Single-center Study Research Articles

Improving the yield of genetic testing in dilated cardiomyopathy using late gadolinium enhancement

Abstract Background Genetic testing has become an important tool in the work-up of dilated cardiomyopathy (DCM), aiding in family screening and providing information about prognosis and arrhythmic risk. Nonetheless, a significant proportion of patients with DCM present negative genetic test results. The "Madrid Score" was created to evaluate the likelihood of positive genetic tests and increase their yield in DCM patients. Purpose To determine if late gadolinium enhancement (LGE) assessment can improve the Madrid Score accuracy and increase the yield of genetic tests for DCM. Methods A single-centre retrospective study of patients diagnosed with DCM who underwent cardiac magnetic resonance (CMR) and genetic test between January 2017 and October 2023. The CMR imaging included the assessment of LGE. Multivariate logistic regression was performed and the model’s change in performance was evaluated when adding LGE. Results A total of 90 patients with the diagnosis of DCM underwent CMR and genetic test during the study period. Patient’s mean age was 51.0±14.6 years, and 57.1% were male. The genetic test was positive (G+) in 42 (46.7%), and negative (G-) in 48 (53.3%) patients. A variant of uncertain significance was present in 31 (34.4%), and these were included in the G- group. Most of the known independent predictors of a G+ given by the Madrid Score were significant in our cohort: Family history of DCM (OR: 4.82; CI: 1.73-11.60; p < 0.001), absence of hypertension (OR: 0.19; CI: 0.06-0.58; p < 0.001), absence of left bundle branch block (OR: 0.22; CI: 0.05-0.98; p = 0.047), and low electrocardiogram voltage in peripheral leads (OR: 3.13; CI: 0.87-11.26; p = 0.081). When analyzing the effect of LGE in the regression model (R2 = 0.622, p < 0.001), we found that the number of LGE segments (OR: 2.54; CI: 1.10-5.90; p = 0.031), and the presence of LGE in the anterior wall (OR: 3.01; CI: 1.42-12.04; p = 0.041), were associated with a higher rate of positive genetic tests. When comparing both regression models, the incorporation of LGE increased the prediction power of the standard Madrid Score, correctly predicting 82.0% of the tests in our sample, with a probability of a G+ result ranging from 2% when all predictors were absent to 84% when ≥6 predictors, including LGE, were present. Conclusion Our study suggests that LGE assessment may enhance the Madrid Score performance and consequently improve genetic testing decisions in DCM, potentially leading to better use of the limited resources in our health care system.

Genotype predicts heart failure independent of left ventricular ejection fraction and NT-proBNP levels in hypertrophic cardiomyopathy

Abstract Background/Introduction Hypertrophic cardiomyopathy (HCM) is a myocardial disease associated with progression to heart failure. In around 40% of cases, the disease is caused by variants in genes encoding sarcomere proteins. Purpose To evaluate the role of genotype in predicting heart failure (HF) outcomes. Methods In this observational single-centre cohort study, consecutive patients with HCM were assessed for heart failure clinically stratified by genetic status into genotype-elusive which included those with no significant variants (G-) or variants of unknown significance (VUS) and genotype-positive (G+) with pathogenic/likely pathogenic (LP/P) variants. Heart failure endpoint was defined as left ventricular assist device implantation, heart transplantation or heart-failure-related death. The incidence of HF endpoint was compared between genotypes during follow-up using a time-to-event analysis. Results 474 patients (50.9 ±14.5 years, 67.3 males) with HCM (25% with left ventricular (LV) outflow obstruction) were followed for 10.9 years (IQR 5.1-13.5). G+ LP/P patients (201/474 (42.4%)) were younger (45.8. ±14.0 years) compared to G- (225/474 (47.5%), 55.2 ±13.4 years) and VUS (48/474 (10.1%), 52.0 ± 15 years); 29/474 (6.1%) reached the heart failure endpoint. The incidence of heart failure endpoints was 12.4% (25/201) in the G+ LP/P group compared to 1.5% (4/273) in the gene elusive group. A multivariate Cox proportional hazards model including NT-proBNP and LV ejection fraction (LVEF) and genetic status showed that G+ LP/P was associated with increased risk of heart failure outcomes (HR: 5.11, 95% CI: 1.43–18.25, p=0.012). Every 100-unit rise in NT-proBNP was associated with a 41% increase in risk (HR: 1.41, 95% CI: 1.20–1.66, p<0.0001). A one-unit (1%) reduction in LVEF correlated with a 10% increase in heart failure risk (HR: -0.90, 95% CI: 0.87–0.93, p<0.0001). Conclusion(s) Genetic status is a predictor of heart failure outcomes independent of LVEF and NT-proBNP levels in HCM. This underscores the importance of genetic testing in the clinical management of HCM.

Assessment of circulating biomarkers and hemodynamic response during stress to detect early cardiopulmonary complications in systemic sclerosis

