Multicenter Registry Research Articles

Left Atrial Appendage Closure in Atrial Fibrillation Patients with Cancer

Background: There are limited data about left atrial appendage closure (LAAC) in patients with cancer. We therefore sought to compare the outcome after LAAC in patients with vs. without cancer in a multicentre registry. Methods: In this sub-analysis of the prospective Austrian LAAC Registry, we analysed consecutive patients undergoing LAAC to assess the relationship between baseline characteristics and outcome in patients with vs. without cancer. Inverse probability weighting was performed to adjust for differences in baseline characteristics. Results: A total of 486 consecutive patients from 9 centres with a median age of 75 years (IQR 70–79 years; 35.8% female) were included. Fifty-seven patients (11.7%) had a history of cancer. The median CHA2DS2-VASc and HAS-BLED scores were similar in both groups (median [IQR], 4 [4–6] vs. 5 [3–5], p = 0.415; 4 [3–4] vs. 3 [3–4], p = 0.428 in cancer vs. other patients). Cancer patients were significantly older, and anaemia and gastrointestinal bleeding were significantly more common. Major procedural complications occurred in 5.3% vs. 7.0% (p = 0.276) of patients. The cumulative five-year survival rates were 80.7% and 84.8% in cancer vs. other patients (adjusted hazard ratio for death 1.29 [95% CI 0.67–2.48], p = 0.443). There were also no differences in one-year survival (96.1% vs. 94.0%, p = 0.582) and five-year event-free survival (64.9% vs. 74.4%, p = 0.124). Conclusions: In daily clinical practice, LAAC has already been accepted as a treatment option in patients with cancer. This retrospective analysis shows that short-term and adjusted long-term complications are similar in patients with vs. without cancer undergoing LAAC.

Combined analysis of the MF18-02/MF18-03 NEOSENTITURK studies: ypN-positive disease does not necessitate axillary lymph node dissection in patients with breast cancer with a good response to neoadjuvant chemotherapy as long as radiotherapy is provided.

The omission of axillary lymph node dissection (ALND) remains controversial for patients with residual axillary disease after neoadjuvant chemotherapy (NAC), regardless of the residual burden. This study evaluated the oncologic safety and factors associated with outcomes in patients with residual axillary disease. These patients were treated solely with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD), without ALND, after NAC. A joint analysis of two different multicenter cohorts-the retrospective cohort registry MF18-02 and the prospective observational cohort registry MF18-03 (NCT04250129)-was conducted between January 2004 and August 2022. All patients received regional nodal irradiation. Five hundred and one patients with cT1-4, N1-3M0 disease who achieved a complete clinical response to NAC underwent either SLNB alone (n=353) or TAD alone (n=148). At a median follow-up of 42 months, axillary and locoregional recurrence rates were 0.4% (n=2) and 0.8% (n=4). No significant difference was found in disease-free survival (DFS) and disease-specific survival (DSS) rates between patients undergoing TAD alone versus SLNB alone, those with breast positive versus negative pathologic complete response, SLN methodology, total metastatic LNof one versus ≥2, or metastasis types as isolated tumor cells with micrometastases versus macrometastases. In the multivariate analysis, patients with nonluminal pathology were more likely to have a worse DFS and DSS, respectively, without an increased axillary recurrence. The omission of ALND can be safely considered for patients who achieve a complete clinical response after NAC, even if residual disease is detected by pathologic examination. Provided that adjuvant radiotherapy is administered, neither the SLNB method nor the number of excised LNs significantly affects oncologic outcomes.

Association of BMI with adherence and outcome in heart failure patients treated with wearable cardioverter defibrillator.

