Iron deficiency and all-cause mortality after myocardial infarction.

BACKGROUND: Data on the clinical significance of iron deficiency (ID) in patients with myocardial infarction (MI) are conflicting. This may be related to the use of various ID criteria. We aimed to compare the association of different ID criteria with all-cause mortality after MI. METHODS: Consecutive patients hospitalized for their first MI at a large tertiary heart center were included. We evaluated the association of different iron metabolism parameters measured on the first day after hospital admission with all-cause mortality. RESULTS: From the 1,156 patients included (aged 64±12 years, 25 % women), 194 (16.8 %) patients died during the median follow-up of 3.4 years. After multivariate adjustment, iron level ≤13 µmol/L (HR 1.67, 95 % CI 1.19-2.34) and the combination of iron level ≤12.8 µmol/L and soluble transferrin receptor (sTfR) ≥3 mg/L (HR 2.56, 95 % CI 1.64-3.99) termed as PragueID criteria were associated with increased mortality risk and had additional predictive value to the GRACE score. Compared to the model including iron level, the addition of sTfR improved risk stratification (net reclassification improvement 0.61, 95 % CI 0.52-0.69) by reclassifying patients into a higher-risk group. No association between ferritin level and mortality was found. 51 % of patients had low iron levels, and 58 % fulfilled the PragueID criteria. CONCLUSION: Iron deficiency is common among patients with the first MI. The PragueID criteria based on iron and soluble transferrin receptor levels provide the best prediction of mortality and should be evaluated in future interventional studies for the identification of patients potentially benefiting from intravenous iron therapy.

Efficacy and Safety of Stereotactic Radiotherapy in Patients With Recurrent Ventricular Tachycardias: The Czech Experience.

BACKGROUND: Stereotactic arrhythmia radiotherapy (STAR) has been proposed recently in patients with refractory ventricular tachycardia (VT). OBJECTIVES: The purpose of this study was to describe the efficacy and safety of STAR in the Czech Republic. METHODS: VT patients were recruited in 2 expert centers after at least 1 previously failed catheter ablation (CA). A precise strategy of target volume determination and CA was used in 17 patients treated from December 2018 until June 2022 (EFFICACY cohort). This group, together with an earlier series of 19 patients with less-defined treatment strategies, composed the SAFETY cohort (n = 36). A dose of 25 Gy was delivered. RESULTS: In the EFFICACY cohort, the burden of implantable cardioverter-defibrillator therapies decreased, and this drop reached significance for direct current shocks (1.9 ± 3.2 vs 0.1 ± 0.2 per month; P = 0.03). Eight patients (47%) underwent repeated CA for recurrences of VT during 13.7 ± 11.6 months. In the SAFETY cohort (32 procedures, follow-up >6 months), 8 patients (25%) presented with a progression of mitral valve regurgitation, and 3 (9%) required intervention (median follow-up of 33.5 months). Two cases of esophagitis (6%) were seen with 1 death caused by the esophago-pericardial fistula (3%). A total of 18 patients (50%) died during the median follow-up of 26.9 months. CONCLUSIONS: Although STAR may not be very effective in preventing VT recurrences after failed CA in an expert center, it can still modify the arrhythmogenic substrate, and when used with additional CA, reduce the number of implantable cardioverter-defibrillator shocks. Potentially serious sides effects require close follow-up.

One-year mortality and causes of death after stereotactic radiation therapy for refractory ventricular arrhythmias: A systematic review and pooled analysis.