Abstract Background Systemic sclerosis (SSc) is characterised by persistent immune-inflammatory system activation and excessive extracellular matrix (ECM) accumulation leading to fibrosis. Exercise Doppler Echocardiography (EDE) is a promising method to detect the early changes of fibrosis-related pulmonary and myocardial complications, like elevated left ventricular filling pressure or stress-induced pulmonary hypertension (PH). Aims The study aims to assess the linkage between the activity of fibrosis markers and abnormal exercise haemodynamics during stress in patients with SSc. Methods A total of 18 patients with SSc were enrolled in the single-centre prospective study (age 54±15,5years, 94,4 % women). SSc patients with resting PH and moderate to severe pulmonary fibrosis were excluded. According to a standardised protocol, all subjects underwent resting and exercise echocardiography on a semi-recumbent cycle ergometer with an incremental (25 watts) workload up to the maximally tolerated workload. Measurements focused on the left ventricular diastolic function (E/e’) and right ventricular haemodynamics (estimated systolic pulmonary pressure: PASP, right ventricular coupling: TAPSE/PASP, pulmonary vascular resistance: PVR). Blood samples were taken immediately before the stress test, and the Matrix Metalloproteinase-9 and 2 (MMP-9, MMP-2) levels were assessed with gelatin zymography method. Results During the EDE, PASP from baseline increased significantly (24,6mmHg±11 vs 38±16mmHg, p <0,0001), also PVR (1,2±0,49 vs 1,5±0,15 Wood unit, p<0,001) RV coupling was decreased significantly (1,2±0,68 vs 0,93±0,5, p<0,001). Left ventricular E/e’ was also increased during the stress (8,2±2 vs 10,5±5,1, p<0,05). Enzymatically active MMP-9 level was significantly correlated with RV coupling at rest and stress (p<0,05, r 0,63 at rest and r 0,52 at stress) and negatively correlated with PASP (p<0,05, r:-0,62 at rest and r -0,5 at stress). MMP-2 level only negatively correlated with resting PASP (p<0,05, r:-0,527). The left ventricular parameters did not show any relationship with MMP levels. Conclusions The level of circulating MMP-9 predicts haemodynamic behaviour during stress in SSc. MMPs could be a promising marker for detecting early changes in the right ventricle-pulmonary circulation unit.

Risk and causes of hospital admission in patients with atrial fibrillation on treatment with oral anticoagulants

Abstract Background Atrial fibrillation (AF) is associated with an increased risk of hospitalisation, although the main reasons for hospital admission and the role of antiarrhythmic drugs are not clarified. Objective The aim of our study was to assess the incidence rate and the factors associated with all-cause, cardiovascular and AF-related causes of hospitalisation in patients suffering from AF. Methods This is a prospective single-centre ongoing study (ATHERO-AF cohort) which included 2782 patients affected by non-valvular AF on oral anticoagulants. The primary endpoints were all-cause, cardiovascular and AF-related hospitalisation. Cardiac hospitalizations were defined as (non-AF) arrhythmias, acute coronary syndromes, heart failure (HF), systemic embolism, hypertensive urgency, vascular/cardiac surgery. The AF-related hospitalisation was defined as a recurrence of AF in paroxysmal pattern or as a high-rate symptomatic AF episode in persistent/permanent patterns. Multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratio (HR) with 95% Confidence interval (95%CI) for each factor in relation to risk of hospitalisation. Results Overall, 43.5% of patients were women with a mean age of 74.6±9.1year. Patients were followed for a mean of 31±26.8 months. We registered 1205 (12.1%/year) hospitalisations for any reason, 533 (5.7%/year) for cardiovascular causes and 180 (2.0%/year) were AF-related hospitalisations (Central illustration). Among the anti-arrhythmic drug use, we highlighted that flecainide and propafenone were associated with AF-related hospitalisations in paroxysmal and in persistent/permanent patterns (HR 1.861, 95%CI 1.116-3.101 and HR 1.947, 95%CI 1.069-3.548, respectively). Amiodarone (HR 3.012, 95%CI 1.835-4.943) and verapamil or diltiazem (HR 2.067, 95%CI 1.117-3.825) were associated with an increased risk of AF-related hospitalisations in persistent/permanent AF pattern. Furthermore, cancer was associated (HR 1.802, 95%CI 1.057-3.070) with increased risk of hospitalisation due to AF-related causes. Conversely, beta-blockers and digoxin were not associated with increased risk of hospital admission. Conclusions Hospitalisations of patients with AF are frequent for both cardiovascular and non-cardiovascular causes. Among the AF-related ones, the use of antiarrhythmic drugs emerged as associated with increased risk of hospitalisations, hypothesizing their poor effect in preventing AF episodes. For these reasons, we suggest carefully considering their use, reserving them for symptomatic patients with frequent AF recurrences.Central Illustration

Cardiac autonomic dysfunction in Takotsubo cardiomyopathy: an observational study

Abstract Takotsubo syndrome (TTS), commonly perceived as a benign and reversible condition has received attention due to emerging registry data revealing its prognosis to be comparable to acute coronary syndrome (ACS). Following ACS, a notable subset of patients develops autonomic dysfunction, whith unfavourable prognostic implications. Periodic repolarization dynamics (PRD) and deceleration capacity (DC), derived from ECG signals, are parameters capable of quantifying cardiac autonomic function. In this study, we aimed to assess autonomic dysfunction in patients with TTC in comparison to ST-elevation myocardial infarction (STEMI) patients. Consecutive patients diagnosed with TTS were prospectively recruited into an observational, single-centre cohort study. All patients underwent a 30-minute high-resolution ecg recording. Subsequent recordings were conducted at 4 and 12 months post-acute event. PRD and DC as markers for sympathetic and parasympathetic activity, respectively, were assessed using established methods. The control group comprised patients with STEMI. Statistical comparisons between groups were performed using the Mann-Whitney U-test, with a corrected significance level for multiple testing of α< .017. Between July 2021 and December 2023, 57 patients diagnosed with TTS were recruited (interquartile range [IQR]) 69.0 years (62.0-78.0), 98.3% women. A control group was derived from a pre-existing cohort of STEMI patients, matched through propensity score matching to adjust for age and sex (median age [IQR]: 69.0 [59.0-76.0] years, 98.3% women). At baseline, there was no significant difference in PRD between TTS patients and controls (median [IQR]: TTS: 5.28deg² [3.43-9.93], STEMI: 4.40deg² [2.24-7.21]; p = .04). However, at 4 months post-acute event, PRD was notably higher in TTS patients compared to controls (median [IQR]: TTS: 5.20deg² [2.71-8.17], STEMI: 2.63deg² [1.86-4.92]; p = .011). Interestingly, at 12-month follow-up, PRD in TTS patients did not differ from that of controls (median [IQR]: TTS: 4.55deg² [2.89-8.40], STEMI: 4.15deg² [2.42-6.85]; p = .68). Regarding DC, no significant differences were observed between TTS and STEMI patients at any time point (baseline: median [IQR]: TTS: 3.95 ms [2.27-5.51], STEMI: 3.52 ms [2.30-7.24], p = .51; 4 months: median [IQR]: TTS: 6.63 ms [4.59-8.64], STEMI: 7.41 ms [4.63-9.25], p = .39; 12 months: median [IQR]: TTS: 4.98 ms [4.19-6.67], STEMI: 7.48 ms [4.92-10.28], p = .17). Patients with TTS show substantial signs of cardiac autonomic dysfunction, similar or even higher than acute STEMI patients. This dysfunction persists even up to 4 months after the acute event, whereas STEMI patients show recovery of autonomic function in this 4 month period. DC remained consistent between TTS and STEMI patients across all time points. Further research elucidating the long-term implications of these autonomic alterations is warranted to refine risk stratification and therapeutic strategies in TTS management.