Obesity is a known risk factor for cardiovascular disease (CVD), yet an 'obesity paradox' has been observed in various CVD contexts. The impact of obesity on heart failure (HF) patients treated with a wearable cardioverter-defibrillator (WCD) remains underexplored. In a multicentre international registry, we retrospectively collected data from a consecutive series of 1003 patients. These patients were divided into three body mass index (BMI) groups: <25kg/m2 (n=348), 25-30kg/m2 (n=383), and >30kg/m2 (n=272), with BMI>30kg/m2 defined as the reference category. Demographics, indications, adherence, WCD shocks, arrhythmic events, rehospitalization due to cardiovascular causes, and mortality were analysed. At 3month follow-up, patients with a BMI>30 showed the greatest improvement in left ventricular ejection fraction (LVEF) at 51.4%, significantly higher than the 41.4% in those with a BMI<25 (P=0.017) and comparable with the 49.4% in the BMI 25-30 group (P=0.635). WCD wearing time and adherence were similar across all BMI groups. The incidence of WCD shock was similar across BMI groups. Rates of ventricular tachycardia (VT), ventricular fibrillation and non-sustained VT (ns-VT) were comparable across BMI groups. The rate of implantable cardioverter-defibrillator (ICD) implantation was 40.3% across all patients, with a slightly lower rate in the BMI>30 group (36.8%) compared with others, although not significantly. Rehospitalization due to cardiovascular causes was significantly lower in the BMI>30 group (55.4%) compared with the BMI 25-30 group (70.9%; P=0.048), but similar to the BMI<25 group (54.9%; P=0.957). At 2year follow-up, mortality was lower in the BMI>30 group (5.9%) compared with the BMI<25 (7.5%; P=0.029) and BMI 25-30 groups (7%; P=0.681). In multivariable analysis, LVEF at long term was significantly associated with a reduction in mortality. Obese patients exhibited significantly greater improvement in LVEF, which was associated with reduced mortality. Adherence to WCD therapy was excellent across all BMI groups. ICD implantation occurred in 40.3% of patients, with similar WCD shock rates and arrhythmic events across BMI groups. An obesity paradox was observed, with obese patients demonstrating significantly lower rehospitalization rates due to cardiovascular causes and reduced mortality at follow-up.

Evolving use and clinical outcomes of coronary intravascular lithotripsy: insights from an international, multicentre registry

BackgroundIntravascular lithotripsy (IVL) is increasingly used for treatment of coronary artery calcification. This study aimed to evaluate contemporary utilisation patterns, safety and efficacy of IVL in an unselected real-world patient cohort.MethodsWe included 454 patients undergoing IVL from May 2019 to February 2024 across seven centres in two European countries. Key endpoints included device success, technical success, procedural success, IVL-related complications and major adverse cardiovascular events (MACE) at 1-year follow-up.ResultsThe cohort (mean age 73±9 years, 75% male) had a mean SYNTAX Score of 22.0±13.6. Device, technical and procedural success were achieved in 98%, 91% and 89% of patients, respectively. IVL-related complications occurred in six patients (1%). At 1-year follow-up, MACE was observed in 37 patients (13%). Over time, IVL use increased in patients with acute coronary syndrome (p=0.004) and in combination with intracoronary imaging (p=0.002), while use of other calcium modification devices decreased (p=0.034).ConclusionIn this real-world registry, IVL demonstrated efficacy across diverse clinical and anatomical settings. High success rates, low complication rates and MACE rates were observed acutely and at 1-year follow-up. Utilisation patterns evolved over time, with increased adoption in acute scenarios and alongside intracoronary imaging.

Venous aneurysms in unruptured supratentorial brain arteriovenous malformations: a protective factor against hemorrhagic stroke and insights into hemodynamic mechanisms.

This study endeavors to clarify the impact of venous aneurysms (VA) on hemorrhagic risk in brain arteriovenous malformations (AVMs) and uncover potential hemodynamic mechanisms, utilizing quantitative digital subtraction angiography (QDSA) technology and survival dataset. Patients were enrolled in a multicenter prospective collaboration registry between August 2011 and August 2021, and subsequently categorized into the VA and non-VA cohorts. Using propensity score-matched survival analysis, we quantitatively assessed the natural risk of hemorrhagic stroke in these two cohorts. Additionally, a quantitative hemodynamic analysis was conducted to explore the distinctions in hemodynamic characteristics between these two cohorts. Among 3758 consecutive AVMs documented at a single center from the registry, 820 unruptured AVMs who maintained conservation management over 1 month were identified. Following a two-step matching process, 504 cases were retained for survival analysis and 408 cases for hemodynamic analysis. Overall, the presence of VA emerged as a protective factor, associated with a decreased risk of hemorrhagic stroke (HR, 0.21 [95% CI: 0.07-0.62], p = 0.004). Distinct hemodynamic characteristics were observed in AVMs with VA, showing a lower stasis index in two components of AVMs-the nidus (p = 0.014) and the main draining vein (p = 0.018). In this observational prospective cohort study, the presence of VA is associated with a decreased risk of hemorrhagic stroke in AVMs, suggesting an underlying hemodynamic mechanism involving the redistribution of excessive pressure loads within the AVM nidus by the VA. Questions What impact, if any, does VA have on the hemorrhagic risk in brain AVMs? Findings Presence of VA is associated with a decreased hemorrhagic stroke risk through the redistribution of pressure loads. Critical relevance VA in brain AVMs emerges as a protective factor against hemorrhagic stroke. Understanding this association and the underlying hemodynamic mechanisms offers valuable guidance for preventive strategies and informs clinical decision-making, improving overall patient care.