Patients treated with cardiac stereotactic body radiation therapy (radioablation) for refractory ventricular arrhythmias are patients with advanced structural heart disease and significant comorbidities. However, data regarding 1-year mortality after the procedure are scarce. This systematic review and pooled analysis aimed at determining 1-year mortality after cardiac radioablation for refractory ventricular arrhythmias and investigating leading causes of death in this population. MEDLINE/EMBASE databases were searched up to January 2023 for studies including patients undergoing cardiac radioablation for the treatment of refractory ventricular arrhythmias. Quality of included trials was assessed using the NIH Tool for Case Series Studies (PROSPERO CRD42022379713). A total of 1,151 references were retrieved and evaluated for relevance. Data were extracted from 16 studies, with a total of 157 patients undergoing cardiac radioablation for refractory ventricular arrhythmias. Pooled 1-year mortality was 32 % (95 %CI: 23-41), with almost half of the deaths occurring within three months after treatment. Among the 157 patients, 46 died within the year following cardiac radioablation. Worsening heart failure appeared to be the leading cause of death (52 %), although non-cardiac mortality remained substantial (41 %) in this population. Age≥70yo was associated with a significantly higher 12-month all-cause mortality (p<0.022). Neither target volume size nor radiotherapy device appeared to be associated with 1-year mortality (p = 0.465 and p = 0.199, respectively). About one-third of patients undergoing cardiac stereotactic body radiation therapy for refractory ventricular arrhythmias die within the first year after the procedure. Worsening heart failure appears to be the leading cause of death in this population.

Acute and Long-Term Scar Characterization of Venous Ethanol Ablation in the Left Ventricular Summit.

BACKGROUND: Venous ethanol ablation (VEA) can be effective for ventricular arrhythmias from the left ventricular summit (LVS); however, there are concerns about excessive ablation by VEA. OBJECTIVES: The purpose of this study was to delineate and quantify the location, extent, and evolution of ablated tissue after VEA as an intramural ablation technique in the LVS. METHODS: VEA was performed in 59 patients with LVS ventricular arrhythmias. Targeted intramural veins were selected by electrograms from a 2F octapolar catheter or by guide-wire unipolar signals. Median ethanol delivered was 4 mL (IQR: 4-7 mL). Ablated areas were estimated intraprocedurally as increased echogenicity on intracardiac echocardiography (ICE) and incorporated into 3-dimensional maps. In 44 patients, late gadolinium enhancement cardiac magnetic resonance (CMR) imaged VEA scar and its evolution. RESULTS: ICE-demonstrated increased intramural echogenicity (median volume of 2 mL; IQR: 1.7-4.3) at the targeted region of the 3-dimensional maps. Post-ethanol CMR showed intramural scar of 2.5 mL (IQR: 2.1-3.5 mL). Early (within 48 hours after VEA) CMR showed microvascular obstruction (MVO) in 30 of 31 patients. Follow-up CMR after a median of 51 (IQR: 41-170) days showed evolution of MVO to scar. ICE echogenicity and CMR scar volumes correlated with each other and with ethanol volume. Ventricular function and interventricular septum remained intact. CONCLUSIONS: VEA leads to intramural ablation that can be tracked intraprocedurally by ICE and creates regions of MVO that are chronically replaced by myocardial scar. VEA scar volume does not compromise septal integrity or ventricular function.

Role of genetics in the development of cardiac allograft vasculopathy.

BACKGROUND: The association between genetic polymorphisms and early cardiac allograft vasculopathy (CAV) development is relatively unexplored. Identification of genes involved in the CAV process may offer new insights into pathophysiology and lead to a wider range of therapeutic options. METHODS: This prospective study of 109 patients investigated 44 single nucleotide polymorphisms (SNPs) within the susceptibility loci potentially related to coronary artery disease, carotid artery intima-media thickness (cIMT), and in nitric oxide synthase gene. Genotyping was done by the Fluidigm SNP Type assays and Fluidigm 48.48 Dynamic Array IFC. The intima thickness progression (IT) was evaluated by coronary optical coherence tomography performed 1 month and 12 months after heart transplantation (HTx). RESULTS: During the first post-HTx year, the mean intima thickness (IT) increased by 24.0 ± 34.2 µm (p < 0.001) and lumen area decreased by ‒0.9 ± 1.8 mm2 (p < 0.001). The rs1570360 (A/G) SNP of the vascular endothelial growth factor A (VEGFA) gene showed the strongest association with intima thickness progression, even in the presence of the traditional CAV risk factors. SNPs previously related to carotid artery intima-media thickness rs11785239 (PRAG1), rs6584389 (PAX2), rs13225723 (LINC02577) and rs17477177 (CCDC71L), were among the five most significantly associated with IT progression but lost their significance once traditional CAV risk factors had been added. CONCLUSION: Results of this study suggest that genetic variability may play an important role in CAV development. The vascular endothelial growth factor A gene SNP rs1570360 showed the strongest association with intima thickness (IT) progression measured by OCT, even in the presence of the traditional CAV risk factors (Tab. 3, Fig. 3, Ref. 36). Text in PDF www.elis.sk Keywords: cardiac allograft vasculopathy, optical coherence tomography, vascular endothelial growth factor A, intimal thickening, genetic polymorphism.