Mavacamten in a real-world hypertrophic cardiomyopathy population: how many may be eligible?

Abstract Introduction Mavacamten is a newly approved drug for obstructive hypertrophic cardiomyopathy (oHCM) and is currently being studied in non-obstructive HCM (nHCM). Our goal was to evaluate how often patients with oHCM and nHCM in a real-world cohort would be eligible for the main mavacamten trials: EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM. Methods Single-centre retrospective study enrolling consecutive patients with confirmed HCM, as per the 2023 ESC Guidelines, with at least yearly follow-up in our center, from 2017-2023. Key inclusion criteria from the three trials were considered: NYHA class II-III for all; obstructive forms (defined as peak left ventricle outflow tract [LVOT] gradient ≥50 mmHg at rest, after Valsalva manoeuvre or exercise) for EXPLORER-HCM and VALOR-HCM; left ventricular ejection fraction (LVEF) ≥55% for EXPLORER-HCM and MAVERICK-HCM; LVEF ≥60% and formal criteria for septal reduction therapy for VALOR-HCM, and NT-proBNP ≥300pg/mL for MAVERICK-HCM. Key exclusion criteria (estimated glomerular filtration rate [eGFR] <30mL/kg/1.73m2, QTc using the Fridericia’s formula >500ms, paroxysmal or intermittent atrial fibrillation present on screening electrocardiograph) were also considered. Results Overall, 410 patients were diagnosed with HCM, of whom 361 (88%) were alive at follow-up and included in the analysis: mean age of 63 ± 16 years, 196 (54%) were male, 272 (75%) with septal HCM and 60 (17%) with oHCM. According to the criteria of EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM, 35 (10%), 6 (2%) and 27 (7%) patients would be eligible for enrolment, respectively. In patients with oHCM, 35 (58%) would be eligible for the EXPLORER-HCM trial. In the overall cohort, 65 (18%) would have criteria for at least one of the trials. The main reasons for exclusion were as follows: 191 (53%) NYHA I, 43 (12%) with NYHA IV, 12 (3%) had a LVEF <55%, 8 (2%) had both HCM and infiltrative myocardial disease and/or moderate-to-severe aortic stenosis and 8 (2%) had an eGFR <30mL/kg/1.73m2. In patients with nHCM, 16 (5%) would have been excluded due to NT-proBNP <300pg/mL and 8 (3%) due to paroxysmal atrial fibrillation. Conclusion In a real-word HCM cohort, we found that approximately 1 in every 5 patients would have criteria for either of the mavacamten trials, with more than half of oHCM being potential candidates for the EXPLORER-HCM. The main reasons for non-eligibility were NYHA I and LVEF <55%.

Diastolic dysfunction and survival in patients with preserved or mildly reduced left ventricular ejection fraction

Abstract Background Left ventricular ejection fraction (LVEF) is relatively indiscriminate for prognosis in patients with preserved or mildly reduced LVEF (>40%) following myocardial infarction (MI). Aims This study sought to determine the value of guideline-based assessment of diastolic dysfunction (DD) in predicting all-cause and cardiac mortality in patients with a first-ever MI and LVEF>40%. Methods A retrospective single centre study involving 2234 patients with a first-ever MI (STEMI or NSTEMI) with LVEF>40% was performed. Clinical, angiographic, and echocardiographic data were obtained from prospectively maintained institutional databases. Outcomes data were obtained from the state-wide registry. Echocardiography was performed early post-admission for all patients. Significant diastolic dysfunction (DD) was defined as grade 2+3 diastolic dysfunction according to current American Society of Echocardiography/ European Association of Cardiovascular Imaging guidelines. Results The mean age of patients was 61.4±12.3 years, 70.7% were males, and 12.1% had 3-vessel disease. The mean LVEF was 55.8±7.2% and 9.1% had significant DD. At a median follow up of 4.5 years, there were 219 deaths (46 cardiac deaths). On Cox proportional hazards multivariable analyses incorporating significant clinical, angiographic, and echocardiographic variables, significant DD was an independent predictor of both all-cause (HR 2.01,95%CI 1.37-2.94, p<0.001) and cardiac (HR 3.97,95%CI 1.98-7.99, p<0.001) mortality. Conclusions Significant DD is an independent predictor of all-cause and cardiac mortality following MI in patients with preserved or mildly reduced LVEF and thus effectively re-stratifies prognosis in a subgroup where the LVEF is relatively indiscriminate for survival. The benefit of further investigation and/or treatment in this subgroup needs further study.