Impact of SAPIEN3 Ultra RESILIA on improvement of valve performance: Insights from the multicenter registry: a propensity-score matched analysis

Abstract Backgrounds: Transcatheter aortic valve implantation (TAVI) is now a cornerstone treatment for symptomatic severe aortic stenosis across all risk profiles, including low-risk and younger patients. As such, the performance and durability of transcatheter heart valves (THVs) are paramount. SAPIEN3 Ultra RESILIA (S3 UR) is expected to improve hemodynamics compared with SAPIEN3 (S3) due to the use of RESILIA bovine pericardial tissue and modified sawing maneuvers for each of three leaflets in 20 and 23mm valves. Aim The aim of study was to evaluate the hemodynamic improvement with S3 UR compared to S3 who underwent TAVI. Methods In a multicenter TAVI registry, we identified 1,931 patients who received a balloon-expandable valve over the past three years. We focused on post-procedural effective orifice area (EOA), post-procedural indexed EOA (EOAi), incidence of prosthesis-patient mismatch (PPM), paravalvular leakage (PVL) and post-procedural mean pressure gradient (mean PG) as our primary endpoints. We preformed propensity score matching analysis using a 1:1 ratio. Parameters including aortic stenosis severity, % oversizing and post dilatation were incorporated into the matching model. Results Of patients, mean age was 84 years old and 37.9% were male. EOAi was significantly larger in S3 UR group than in the S3 group for both cohorts [overall cohort: 1.21 (1.02 – 1.36) vs. 1.08 (0.93 – 1.26), P = 0.001; propensity matched cohort: 1.21 (1.01 – 1.35) vs. 1.11 (0.91 – 1.27), p = 0.042, respectively] (Figure 1). Similarly, the degree of PVL was significantly less in the S3 UR group than in the S3 group for both cohorts. In the propensity matched cohort, mild PVL was identified in 6.5% vs. 14.7%, and moderate PVL was present in 0.0% vs. 1.6% (p = 0.028). Peak PG and mean PG were significantly lower in the S3 UR group than in the S3 group for both cohorts. In the propensity matched cohort, peak PG was 17.7 (14.3 – 24.5) vs. 23.2 (18.2 – 29.2) (p = 0.001) and mean PG was 9.0 (7.1 – 12.5) vs. 11.5 (8.9 -14.8) (p = 0.005), respectively. The incidence of PVL ≥ mild, mean PG ≥ 20 mmHg, moderate PPM and severe PPM were tend to be lower in S3 UR group than in the S3 group for both cohorts (Figure 2). Conclusion The S3 UR valve exhibits significant hemodynamic improvements compared to the S3 valve, underscoring its potential for improved clinical outcomes in TAVI patients.

Impact of the underlying rhythm during cavotricuspid isthmus ablation on the incidence of future new-onset atrial fibrillation: insights from an international multi-centre registry

Abstract Background Radiofrequency catheter ablation of the cavotricuspid isthmus (RF-CTI) is the estabslished treatment of typical atrial flutter (AFL). After RF-CTI for AFL patients without previously documented atrial fibrillation (AF) may also develop AF. It is unknown whether the presence or absence of AFL at the time of ablation can predict the future occurence of AF. Purpose To compare baseline characteristics, procedural data, and long-term follow-up (FU) of patients with AFL. Methods Consecutive patients with documented AFL undergoing RF-CTI were enrolled in a multi-center registry in five centers in two countries between February 2017 and July 2023. For patients with AFL, entrainment mapping was performed for confirming CTI dependent AFL. Patients were categorized into two groups, those with AFL and those with sinus rhythm (SR) during RF-CTI. FU data were collected, including clinical assessments, 12-lead electrocardiogram (ECG) and 24-hour Holter-ECGs during each visit. Results Of the 949 subjects, 36% were excluded from the analysis due to a history of AF. A total of 574 patients were included (mean age 68 +/- 11 yrs, 14% females), 62% presented in AFL group and 38 % SR group during CTI. Median FU was 364 days. Patients in AFL group were older (P &amp;lt; 0.029), more likely to have diabetes (P = 0.026), and were less frequently treated with antiarrhythmic drugs (P &amp;lt; 0.001). In the first 12 months of FU, 40% of the patients underwent three FU examinations, while 77% of the patients underwent at least one 24-hour Holter-ECGs during FU. In the Kaplan-Meier analysis patients in AFL group significantly less often developed AF during FU (log-rank, P &amp;lt; 0.016, central ). In the multivariate Cox regression analysis, sinus rhythm during ablation (hazard ratio 1.474; 95% CI 1.043-2.084; P = 0.028), male gender (hazard ratio 1.722; 95% CI 1.116-2.658; P = 0.014) and coronary artery disease (hazard ratio 1.711; 95% CI 1.145-2.555; P = 0.009) were identified as predictors for the occurence of AF during FU. Conclusion Over a one year follow-up, new onset AF occurs significantly less frequently in patients with ongoing atrial flutter during RF-CTI ablation.