Inflammation and fibrosis characterize different stages of myocardial remodeling in patients after stereotactic body radiotherapy of ventricular myocardium for recurrent ventricular tachycardia.

We performed a histological and immunohistochemical analysis of myocardia from 3 patients who underwent radiosurgery and died for various reasons 3 months to 9 months after radiotherapy. In Case 1 (death 3 months after radiotherapy) we observed a sharp transition between relatively intact and irradiated regions. In the myolytic foci, only scattered cardiomyocytes were left and the area was infiltrated by immune cells. Using immunohistochemistry we detected numerous inflammatory cells including CD68+/CD11c+ macrophages, CD4+ and CD8+ T-lymphocytes and some scattered CD20+ B-lymphocytes. Mast cells were diminished in contrast to viable myocardium. In Case 2 and Case 3 (death 6 and 9 months after radiotherapy, respectively) we found mostly fibrosis, infiltration by adipose tissue and foci of calcification. Inflammatory infiltrates were less pronounced. Our observations are in accordance with animal experimental studies and confirm a progress from myolysis to fibrosis. In addition, we demonstrate a role of pro-inflammatory macrophages in the earlier stages of myocardial remodeling after stereotactic radioablation for ventricular tachycardia.

Stereotactic Radiotherapy in the Management of Ventricular Tachycardias: More Questions than Answers?

Stereotactic body radiotherapy is a recent promising therapeutic alternative in cases of failed catheter ablation for recurrent ventricular tachycardias (VTs) in patients with structural heart disease. Initial clinical experience with a single radiation dose of 25 Gy shows reasonable efficacy in the reduction of VT recurrences with acceptable acute toxicity. Many unanswered questions remain, including unknown mechanism of action, variable time to effect, optimal method of substrate targeting, long-term safety, and definition of an optimal candidate for this treatment."

Metformin treatment is associated with improved outcome in patients with diabetes and advanced heart failure (HFrEF).

The role of metformin (MET) in the treatment of patients with advanced HFrEF and type 2 diabetes mellitus (DM) is not firmly established. We studied the impact of MET on metabolic profile, quality of life (QoL) and survival in these patients. A total of 847 stable patients with advanced HFrEF (57.4 ± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6 ± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Despite worse insulin sensitivity and more severe DM (higher BMI, HbA1c, worse insulin resistance), MET-treated patients exhibited more stable HF marked by lower BNP level (400 vs. 642 ng/l), better LV and RV function, lower mitral and tricuspid regurgitation severity, were using smaller doses of diuretics (all p < 0.05). Further, they had higher eGFR (69.23 vs. 63.34 ml/min/1.73 m2) and better QoL (MLHFQ: 36 vs. 48 points, p = 0.002). Compared to diabetics treated with other glucose-lowering agents, MET-treated patients had better event-free survival even after adjustment for BNP, BMI and eGFR (p = 0.035). Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p = 0.01). MET treatment in patients with advanced HFrEF and DM is associated with improved outcome by mechanisms beyond the improvement of blood glucose control.