A study of intracoronary thrombolytic agents in high thrombotic burden lesions during primary PCI

Abstract Objectives High thrombus burden during Primary PCI begets worst possible outcomes, studies on adjunctive intracoronary thrombolytic agents show heterogeneous1,2 results & have limited long term follow-up. Although early studies support mechanical thrombectomy devices, larger randomized trial show that they are not able to reduce the MACE3, 4. There is no randomised clinical data for sustained mechanical thrombectomy devices till now. Purpose of the study The main purpose of this study is to analyse long term outcomes of low bleeding risk group patients undergoing Primary PCI with high thrombus burden, receiving intracoronary thrombolytic agents as an adjunctive therapy. Methods In this prospective observational single centre study, we analysed one year follow-up data of 108 consecutive primary PCI patients with high thrombus burden (G4, G5) and low bleeding risk, who were stratified into two groups basing on whether they receive intracoronary thrombolytic agent as an adjunctive agent before stent implantation. The primary outcome was NACE (Net Adverse Clinical Events, which include MACE, Death, ST/MI, major bleeding events), secondary outcomes include the individual components of the primary outcomes when analysed separately. Results The primary outcome events occurred in 21 patients (26%) in Primary stent group(PS, n=80), whereas it occurred in 2 patients(6%) in primary intra coronary thrombolysis group(PIT, n=28). Log-Rank (Mantel Cox) NACE curves show that PS group has high events when compared to PIT group(26% Vs 7%, p value – 0.042, Hazard ratio - 2.56; 95% CI - 0.76 – 8.57), there is no statistically significant difference in all other key secondary outcome event curves. Conclusion In patients presenting with STEMI, undergoing primary PCI, with high thrombus burden & low bleeding risk group, those receiving intracoronary thrombolytic agent as the adjunctive therapy before stent implantation, are able to reduce the NACE event rates during the one year of follow-up.Fig1:Log Rank (Mantel Cox) NACE curve

Clinical evidence of pacemaker implantation during gestation: a case series

Abstract Background Although recommended avoid any intervention during gestation in cases of poor tolerance to high degree atrioventricular block, pacemaker implantation may be necessary in pregnant women. Purpose To present outcomes of pacemaker implantation during gestation. Methods This prospective, single center study included 10 cases of pacemaker implantation during gestation (median age of patient - 26 years old at 18 weeks of gestation). We evaluated the further course of gestation and obstetric outcomes after implantation in comparison with pregnant with tachyarrythmias (n=111). Results Among 121 pregnant women with varying arrhythmias high degree atrioventricular block was detected in 10 cases (8,3%). In 6 cases this bradyarrhythmia diagnosed for the first time in gestation (60%). All pregnant with high degree atrioventricular block had clinical signs: dizziness and weakness (100%), syncope (70%), episodes of low blood pressure (100%). Pacemaker implantation performed due to hemodynamic instability and poor tolerance of bradyarrhythmia in all cases. Using electroanatomical mapping (Ensite Precision system)and echocardiographic guidance helped to reduce fluoroscopy time. For one pregnant implanted leadless pacemaker (Micra) with achieved more than 80% atrio-ventricular synchronization. Outcomes: further course of gestation characterized by increased incidence of uterine contractile activity (30%) in cases of high degree atrioventricular block, that was significantly higher than in pregnant with tachyarrhythmias (2%) (p=0.007). There were no differences in the rate of other complication: uterine blood flow violation (20% vs 12%, p=0.520), placental abraption (10% vs 5%, p=0.237) and preeclampsia (10% vs 5%, p=0.237). Vaginal type of delivery was in the majority of cases in both groups (70% vs 86%, p=0.553). Neonatal outcomes characterized with normal range of fetal birth weight (median 3163 vs 3212 grams, p=0.981) and 5 minute Apgar score (median 8.6 vs 8.7, p=0.564). There was no incidence of maternal and fetal mortality. In 12 month follow-up all patient have optimal electrical parameters of devise and remained stable over time. Conclusions High degree atrioventricular block in pregnant characterized by increased rate of uterine contractile activity. Pacemaker implantation during gestation can be effectively performed and associated with benign outcomes.

Prognostic significance of right ventricle to pulmonary artery coupling acute improvement after mitral transcatheter edge-to-edge repair

Abstract Background Transcatheter Edge-to-Edge Repair (TEER) of mitral valve is a valid treatment option for severe mitral regurgitation. The right ventricle is acutely affected by early hemodynamic changes following the correction of significant mitral regurgitation. Echocardiographic parameters of the right chambers could have a prognostic impact even in a periprocedural setting. In particular, right ventricle to pulmonary artery coupling improvement may be of pivotal importance, as this parameter is a validated marker of right ventricle function. Purpose To evaluate the prognostic impact of early improvement of right ventricle to pulmonary artery coupling assessed by means of the Tricuspid Annular Plane Systolic Excursion/Pulmonary Artery Systolic Pressure (TAPSE/PASP) ratio after TEER. Methods This retrospective single centre study included patients treated with TEER in our hospital from 2015 to 2023. Transthoracic echocardiography was performed before and shortly after device positioning. Acute effects of TEER on echocardiographic parameters were assessed by paired samples t-test. Diagnostic accuracy of the percent variation in the TAPSE/PASP ratio was assessed by means of receiver-operating characteristics analysis. Prognosis was evaluated by Kaplan-Meier analysis. Results The study included 95 patients (age 78 ± 10 years; 63% men; BMI 25 ± 5 kg/m2) with severe or moderate-to-severe mitral regurgitation. Mean baseline Left Ventricle (LV) ejection fraction was 45 ± 16%, LV end-diastolic volume was 157 ± 62 ml and effective regurgitant orifice area was 41 ± 25 mm2. Post-procedural echocardiographic assessment showed early improvement of LV end-diastolic diameter (p < 0.001), LV end-diastolic volume (p = 0.025), LV stroke volume (p < 0.001), LV global longitudinal strain (p < 0.001), right ventricle free wall longitudinal strain (p < 0.001) and PASP (p = 0.002). Percent improvement of TAPSE/PASP ratio showed a sufficient diagnostic accuracy in predicting a composite outcome of hospitalisation for heart failure and all cause mortality at 1 year (area under the curve 0.66, p = 0.047), with an optimal cut-off of 5.5%. An improvement of the TAPSE/PASP ratio over this threshold was associated with a reduction in the composite outcome (hazard ratio 0.38, p = 0.045). Conclusion TEER improves both left and right ventricular dynamics, which can be detected with echocardiography. In particular, an acute improvement of the TAPSE/PASP ratio is associated with an improvement in short-term prognosis. A comprehensive assessment of right ventricular function, including TAPSE/PASP ratio, should be routinely performed before and after TEER.