Genetic testing in pulmonary hypertension in adults and children

Abstract Pathogenic genetic variants have been found in patients with different forms of pulmonary arterial hypertension (PAH). Our aim was to define the genetic background of patients with idiopathic PAH (IPAH), heritable PAH (HPAH), pulmonary veno-occlusive disease (PVOD) and PAH associated with congenital heart disease (PAH-CHD); both in adult and pediatric age. REHAP and REHIPED are Spanish, voluntary, multicenter registries that include patients with PAH. REHAP started in 2007 and includes patients over 18 years of age. REHIPED started in 2009 and collects patients between 2 months and 18 years of age. Patients with IPAH, HPAH, PVOD and PAH-CHD who have undergone a genetic testing were included. 413 adults and 122 children were analyzed. From 2011, Sanger sequencing and multiplex ligation-dependent probe amplification were used to detect genetic variants in the BMPR2, TBX4, and KCNK3 genes. Since 2014, a next generation sequencing (NGS) panel of 21 genes was applied. In 2017 this panel was expanded to cover 35 genes, and in 2019, it was expanded to 37 genes. Since 2020, whole-exome sequencing has been applied for the previously followed-up patients without known pathogenic/likely pathogenic (P/LP) genetic variants, and for each incident case. There was a statistically significant difference (p 0.031) in the etiologies among adults and children. The etiologies in adults were 242 (59%) IPAH, 25 (6%) HPAH, 83 (20%) PAH-CHD, 63 (15%) PVOD. The etiologies in children were 66 (54%) IPAH, 8 (7%) HPAH, 38 (31%) PAH-CHD, and 10 (8%) PVOD. The genetic testing had a variant in 121 (29%) adults (56% pathogenic, 9% likely pathogenic, 32% VUS) and 63 (52%) children (65% pathogenic, 16% LP, 19% VUS) (adults vs children p &amp;lt; 0.001). BMPR2 was the most frequent variant in both populations, followed by EIF2AK4. Patients with HAPH and PVOD are more likely to have a genetic variant, while PAH-CHD are the less likely to have one; both in adults and children (p&amp;lt;0.001). The etiology was reclassified after the genetic testing in 13% adults and 19% children (p 0.08); including 6 adults and 4 children initially classified as IPAH and then diagnosed of PVOD when a P/LP variant was found in EIF2AK4. Also, 5 children were initially diagnosed as IPAH and then reclassified as multisystemic disorders (4 NFU1 and 1 MECP2) In conclusion, a significant number of patients with PAH have a variant in genetic testing, especially if they are diagnosed in pediatric age. BMPR2 is the most frequent variant in our cohort, followed by EIF2AK4. Knowing the genetic background of our patients enables a better classification and understanding of the disease. This is especially important in patients initially diagnosed of PAHI who are then classified as PVOD. Also, knowing the genetic background may help develop new treatments in the future.

Real world evidence of Sacubitril/Valsartan in octogenarian patients with heart failure. Results From the PARACHUTE-HF Study

Abstract Introduction The beneficial effects of Angiotensin Receptor Neprilysin Inhibitors (ARNI) on heart failure (HF) patients, particularly those with reduced left ventricular ejection fraction (LVEF), have been highlighted in several randomized controlled trials. Since 2020, ARNI has been available for HF treatment in Japan, a country known for its aging population. However, the inclusion of octogenarians in previous trials has been limited, leaving a gap in evidence regarding ARNI's effectiveness in the elderly. Objective This study aims to explore the real-world efficacy and safety of ARNI treatment among octogenarian HF patients in Japan, reflecting its status as a leading aging society. Methods The Prospective Area Registry of ARNI for Congestive Heart failUre in Tokyo East (PARACHUTE) trial, a multicenter registry, was conducted. It involved patients newly prescribed ARNI for chronic HF regardless of LVEF between 2020 and 2021. We compared patient backgrounds, changes in NT-proBNP levels at 6 months, and the rate of ARNI discontinuation between groups aged below and above 80 years. Results The study enrolled 105 patients, with an average age of 75 years. Forty-six patients (44%) were over 80 years old, and the majority (72%) were male. Among the younger group, 50% had preserved LVEF, compared to 32% in the octogenarian group (p=0.01). Median NT-proBNP levels across all patients decreased significantly from 2,540 pg/mL at baseline to 998 pg/mL at 6 months. The reduction in NT-proBNP was similar between the two age groups, with no significant interaction (p=0.46). Discontinuation rates due to any cause were not significantly different between younger and older patients (7% vs. 13%, p=0.28). Conclusion ARNI treatment resulted in significant reductions in NT-proBNP levels in HF patients, both under and over 80 years of age, with comparable discontinuation rates. These findings highlight the effectiveness and safety of ARNI in the management of chronic HF in the elderly, offering valuable real-world evidence from Japan's unique demographic context.

Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after TAVI: insights from an international multicenter registry

Abstract Background The impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI) is controversial. Purpose Our study aims to evaluate the impact of PPM on mortality and clinical-echocardiographic progression of cardiac damage in a "real world" cohort of patients at intermediate and low surgical risk and to characterize its main predictors. Methods 963 patients who underwent TAVI procedure between 2017 and 2021, from an international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations (VARC-3 criteria). Results 18% of patients developed post-TAVI PPM, (7.7% of the whole cohort severe). At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, p=0.33), aged 82y (interquartile range (IQR) 79-85y) vs 82y (IQR 78-86y; p=0.46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, p=0.04); they had smaller left ventricular outflow tract (LVOT) diameter (20mm, IQR 19-21 vs 20mm, IQR 20-22, p=0.02), reduced Stroke Volume index (SVi) (34.2 vs 38 ml/m2, p&amp;lt;0.01) and transaortic flow rate (190.6 vs 211 ml/s, p&amp;lt;0.01). At pre-discharge FU patients with PPM had more paravalvular aortic regurgitation (AR) (moderate/severe AR 15.8% vs 9.2%, p&amp;lt;0.01). At a median FU of 1.46 years (IQR 1-4), there was no evidence of a significant impact of PPM on overall mortality (15.3% vs 13.1%, p=0.46) nor on rehospitalization rate for heart failure (4.3% vs 8.0%, p=0.10). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in endsystolic diameter (ESD) (33 vs 28mm, p=0.03) and a statistically non-significant increase in LV mass index (121 vs 106g/m2, p=0.07). Interestingly, trajectory parameters of patients with PPM from baseline to 1-year FU showed a reduced cardiac remodeling compared to patients without PPM, including no LVEF improvement (p=0.88), absent reduction of LV end-diastolic volume (p=0.70), indexed LV mass (p=0.31), ESD (p=0.48) and pulmonary artery systolic pressure (p=0.82), and an increase of basal RV diameter (p&amp;lt;0.001). Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, p=0.03). Independent predictor of PPM at multivariable logistic regression was male gender (OR=1.93, p=0.04); while SVi (OR=0.86, p&amp;lt;0.001), prosthetic size &amp;gt;23mm (OR=0.62, p=0.03) and LVOT diameter (OR=0.79, p=0.02) had protective effect. Conclusions There was no evidence of a short- or medium-term impact of PPM on mortality. However, clinical-echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations associated with a significant deterioration in NYHA class at 1 year.

Standard modifiable risk factors (SMuRF) paradox for the prognosis in the patients with acute myocardial infarction

Abstract Background Hypertension, diabetes, dyslipidemia and smoking are recognized as standard modifiable risk factors (SMuRFs) for adverse cardiovascular events such as acute myocardial infarction (AMI). Recent studies have shown that AMI patients without SMuRFs are associated with increased mortality compared to those with SMuRFs. However, the relationship between the number of SMuRFs in patients with AMI and mortality has not been well evaluated. Purpose The purpose of this study was to evaluate the clinical characteristics and prognosis of AMI patients stratified by the number of SMuRFs. Methods We studied 6,706 AMI patients between 2013 and 2021 using data from the Mie ACS registry, a retrospective and multicenter registry. For the purpose of this study, only AMI patients as their first cardiovascular events were included in this analysis. Therefore, after excluding patients with a known history of coronary artery disease (n=982), 5724 AMI patients were included in the current analysis. All-cause mortality was compared with 30-day and after 30-day mortality in AMI patients stratified by the number of SMuRFs as the primary outcome. In addition, all-cause mortality rate was compared in AMI patients without and with SMuRFs after propensity score matching on age, sex, body mass index, Killip classification, cardiac arrest before presentation, multivessel disease, left main truck disease, hemoglobin and emergent percutaneous coronary intervention. Results Among 5,724 AMI patients, 672 patients (11.7%) did not have SMuRFs. The median age of patients without SMuRFs was higher than that of patients with any SMuRFs (73 y.o. vs. 70 y.o, P&amp;lt;0.001), and higher prevalence of female and severe Killip class was observed in patients without SMuRFs compared with those with any SMuRFs (P&amp;lt;0.001, respectively). According to the KM survival curves stratified by number of SMURFs, an increased number of SMURFs was associated with higher 30-day survival rates (P=0.035), and the 30-day landmark analysis showed a trend toward higher survival in patients with the highest number of SMURFs, although not statistically significant (Figure1). Multivariate Cox regression analysis showed that 0 SMuRF was an independent prognostic factor for 30-day mortality with hazard ratio of 1.55 (95%CI; 1.13-2.13, P&amp;lt;0.001). In addition, KM survival curves after propensity score matched analysis showed the poor 30-day mortality in 0 SMuRF group (P=0.036), there was no significant difference in after 30-day mortality between the two groups (Figure 2). Conclusions Patients without SMuRFs had a high 30-day mortality rate, but once they survived the acute phase, their prognosis was comparable to patients with SMuRFs. Moreover, the SMuRF paradox was recognized in the acute phase. This finding highlights the need for early identification of the individuals at risk of developing MI despite the absence of SMuRFs and strict acute management regardless of the number of SMuRFs.