Case Report: Repeated Stereotactic Radiotherapy of Recurrent Ventricular Tachycardia: Reasons, Feasibility, and Safety.

Stereotactic body radiotherapy (SBRT) has been reported as an attractive option for cases of failed catheter ablation of ventricular tachycardia (VT) in structural heart disease. However, even this strategy can fail for various reasons. For the first time, this case series describes three re-do cases of SBRT which were indicated for three different reasons. The purpose in the first case was the inaccuracy of the determination of the treatment volume by indirect comparison of the electroanatomical map and CT scan. A newly developed strategy of co-registration of both images allowed precise targeting of the substrate. In this case, the second treatment volume overlapped by 60% with the first one. The second reason for the re-do of SBRT was an unusual character of the substrate-large cardiac fibroma associated with different morphologies of VT from two locations around the tumor. The planned treatment volumes did not overlap. The third reason for repeated SBRT was the large intramural substrate in the setting of advanced heart failure. The first treatment volume targeted arrhythmias originating in the basal inferoseptal region, while the second SBRT was focused on adjacent basal septum without significant overlapping. Our observations suggested that SBRT for VT could be safely repeated in case of later arrhythmia recurrences (i.e., after at least 6 weeks). No acute toxicity was observed and in two cases, no side effects were observed during 32 and 22 months, respectively. To avoid re-do SBRT due to inaccurate targeting, the precise and reproducible strategy of substrate identification and co-registration with CT image should be used.

Adrenal pheochromocytoma as a rare cause of reversible left ventricular systolic dysfunction and malignant arrhythmias: a case series.

Background: Pheochromocytoma is a neuroendocrine tumour originating from the chromaffin cells of adrenal glands or sympathetic paraganglia. It produces most frequently norepinephrine, epinephrine, and dopamine. As a result of non-specific and variable clinical presentation, pheochromocytoma is difficult to diagnose. Case summary: A 37-year-old female without medical history and 57-year-old male patient with diabetes, arterial hypertension, and aortic valve replacement with a mechanical prosthesis were admitted to the hospital after successful cardiopulmonary resuscitation due to ventricular fibrillation. In both patients, coronary angiography demonstrated a normal finding, and echocardiography showed left ventricular (LV) contractile dysfunction with improvement in the subsequent examination. In the first patient, the diagnosis of stress-induced cardiomyopathy was considered as the most probable cause. She was later admitted to hospital due to acute pulmonary oedema with hypertensive crisis. Echocardiography documented reversible LV systolic dysfunction with improvement after 3 days. The course of hospitalization of the male was complicated by multi-organ dysfunction syndrome comprising renal failure, paralytic ileus, and pancreatic irritation, which normalized after 2 weeks. The diagnosis of pheochromocytoma was confirmed by laboratory tests and imaging methods. After pharmacological pre-treatment with doxazosin in both patients and bisoprolol in the female, successful adrenalectomies were performed with no relapse of tumour. Discussion: We describe an atypical clinical presentation of pheochromocytoma with initial cardiac arrest due to ventricular fibrillation and reversible LV systolic dysfunction. Our cases underline that clinical suspicion of pheochromocytoma as a potentially correctable cause should be raised in unexplained cases of severe heart failure, ventricular arrhythmias, and cardiac arrest.

Acute efficacy of contiguous versus temporally discontiguous point-by-point radiofrequency pulmonary vein isolation in patients with paroxysmal atrial fibrillation: a randomized study.