A novel marker of cardiovascular risk stratification: the role of total cardiovascular calcium score using cardiac CT

Abstract Introduction It is widely accepted that coronary and valve calcification measured by cardiac CT, individually, are associated with cardiovascular events and mortality. However, the role of an encompassing marker of cardiovascular atherosclerosis could be more representative of the real cardiovascular risk. Objectives To determine the prognostic value of a combined coronary, valvular and aortic calcium score to predict long-term major adverse cardiac and cerebrovascular events (MACCE). Methods We conducted a single center study on 316 consecutive patients who underwent cardiac CT scan between January 2018 and December 2019. We excluded patients with poor imaging quality, constrictive pericarditis, prosthetic valves and/or devices. The calcium score of coronary arteries (CA), mitral valve (MV), aortic valve (AoV), ascending aorta (AAo) and aortic arch (AAc) were calculated from non-contrast ECG-gated CT using the Agatston method and were combined to derive a valvular (VA=MV+AoV), total cardiac (TC=CA+VA) and total cardiovascular (TCV=TC+AAo+AAc) calcium scores (Fig.1A). The primary endpoint was a composite of MACCE, defined as all-cause death, stroke, myocardial infarction and hospital admission for heart failure. Results A total of 275 CT scans were suitable for analysis. Mean age was 59.6±12.3 years, 48.4% were female. A total of 183 (66.7%) patients presented calcification in at least one location. Patients with calcification on any of the prespecified locations had higher prevalence of hypertension, dyslipidemia and type 2 diabetes mellitus (DM) than those without any calcium (p<0.05). After a median follow-up of 3.18 [IQR 2.84-3.69] years, 40 (14.5%) patients had met the primary endpoint. Regression analyses demonstrated that all CA, VA, TC and TCV scores were independent predictors of MACCE (p<0.05 for all). The best prediction models included calcium score (all combinations), age, sex, type 2 DM and smoking status (Fig.1B). The model with TCV score was the most powerful predictor of MACCE (χ2 47.8), followed by TC score (χ2 43.1). Of interest, the model with CA score had the poorest performance (χ2 35.4). Conclusion Coronary calcium score is a quick way to stratify risk in clinical practice, but its performance is too focused on coronary events. Total cardiovascular calcium score, however, is more encompassing, also quick to measure, and a more truthful depiction of the patient’s cardiac and cerebrovascular risk, potentially allowing a more tailored and timely approach to risk factors in clinical practice.

Long-term survival after coronary artery bypass grafting comparing bilateral versus single internal mammary artery in a women cohort

Abstract Introduction Although neutral results from the ART randomized controlled trial, observational studies have been supporting better survival after bilateral internal mammary artery (BIMA) vs single internal mammary artery (SIMA) coronary artery bypass grafting (CABG). However, for some specific subgroups, like women patients, more doubts remain about BIMA benefits. Aim To compare long-term survival and early results in women after SIMA vs BIMA. Methods Longitudinal, retrospective, single-center study including consecutive women with at least 2 left-coronary system (LCS) vessel disease who underwent primary isolated CABG with at least 1 internal mammary artery (IMA) conduit and a minimum of 2 conduits targeting the LCS, between 2004-2014. Emergent or salvage surgeries, on-pump beating-heart, BIMA in which 1 IMA targeted the right coronary artery territory were excluded. The primary outcome was all-causes mortality (checked on February 2023). Time-to-event outcomes were studied using Kaplan-Meier Curves, Log-Rank test and multivariable Cox Regression. Median follow-up was 11 years, maximum of 19 years. Results From 539 women selected for this study, BIMA CABG was performed in 30%. SIMA patient’s were older (mean age 68.95±8.39 vs 62.75±9.82 years, p<0.001), but the prevalence of cardiovascular risk factors were similar between groups (arterial hypertension, p=0.693; dyslipidemia, p=0.111; diabetes mellitus, p=0.462 and obesity, p=0.109). Peripheral artery disease (p=0.707), left ventricular dysfunction (p=0.727), cerebrovascular disease (p=0.730), active smoking habits (p=0.05) and chronic obstrutive pulmonary disease (p=0.537) were also similar. Severe chronic kidney disease (27% vs 14%, p<0.001) and Canadian Coronary Society - grade IV (74% vs 63%, p=0.011) were more frequent in SIMA group. In the univariable survival analysis, SIMA had worse survival results than BIMA (Log Rank test p<0.01). At 5-, 10- and 15- years of follow-up, cumulative survival for SIMA vs BIMA were 88% vs 90%, 68% vs 75%, 42% vs 58%, respectively. However, the multivariable Cox regression showed that BIMA was not associated with long-term survival (HR [95%CI]: 1.09 [0.75-1.59], p=0.6). Most of post-operative outcomes were similar between groups, with the exception of atrial fibrilation (25% vs 16%, p=0.031) and time to discharge (median days [min-max]: 7 [4-128] vs 7 [4-59]) that were higher in SIMA. No differences were found in immediate reexploration of thorax (sternal infection – 0.3% SIMA vs 1.2% BIMA, p=0.219; bleeding- 1.6% SIMA vs 0.6% BIMA, p=0.681). Redo CABG occurred in 1 SIMA and 1 BIMA women, at 41 and 84 months of follow-up, respectively. Conclusion In this study, revascularization with BIMA seems to be safe in women and provides similar results than SIMA. More studies in women are needed to establish the better approach for this specific subgroup.