Symptom assessment and angina classification of patients with ischemia and nonobstructive coronary arteries undergoing invasive coronary function testing: from the DISCOVER INOCA multicenter registry

Abstract Background Patients with ischemia and nonobstructive coronary arteries (INOCA) suffer from a broad range of anginal symptoms that may differ depending on the biologic sex of the patient, the underlying coronary vasomotor disorder, or the type of presentation. Purpose We sought to characterize the symptom description and angina classification of patients referred for invasive coronary function testing (CFT) in the DISCOVER INOCA multicenter registry, stratified by type of presentation (stable vs unstable), biologic sex, and underlying diagnosis, including coronary microvascular dysfunction (CMD), vasospastic angina (VSA), or other disorders such as symptomatic myocardial bridging. Methods DISCOVER INOCA is a prospective, multicenter registry in the United States that includes patients who are referred for clinically indicated coronary angiography and found to have INOCA. All patients underwent protocol-guided angiography, acetylcholine provocation, coronary thermodilution, and intravascular imaging. Symptom characteristics were compared between groups. Results From September 2022 until February 2024, 104 patients were enrolled, 78% were female, and mean age was 57 ± 11 years. The post-procedure diagnosis was CMD in 19%, VSA in 41%, a mixed syndrome in 15%, or other diagnosis in 26%. The average coronary flow reserve (CFR) was 2.9 ± 1.1 in the CMD group and 5.3 ± 3.0 in the VSA group, (p &amp;lt; 0.001). 53% of patients presented with stable angina and 47% with unstable or progressive symptoms. Symptoms included chest pain (89%), chest tightness (42%), chest pressure (39%), shortness of breath (53%), and fatigue (16%), and no significant differences were reported when stratified by diagnostic phenotype. Female patients were more likely to report arm/neck/back/jaw pain (25% vs 5% in men, p = 0.038). Symptom triggers included exertion/activity in 73%, emotional stress in 12%, and resting symptoms in 58%. In female patients 4% reported catamenial symptoms. Of patients with stable angina, the Canadian Cardiovascular Society (CCS) Angina Classification was Grade I in 25%, Grade II in 52%, Grade III in 21%, and Grade IV in 2%. In patients with unstable angina, the Braunwald Angina Classification was Class I in 9%, Class II in 73%, and Class III in 18%. Conclusions Patients with INOCA referred for clinically indicated coronary angiography and CFT were predominantly female and most commonly reported chest pain as a presenting symptom. Female patients were more likely to report arm/neck/back/jaw pain than male patients. Over half of patients reported resting symptoms with no differences between the diagnostic phenotypes (CMD, VSA, or other). The CCS and Braunwald angina classification indicated that most patients had moderate intensity symptoms. Patient-reported outcome measures will be used to systematically categorize the symptom burden in these patients.