PURPOSE: Durable pulmonary vein (PV) isolation (PVI) determines the clinical success of catheter ablation for atrial fibrillation. In this randomized study, we investigated whether the temporally discontiguous deployment of ablation lesions adversely affected the acute efficacy of PVI. METHODS: Thirty-six consecutive patients with drug-refractory paroxysmal atrial fibrillation (aged 59 ± 11, 58% males) were randomized 1:1 to either discontiguous (D-PVI) or contiguous (C-PVI) encircling radiofrequency (RF) lesions around ipsilateral PVs. A contact force-sensing catheter was used targeting a final interlesion distance < 6 mm and the ablation index of 400-450 (anterior wall) and 300-350 (posterior wall). The study endpoint was defined as failure of first-pass PVI or acute PV reconnection during a waiting time (> 30 min) followed by adenosine challenge. RESULTS: The total RF time, number of RF lesions, and mean interlesion distance were comparable in both groups. Total endpoint rates were 1/36 (3%) in the D-PVI vs 4/36 (11%) in the C-PVI groups; P = 0.34 for superiority, P = 0.008 for non-inferiority. Adenosine-induced reconnection of right PVs was the only endpoint in the D-PVI group. In the C-PVI group, first-pass PVI failed in 2 right PVs and spontaneous reconnection occurred in 2 other circles (left and right PVs). CONCLUSION: Temporally discontiguous deployment of RF lesions is not associated with lower procedural PVI efficacy when strict criteria for interlesion distance and ablation index are applied. The development of local edema around each ablation site does not prevent effective RF lesion formation at adjacent positions. TRIAL REGISTRATION: clinicaltrials.gov (NCT03332862).

The prevalence of left and right bundle branch block morphology ventricular tachycardia amongst patients with arrhythmogenic cardiomyopathy and sustained ventricular tachycardia: insights from the European Survey on Arrhythmogenic Cardiomyopathy.

AIMS: In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. METHODS AND RESULTS: Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients' clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P < 0.001). Mutations in PKP2 predominated in the LBBB-VT (65.2%) and the LBBB + RBBB-VT (41.7%) groups while DSP mutations predominated in the RBBB-VT group (45.5%). By multivariable analysis, female sex was associated with LBBB + RBBB-VT (P = 0.011) while DSP mutations were associated with RBBB-VT (P < 0.001). After a median follow-up of 103 (51-185) months, death occurred in 106 (11.1%) patients with no intergroup difference (P = 0.176). CONCLUSION: RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

Temperature-Controlled Catheter Ablation for Paroxysmal Atrial Fibrillation: the QDOT-MICRO Workflow Sttudy.

BACKGROUND: A novel QDOT MICRO (Biosense Webster, Inc., Irvine, CA) catheter with optimized temperature control and microelectrodes was designed to incorporate real-time temperature sensing with contact force detection and microelectrodes to streamline ablation workflow. The QDOT-MICRO feasibility study evaluated the workflow, performance, and safety of temperature-controlled catheter ablation in patients with symptomatic paroxysmal atrial fibrillation with conventional ablation setting. METHODS: This was a non-randomized, single-arm, first-in-human study. The primary outcome was pulmonary vein isolation (PVI), confirmed by entrance block after adenosine and/or isoproterenol challenge. Safety outcomes included incidences of early-onset primary adverse events (AEs) and serious adverse device effects (SADEs). Device performance was evaluated via physician survey. RESULTS: All evaluated patients (n = 42) displayed 100% PVI. Two primary AEs (4.8%) were reported: 1 pericarditis and 1 vascular pseudoaneurysm. An additional SADE of localized infection was reported in 1 patient. No stroke, patient deaths, or other unanticipated AEs were reported. Average power delivered was 32.1±4.1 W, with a mean temperature of 40.8°C±1.6°C. Mean procedure (including 20-minute wait), fluoroscopy, and radiofrequency application times were 129.8, 6.7, and 34.0 minutes, respectively. On device performance, physicians reported overall satisfactory performance with the new catheter, with highest scores for satisfaction and usefulness of the temperature indicator. CONCLUSIONS: Initial clinical experience with the novel catheter showed 100% acute PVI success and acceptable safety and device performance in temperature-controlled ablation mode. There were no deaths, stroke, or unanticipated AEs. Fluoroscopy and procedural times were short and similar or better than reported for prior generation catheters.