Single arterial access versus standard access in TAVI: results from a large multicenter registry

Abstract Background The transfemoral approach has become the gold standard primary access for transcatheter aortic valve implantation (TAVI) due to low complication rates. An additional secondary access (ScA) is used for angiographic guidance of the procedure. Recently, small, single-center studies demonstrated feasibility of single-access for transfemoral TAVI without a secondary access. However, comparative and large-scale data are missing. Purpose We assessed vascular and bleeding complications of ScA and Single access (SA) approaches in a large multicenter registry to evaluate both strategies. Methods The PULSE registry (Plug or sUture based vascuLar cloSurE after TAVI) retrospectively evaluated data of 10,120 patients who underwent transfemoral TAVI at 10 high-volume German heart centers from 2016 to 2021. In 9,457 patients who qualified for analysis ScA (80.7% femoral, 19.3% radial) were performed in 8709 (92%) and SA in 748 (8%). Outcomes were evaluated in accordance with the Valve Academic Research Consortium (VARC-3) definitions. Results Median age was 81.9[IQR 78.2, 85.1] years and 48.9% of patients were female (median logistic EuroSCORE II: 3.3% [IQR 2.1, 5.6]). Peripheral artery disease was comparable between groups (13.5 vs. 14.0%, p=0.73). While overall major access-related vascular complications did not differ significantly (6.1% vs. 4.8%, p=0.20), there was a higher incidence of minor complications for ScA compared to SA (9.0% vs. 2.8%, p<0.001). Secondary access complications amounted to 2.7% in the ScA group and were mainly characterized as bleeding (1.2%) and pseudoaneurysms (1.2%) mostly treated conservatively (1.2%), yet in some cases surgical repair was needed (0.8%). No significant difference was observed regarding type III/IV bleeding (4.1% vs. 4.3%, p=0.91), stroke rate (2.4% vs. 3.6%, p=0.05), stage III/IV acute kidney injury (2.4% vs. 2.4%, p=1.00) or all-cause 30-day mortality (5.8% and 5.7%, p=0.99) for ScA compared to SA groups. Conclusion In patients treated with transfemoral TAVI, a single access approach was associated with lower rates of minor access-related vascular complications without compromising overall outcomes, suggesting potential benefits of a minimally-invasive TAVI approach with the omission of additional vascular access.

Intracoronary nicardipine to induce hypaeremia

Abstract Background Several pharmacological agents and routes of administration have been used to induce transient maximal hyperaemia, but most suffer from shortcomings that limit their clinical usage. Nicardipine, a dihydropyridine calcium channel blocker, has been proposed as a coronary hyperaemic agent with the advantage of not causing any adverse effects. Purpose We compared intracoronary (IC) nicardipine with IC papaverine for obtaining fractional flow reserve (FFR) and pullback pressure gradient (PPG). Methods and results This is a prospective, single-center study enrolling stable patients presenting with intermediate coronary artery disease (CAD) undergoing invasive functional assessment. The lowest FFR, duration of the hyperemic plateau, and PPG were assessed after IC nicardipine (400 µg to the left coronary or 300 µg to the right coronary artery) and IC papaverine (12 mg to the left coronary artery and 8 mg to the right coronary artery). Results Overall, 107 patients with 108 vessels (216 FFR and 216 PPG paired measurements) were analyzed. The correlation in FFR between nicardipine and papaverine was r = 0.95 (95% CI 0.92 to 0.96, p < 0.001) with a mean difference of 0.02 FFR units (limit of the agreement [LOA]: -0.04 to 0.08). Similarly, the correlation in PPG between nicardipine and papaverine was r = 0.86 (95% CI 0.71 to 0.93, p < 0.001) with a mean difference of 0.01 PPG units (limit of the agreement [LOA]: -0.14 to 0.17). The hyperaemic plateau was significantly longer with nicardipine (101.4 ± 62.1 s nicardipine vs 41.5 ± 14.3 s papaverine, p < 0.001). No significant differences were observed in the magnitude of changes in blood pressure and heart rate (p=NS). No complications occurred with the administration of IC nicardipine or papaverine. Conclusion FFR and PPG values obtained following nicardipine administration exhibited excellent agreement with those obtained using papaverine. Moreover, the hyperaemic response induced by nicardipine led to a significantly prolonged steady state in comparison to papaverine. Given its widespread availability, cost-effectiveness, safety profile and frequent utilization in clinical settings, nicardipine emerges as the optimal vasodilator for coronary physiology testing.FFR by Nicardipine vs PapaverinePPG by Nicardipine vs Papaverine

Impact of a prehospital mobile cloud ECG transmission system on door-to-balloon time, myocardial damage and mid-term all-cause mortality in patients with ST-elevation myocardial infarction

