ventricular enlargement with AVF sequelae. Clinicians who treat end-stage renal disease patients should be aware of this potential sequela of AVF creation, particularly in the upper arm. We recommend obtaining preoperative echocardiograms in all patients who will undergo upper-arm AVF creation, so that comparisons can be made postoperatively. Alternative consideration should be given to creating the AVF in the radial artery, because of less shunting and therefore less potential for right-sided heart failure and pulmonary hypertension. A multidisciplinary approach is optimal when selecting patients for AVF banding or ligation.

Cardiomyopathy induced by pulmonary sequestration in a 50-year-old man.

A 50-year-old black man presented at the emergency department with midsternal, nonradiating chest pressure and chronic dyspnea on exertion. Four years before the current admission, he had been diagnosed with nonischemic cardiomyopathy at another facility. After our complete evaluation, we suspected that his symptoms arose from left-to-left shunting in association with pulmonary sequestration, a congenital malformation. Our preliminary diagnosis of secondary dilated cardiomyopathy was confirmed by normalization of the patient's ventricular size and function after lobectomy. To our knowledge, this patient is the oldest on record to present with cardiomyopathy consequent to pulmonary sequestration. His case is highly unusual because of his age and the rapid resolution of his symptoms after lobectomy. We believe that pulmonary sequestration should be included in the differential diagnosis of dilated cardiomyopathy.

Regression of a large congenital hepatic arteriovenous malformation.

Congenital hepatic arteriovenous malformations are rarely seen in association with persistent neonatal pulmonary hypertension. We report the case of a full-term female newborn who presented with heart failure and respiratory distress soon after birth. Echocardiographic investigation revealed severe persistent pulmonary hypertension and patent ductus arteriosus. Here we report spontaneous regression in size of both the feeder vessel and the vascular bed of the congenital hepatic arteriovenous malformation. We postulate that our conservative use of oral heart failure therapy, in the form of diuretic agents and captopril, decreased the congestion and diameter of the affected vessels.

The prevention of cardiovascular disease in cancer survivors.

The number of cancer survivors in the United States has exceeded 12 million and is increasing. After secondary malignancies, cardiovascular disease is the leading cause of late morbidity and death among cancer survivors. The cardiovascular needs of cancer survivors have not been described. We describe the clinical characteristics of 53 patients seen during the first year of our Cardiovascular Prevention in Cancer Survivors clinic. The mean age of the patients was 40.1 ± 13.7 years. The mean survival since cancer diagnosis was 13.9 years. A history of chemotherapy-induced cardiomyopathy was present in 21%, and 5.7% had known atherosclerotic disease. One fourth had hypertension; 32.1%, dyslipidemia; and 13%, diabetes mellitus. Three quarters had received anthracycline chemotherapy, while half had received radiation. Half had an abnormal echocardiogram (55%), and 11 of 18 had an abnormal carotid ultrasonogram. The mean Framingham risk score for patients older than 30 years (n=37) was 8.4, yielding a 10-year risk of cardiovascular disease of 7.6%. The mean vascular age was 54.3 years, and the mean chronological age was 46.3 years. The mean follow-up duration was 566 ± 213 days. There were significant improvements in serum triglycerides and high-density lipoprotein levels, as well as trends toward improved blood pressure control. Cardiovascular risk factors are prevalent in cancer survivors. There is an immediate need for the widespread availability of cardiovascular preventive services to reduce the late adverse effects of chemotherapy and radiation. Early intervention might help to improve the cardiovascular risk profile.

Acute eosinophilic myocarditis mimicking myocardial infarction.

Eosinophilic myocarditis is characterized by progressive myocardial damage that results in heart failure and death. Herein, we present the case of a 54-year-old man who presented with symptoms of acute myocardial infarction. Normal coronary angiographic results and the presence of elevated levels of peripheral-blood eosinophilia prompted an endomyocardial biopsy that revealed acute eosinophilic myocarditis. The early initiation of steroid therapy resulted in the patient's substantial clinical improvement and survival. Early diagnosis of eosinophilic myocarditis and its treatment with steroid agents in some patients can lead to a favorable outcome. We discuss the challenge of diagnosing and identifying the characteristics of this variant of necrotizing eosinophilic myocarditis before the condition proves fatal.

Syncope from dynamic left ventricular outflow tract obstruction simulating hypertrophic cardiomyopathy in a patient with primary AL-type amyloid heart disease.

Dynamic left ventricular outflow tract (LVOT) obstruction is seen classically in hypertrophic cardiomyopathy. Cardiac amyloidosis can present with asymmetric hypertrophy that resembles hypertrophic cardiomyopathy, and, in some cases, with dynamic LVOT obstruction. The occurrence of syncope in such patients is not uncommon. The syncope is usually thought to be related to mechanisms other than LVOT obstruction, such as arrhythmias, conduction disturbances, orthostatic hypotension, or vasovagal effects associated with neuropathy.Herein, we report the case of a patient who had immunocyte-derived (primary AL-type) cardiac amyloidosis with the echocardiographic appearance of hypertrophic cardiomyopathy and evidence of LVOT obstruction that caused syncope. We were able to provoke and identify dynamic LVOT obstruction that produced presyncopal symptoms similar to those that typically occur in such patients spontaneously. Dynamic LVOT obstruction as a cause of syncope should be considered in patients who have cardiac amyloidosis and echocardiographic evidence of hypertrophic cardiomyopathy.