Clinical characteristics and predictors of recurrence from the Australia-New Zealand Spontaneous Coronary Artery Dissection (ANZ-SCAD) registry

Abstract Background Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute coronary syndrome (ACS), particularly in young women. Our understanding of SCAD remains incomplete with limited prospective data on determinants of SCAD recurrence. Purpose We aimed to describe the clinical characteristics, incidence and predictors of SCAD recurrence and major adverse cardiovascular events (MACE) in patients with SCAD from a large, multicentre registry. Methods Observational, multi-centre prospective and retrospective cohort study recruiting patients with SCAD from 23 hospitals in Australia and New Zealand. Patients aged=&amp;gt;18 years with SCAD and an ACS were eligible for inclusion. Prospectively recruited patients gave their informed consent while a waiver of consent was granted for retrospectively recruited patients. An independent core laboratory adjudicated invasive coronary angiography images to confirm the diagnosis of SCAD. The primary outcome was SCAD recurrence, defined as de novo spontaneous dissection with new ACS symptoms and cardiac enzyme elevation, not due to extension of the index lesion. Cox proportional hazard models were used to evaluate the association between SCAD recurrence and predefined clinical variables. Results From a total 487 patients recruited, 423 (132 prospective and 291 retrospective) patients with SCAD confirmed on core laboratory review were included for analysis. Mean age was 52.4±10.7 years, 89.7% were female and 73.1% were Caucasian. At discharge, 75.2% were on beta-blockers, 27.9% single antiplatelet and 61.9% dual antiplatelet (DAPT). At 15 (interquartile range 5-36) months median follow-up, SCAD recurrence occurred in 3.3%, with an overall MACE of 6.6%. On multivariate analysis, the presence of fibromuscular dysplasia (FMD) or other extra-cardiac vascular abnormalities [adjusted hazard ratio (HR) 5.63, 95% confidence interval (CI), 2.09-15.3, p&amp;lt;0.001], and past history of stroke (adjusted HR 7.99, 95% CI, 1.51-42.4, p=0.015) were associated with higher SCAD recurrence. Discharge beta-blockers was not independently associated with SCAD recurrence, while dual antiplatelet therapy that combined ticagrelor with aspirin was associated with a higher risk of recurrence (adjusted HR 2.47, 95% CI, 1.9-15.6, p=0.048). Conclusion SCAD recurrence comprised half of overall MACE in people with SCAD. The risk of SCAD recurrence was more than 5-fold higher in patients with FMD or other extra-cardiac vascular abnormalities. Dual-antiplatelet therapy that comprised ticagrelor and aspirin was associated with a higher risk of SCAD recurrence.

Effects of beta blockers on outcome in patients with PAH with and without comorbid conditions: a Multicenter Prospective Cohort Study (BNP-PL)

Abstract Background The current guidelines do not recommend the use of beta-blockers (BB) in patients with pulmonary arterial hypertension (PAH) unless necessitated by comorbidities. However, the evidence regarding the role of BB in PAH is contradictory. This study investigates the effects of BB on clinical outcomes in patients newly diagnosed with PAH, stratified by the presence of cardiovascular comorbidities that justify their use. Methods We analyzed data from 806 patients newly diagnosed with PAH, who were prospectively enrolled from March 1, 2018, to August 31, 2023, in the multicentre registry, Database of Pulmonary Hypertension in the Polish population (BNP-PL). The primary endpoints were all-cause mortality and a composite of hospitalization due to right heart exacerbation, syncope, or death. The follow-up period for these patients extended until August 31, 2023. Comorbidities in the study group that indicated the need for BB therapy included hypertension, significant arrhythmia, and coronary artery disease. In the Cox regression analysis, the association between BB use and the predefined endpoints was adjusted for age, baseline European Society of Cardiology risk score, and upfront therapy. Results Among the 806 patients, BBs were administered to 469 (58.2%) at the time of PAH diagnosis. In the entire cohort, BB therapy was linked to increased all-cause mortality (29.6% vs 21.4%; p=0.005, Fig 1.A) and a higher incidence of the composite endpoint (34.1% vs 22.6%; p&amp;lt;0.0001, Fig 1.B). The Number Needed to Harm (NNH) for BB treatment, regarding mortality and the composite endpoint, were 12.1 and 8.7, respectively. In patients without comorbidities, BB use significantly raised the risk of both all-cause mortality (Hazard Ratio [HR] 1.81, 95% Confidence Interval [CI]: 1.01-3.15) and the composite endpoint (HR 1.85, 95% CI 1.09-3.14), after adjustments for age, baseline three-strata PAH mortality risk, and upfront therapy. However, in patients with at least one comorbidity, BB therapy showed a neutral effect on both outcomes. Across the whole group, the use of nonselective BB was associated with a higher risk of the composite endpoint (HR 1.78, 95% CI 1.13-2.82, p=0.01) compared to selective β1 agents, although this did not extend to all-cause mortality (HR 1.34, 95% CI 0.79-2.25, p=0.28). Conclusion BBs, particularly nonselective, pose significant risks in patients with PAH who lack comorbidities that justify their use.