Abstract Background Guidelines recommend to establish a regional reperfusion strategy to maximize the efficiency of care for patients diagnosed with ST-elevation myocardial infarction (STEMI). In Addition, the recently developed mobile cloud-based 12-lead electrocardiogram (ECG) transmission system enables the transmission of prehospital ECGs at a low cost. Medical staff can use electronic devices to access and review ECGs from anywhere. However, the effectiveness of the prehospital mobile cloud ECG system has not yet been clearly established. Objective This single-center study aims to evaluate the impact of the prehospital mobile cloud ECG system on reducing Door-to-Balloon Time (DTBT), myocardial damage, and mid-term all-cause mortality in patients with STEMI. Methods In June 2018, eight prehospital Mobile Cloud ECG Transmission systems were integrated into the regional Emergency Medical Service (EMS) in our region. This study examined and compared Door-to-Catheterization Laboratory Time (DTCT), DTBT, Onset-to-Reperfusion Time (OTRT), peak creatine kinase-MB (CK-MB) levels, and one-year mortality rates of STEMI patients in the five years before and after introducing the prehospital mobile cloud ECG system. From June 2013 to May 2023, our institute received a total of 426 STEMI patients via ambulances from these two EMS departments. After excluding 23 patients with OTRT exceeding 24 hours and 76 patients who were transferred without the system post-introduction, 327 consecutive STEMI patients who underwent emergency percutaneous coronary intervention (PCI) were included in the study. The patients were divided into two groups: 169 patients before the prehospital mobile cloud ECG system introduction and 158 patients after that. Results There were no significant differences in age, gender, past medical history, and Killip Class IV between the two groups, except for the proportion of left main trunk (LMT) lesions, which was significantly higher in the ECG group. Significant reductions were observed in both DTCT and DTBT in the group after introduction, with differences noted as (DTCT: 42 min vs. 26 min; p < 0. 001, and DTBT: 74 min vs. 56 min; p < 0.001, respectively). However, the OTRT did not show a significant difference. Peak creatine kinase-MB (CK-MB) levels did not differ between the two groups, and Kaplan-Meier analysis revealed no significant difference in one-year mortality between them. Multivariate Cox regression analysis, which included variables such as age, peak CK-MB levels, Killip Class IV, LMT lesions, OTRT and the prehospital mobile cloud ECG transmission system usage, revealed that only Killip Class IV was significantly associated with one-year mortality (hazard ratio of 2.82 and a 95% confidence interval of 1.61-4.94; p=0.0003). Conclusion The prehospital mobile cloud ECG transmission system significantly reduced DTBT, but did not lead to a reduction in myocardial damage or an improvement in mid-term prognosis.Effect of the ECG Transmission SystemKaplan-Meier analysis

O2 consumption overshoot in patients with heart failure: crossing the line

Abstract Background Cardiopulmonary exercise testing (CPET) is among the most valuable clinical tools for evaluating disease severity and physical activity limitations in heart failure (HF) patients. Peak oxygen uptake (pVO2) reflects maximal cardiac output during exercise, and it is considered a major parameter in selecting candidates for cardiac transplantation. VO2 overshoot, a transient increase in VO2 during recovery from maximal exercise, has been frequently observed in HF patients and is attributed to the transient increase in cardiac output caused by the mismatch between cardiac contractility and afterload reduction. However, the prognostic significance of this phenomenon remains to be fully established. Purpose This study aimed to characterize the prognostic significance of VO2 overshoot following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF, with left ventricular ejection fraction (LVEF) <50%, who underwent CPET between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sitting passively for 2 minutes). VO2 overshoot kinetics during recovery were measured and described as the time until post-exercise VO2 fell below pVO2 for at least 15 seconds. Please refer to Figure 1A for an example of normal and prolonged VO2 overshoot. The study endpoint was time to cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) over 1-year follow-up. Results A total of 254 patients were included (mean age 59 ± 12 years; 83% males; mean LVEF 34 ± 9%; 70% with ischemic HF; 77% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean predicted pVO2% 52 ± 16%; mean VE/VCO2 slope 41 ± 13). The VO2 overshoot had a normal distribution (Figure 1B) and lasted on average for 45 ± 33 seconds. There were no differences between patients that had an overshoot higher and below average. Overall, during follow-up, 25 patients met the composite endpoint (12 CV deaths, 9 urgent heart transplants, and 4 LVAD). Univariate analysis showed a significant relationship between VO2 overshoot and the outcome of interest (HR 1.01, 95% CI 1.00 – 1.02, p=0.027). In multivariate analysis, this association remained significant, even after adjusting for pVO2 and VE/VCO2 slope (HR 1.01, CI 95% 1.00– 1.02, p=0.026). Conclusion This study delves into the intriguing phenomenon of VO2 overshoot in patients with heart failure, shedding light on its potential prognostic significance. The independent association between VO2 overshoot and the composite endpoint suggests that this transient increase in oxygen consumption may carry prognostic value. Further studies should confirm these findings.

Exercise stress testing recovery kinetics: the forgotten phase

Abstract Background Impaired exercise capacity is a cardinal feature of heart failure (HF). Peak oxygen uptake (pVO2) and ventilatory efficiency (VE/VCO2 slope) during exercise are well-consolidated prognostic markers in patients with HF. A previous study suggested that abnormally prolonged VO2 recovery, specifically the failure to decrease VO2 from peak exercise by 10.5 mL/kg/min at 180 seconds of the recovery phase, predicts adverse outcomes in HF. However, it is unknown to what extent the recovery of VEqCO2, a marker of ventilation/perfusion mismatch, adds prognostic value to the already existing parameters. Purpose The aim of this study was to characterize the functional and prognostic significance of VEqCO2 kinetics following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF with left ventricular ejection fraction (LVEF) <50% who underwent cardiopulmonary exercise testing (CPET) between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sittng passively for 2 minutes). VO2 and VEqCO2 kinetics during recovery, described as the absolute difference to peak VO2 (difVO2) and VEqCO2 (difVEqCO2), were measured at 30, 60, 120, and 180 seconds. Outcomes were assessed as a composite of cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) implantation at 1 year. Results A total of 238 patients were included (mean age 58 ± 12 years; 82% males; mean LVEF 34 ± 10%; 68% with ischemic HF; 75% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean VE/VCO2 slope 41 ± 12). During the 1-year follow-up, 19 patients met the endpoint (8 CV deaths, 8 urgent heart transplants, and 3 LVAD). ROC curve analysis showed that the best correlation between difVEqCO2 and outcomes was apparent at difVEqCO2 of 180 seconds (AUC 0.83) with a cut-off value of 1 (sensitivity 93%, specificity 58%). These patients, who had a decrease in VEqCO2 (difVEqCO2 >1) at 180 seconds, were significantly older (p=0.02), had a lower LVEF (p<0.001), and higher NYHA (p<0.001). They were at an increased risk of cardiovascular events compared to those with an increase in VEqCO2 (difVEqCO2 <1) at 180 seconds (event-free survival at 1 year 86% vs. 98%, log-rank p<0.001). In multivariate analysis, the statistical association between difVEqCO2 and outcomes remained significant, even after adjusting for difVO2 at 180 seconds (HR 4.315, CI95% (1.349-13.804), p=0.014). Conclusion Abnormal VEqCO2 kinetics in the recovery period of CPET is an easily recognizable non-invasively derived measurement that predicts outcomes in HF. VEqCO2 may complement the evaluation of VO2 and other parameters during recovery to further improve prognostic risk stratification in HF.