Radiation-Induced Changes in Ventricular Myocardium After Stereotactic Body Radiotherapy for Recurrent Ventricular Tachycardia.

Stereotactic body radiotherapy (SBRT) has been suggested as a promising therapeutic alternative in cases of failed catheter ablation for recurrent ventricular tachycardias (VTs) in patients with structural heart disease. This case series is the first postmortem immunohistochemical analysis of morphologic changes in the myocardium early and late after SBRT. The present findings are in line with experimental observations on apoptosis followed by fibrosis. This may explain why the effect of SBRT on VT is not predominantly immediate. Together with observation of early recurrences after SBRT for VT, these data suggest that this strategy may have rather delayed antiarrhythmic effects.

Accuracy of electroanatomical mapping-guided cardiac radiotherapy for ventricular tachycardia: pitfalls and solutions.

AIMS: To analyse and optimize the interobserver agreement for gross target volume (GTV) delineation on cardiac computed tomography (CCT) based on electroanatomical mapping (EAM) data acquired to guide radiotherapy for ventricular tachycardia (VT). METHODS AND RESULTS: Electroanatomical mapping data were exported and merged with the segmented CCT using manual registration by two observers. A GTV was created by both observers for predefined left ventricular (LV) areas based on preselected endocardial EAM points indicating a two-dimensional (2D) surface area of interest. The influence of (interobserver) registration accuracy and availability of EAM data on the final GTV and 2D surface location within each LV area was evaluated. The median distance between the CCT and EAM after registration was 2.7 mm, 95th percentile 6.2 mm for observer #1 and 3.0 mm, 95th percentile 7.6 mm for observer #2 (P = 0.9). Created GTVs were significantly different (8 vs. 19 mL) with lowest GTV overlap (35%) for lateral wall target areas. Similarly, the highest shift between 2D surfaces was observed for the septal LV (6.4 mm). The optimal surface registration accuracy (2.6 mm) and interobserver agreement (Δ interobserver EAM surface registration 1.3 mm) was achieved if at least three cardiac chambers were mapped, including high-quality endocardial LV EAM. CONCLUSION: Detailed EAM of at least three chambers allows for accurate co-registration of EAM data with CCT and high interobserver agreement to guide radiotherapy of VT. However, the substrate location should be taken in consideration when creating a treatment volume margin.

Real-time measurement of ICD lead motion during stereotactic body radiotherapy of ventricular tachycardia.

BACKGROUND: Here we aimed to evaluate the respiratory and cardiac-induced motion of a ICD lead used as surrogate in the heart during stereotactic body radiotherapy (SBRT) of ventricular tachycardia (VT). Data provides insight regarding motion and motion variations during treatment. MATERIALS AND METHODS: We analyzed the log files of surrogate motion during SBRT of ventricular tachycardia performed in 20 patients. Evaluated parameters included the ICD lead motion amplitudes; intrafraction amplitude variability; correlation error between the ICD lead and external markers; and margin expansion in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions to cover 90% or 95% of all amplitudes. RESULTS: In the SI, LL, and AP directions, respectively, the mean motion amplitudes were 5.0 ± 2.6, 3.4. ± 1.9, and 3.1 ± 1.6 mm. The mean intrafraction amplitude variability was 2.6 ± 0.9, 1.9 ± 1.3, and 1.6 ± 0.8 mm in the SI, LL, and AP directions, respectively. The margins required to cover 95% of ICD lead motion amplitudes were 9.5, 6.7, and 5.5 mm in the SI, LL, and AP directions, respectively. The mean correlation error was 2.2 ± 0.9 mm. CONCLUSIONS: Data from online tracking indicated motion irregularities and correlation errors, necessitating an increased CTV-PTV margin of 3 mm. In 35% of cases, the motion variability exceeded 3 mm in one or more directions. We recommend verifying the correlation between CTV and surrogate individually for every patient, especially for targets with posterobasal localization where we observed the highest difference between the lead and CTV motion.