Progression of myocardial fibrosis is the major determinant of heart failure hospitalization in patients undergoing transcatheter aortic valve implantation

Abstract Background Patient who are hospitalized for heart failure (HF) prior to transcatheter aortic valve implantation (TAVI) are associated with poor prognosis. In this study, we aimed to assess whether myocardial fibrosis (MF) in TAVI patients is strongly involved in prior heart failure hospitalization. Methods We performed a retrospective single-center study, including 93 patients who underwent cardiac biopsies before TAVI from December 2022 to December 2023. The extent of MF was assessed on Masson’s trichrome-stained tissue specimens, using a validated software "ImageJ". Results Prior hospitalization had significant association with BNP (HF hospitalization (+): 461.9[130.4-987.7] vs. HF hospitalization (-):125.3[78.2-228.6], p=0.0014) , aortic valve area index (AVAi) (0.43±0.02 vs. 0.51±0.01, p=0.002), left ventricular ejection fraction (LVEF) (54.4±2.8 vs. 67.2±1.6, p=0.0002), E/e’ (23.4±1.9 vs. 19.1±1.0, p=0.045), left atrial volume index (LAVI)(59.0±3.5 vs. 46.1±1.6, p=0.0013), global longitudinal strain (GLS) (13.2±1.0 vs. 15.7±0.5), and percent area of myocardial fibrosis(7.0[4.8-14.2] vs. 3.3[2.2-7.3], p=0.0002) Moreover, percent area of MF was the most reliable indicator (area under the curve: AUC= 0.75, p=0.0009) of prior heart failure hospitalization (figure 1) among HF parameters which include BNP (AUC=0.73, p<0.0001), AVAi (AUC=0.69, p=0.0024), LVEF(AUC=0.68,p=0.0005), E/e’ (AUC=0.63, p=0.051), LAVI (AUC=0.72, p=0.0022), GLS (AUC=0.65, p=0.035). Furthermore, the ROC curve analyses demonstrated that the best thresholds of LVEF and percent area of MF were 64.9% (60.9% sensitivity and 68.1% specificity) and 4.1% (91.7% sensitivity and 56.5% specificity) for heart failure hospitalization, respectively. When patients were divided into 4 groups according to LVEF 65% and percent area of myocardial fibrosis 4%, a stepwise increase in the proportion of heart failure hospitalization was found in the 4 groups (figure 2). Conclusions This study illustrates that extensive myocardial fibrosis was strongly associated with prior heart failure hospitalization in TAVI patients. Patients with advanced myocardial fibrosis due to aortic stenosis may benefit from earlier treatment with TAVI to prevent further progression of myocardial fibrosis.

Significant correlation between the extent of myocardial fibrosis and heart failure parameters in patients undergoing transcatheter aortic valve implantation

Abstract Background Recent studies have demonstrated that the prognosis of patients undergoing transcatheter aortic valve implantation (TAVI) is determined by the presence of myocardial fibrosis. The aim of this study was to quantify myocardial fibrosis in tissues obtained through myocardial biopsy before TAVI and to evaluate the relationship between the extent of myocardial fibrosis and baseline cardiac parameters. Methods We performed a retrospective single-center study, including 93 patients who underwent cardiac biopsies before TAVI from December 2022 to December 2023. The extent of myocardial fibrosis was assessed on Masson’s trichrome-stained tissue specimens, using a validated software "ImageJ". Results Median percent area of myocardial fibrosis in the entire cohort was 4.7% (interquartile range: 2.5 - 7.9). A significant correlation was found between the extent of myocardial fibrosis and brain natriuretic peptide (r= 0.41 p=0.0001), left ventricular ejection fraction (r=0.34, p=0.0009), aortic valve area index (r=0.33, p=0.0017), and global longitudinal strain (r=0.52, p<0.001). Patients who experienced prior heart failure hospitalization had a significantly larger extent of myocardial fibrosis (3.3% vs. 7.0%, p=0.0002). Conclusions Extensive myocardial fibrosis was associated with various heart failure parameters in patients undergoing TAVI. Patients with a large extent of myocardial fibrosis may require early intervention and/or intensive heart failure medical therapy to prevent fibrosis progression.

Single center experience of internal jugular vein as alternative access for implantation of a wireless pulmonary artery pressure sensor

Abstract This single-center study delves into the novel use of the internal jugular vein (IJ) as an alternative access pathway for the implantation of the CardioMEMS device, a wireless pulmonary artery pressure sensor. This approach is compared to the conventional femoral vein access in terms of procedural times, contrast volume, and patient outcomes. The study spans five years, from 2018 to 2023, evaluating the efficacy and safety of IJ access for CardioMEMS implantation. The analysis revealed a tendency towards shorter procedural times and reduced contrast volume with IJ access, although statistical significance was not reached due to the small sample size. Notably, IJ access provided a quicker needle-to-door time, suggesting benefits such as improved patient throughput and potentially shorter hospital stays, which are pivotal in a healthcare landscape that prioritizes efficiency and cost-effectiveness. In conclusion, this investigation offers initial evidence that IJ vein access is a feasible and potentially superior alternative for CardioMEMS device implantation. While the findings are preliminary due to the study's limited scale, they pave the way for future larger-scale, multicenter studies. Such research could confirm the benefits of IJ access and possibly influence clinical practices, enhancing the management of heart failure patients.