Clinical phenotyping and treatment response in patients with chronic heart failure: a latent class analysis from a Japanese multicentre registry

Abstract Background There are diversities of pathophysiology and co-morbidities in patients with chronic heart failure (HF), irrespective of left ventricular ejection fraction (LVEF). Therefore, the identification of subgroups with different outcomes and treatment response patterns may help to tailor strategies to each individual HF patient. Purpose We sought to identify phenogroups of patients with different prognosis and response to medical therapies in patients with chronic HF. Methods A total of 1565 patients with a broad spectrum of LVEF in a prospective multicentre registry of patients with chronic HF were enrolled between January 2020 and December 2023. Latent class analysis was performed in each subgroup using 80 features including patients’ demographics, laboratory, and echocardiographic data. The optimal number of phenogroups was determined using the first minimum of the Bayesian information criterion. The primary outcome was a composite of all-cause death and hospitalisation due to worsening HF. Results The analysis subclassified patients into six phenogroups. Patients in phenogroup A (young non-ischaemic cardiomyopathy, n = 242, 15.5%) were the youngest and had lower LVEF and lowest prevalence of coronary artery disease (CAD) and other comorbidities. Phenogroup B (atrial fibrillation [AF] and small left atrium, n = 282, 18.0%) had higher proportion of AF but smaller left atrium volume. Phenogroup C (ischaemic cardiomyopathy, n = 204, 13.0%) had the highest proportion of CAD and lower LVEF. Phenogroup D (classical HF with preserved ejection fraction [HFpEF], n =308, 19.7%) had the highest age, proportion of female, LVEF and thickness of LV wall. Phenogroup E (elderly and AF , n = 235, 15.0%) had higher age, the highest proportion of AF and largest left atrium volume. Phenogroup F (biventricular failure and multiple comorbidities, n = 294, 18.8%) had the highest proportion of co-morbidities and the lowest LVEF, right ventricular systolic function and renal function. During a median follow-up period of 538 (interquartile range 286-701) days, the incidence of the primary outcome significantly differed among the phenogroups (P &amp;lt; 0.001, Figure 1). Regarding treatment response for renin-angiotensin system blockers and beta blockers, there were no significant associations between the use of renin-angiotensin system blockers and the risk of the primary outcome among the phenogroups whereas the use of beta-blockers was significantly associated with increased risk of the primary outcome in patients classified to phenogroup D (classical HFpEF) (hazard ratio 1.83 95% confidence interval 1.05-3.19) among the phenogroups (Figure 2). Conclusion We identified six phenogroups with distinct clinical outcomes in patients with chronic HF, and the use of beta-blockers might have unfavorable effect in the classical HFpEF phenogroup. This phenotyping provides novel risk stratification and may aid in clinical decision making.Clinical outcomes among the phenogroupsTreatment effect among the phenogroups

Prognostic value of reticulocyte production ability in patients with chronic heart failure

Abstract Background Anaemia is frequently observed in patients with chronic heart failure (CHF), and many studies have elucidated the association between anaemia and mortality in patients with CHF. The quality of erythropoiesis is an intrinsic aspect of pathophysiology of anaemia, and the ability of reticulocyte production would be one of the pivotal factors in the quality of erythropoiesis. Purpose We sought to investigate whether the reticulocyte production ability is associated with clinical outcomes, and clarify the pathophysiology of reticulocyte production in patients with CHF. Methods We prospectively examined 1,328 symptomatic CHF patients (median age 71 [IQR 65-82] years, mean left ventricular ejection fraction 50 ± 16%, median NT-proBNP 743 [IQR 360–1710] pg/mL) in a multicentre registry with 27 Japanese sites between January 2020 and October 2023. The reticulocyte production ability was evaluated by calculating the reticulocyte production index (RPI) using reticulocyte counts and serum haematocrits. Patients were divided into four groups according to the presence or absence of WHO defined anaemia and the median value of RPI. The primary outcome was a composite of all-cause death and hospitalisation for worsening HF. Results During a median follow-up period of 551 (IQR 321–712) days, the primary outcome occurred in 219 (17%) patients. The group with anaemia and high RPI (≥0.978, the median) showed the highest incidence of the primary outcome among the groups (P &amp;lt; 0.001) (Figure 1). Multivariable regressions showed that higher RPI was independently associated with the higher risk of the primary outcome, even after adjustment for NT-proBNP, sodium, haemoglobin, serum iron, erythropoietin, and MAGGIC risk score (HR 1.41, 95% CI 1.09–1.82). Erythrocyte counts were significantly increased in patients with higher RPI compared to those with lower RPI in the groups without anaemia (P &amp;lt; 0.001)whereas there were no significant differences on erythrocyte counts between the groups with anaemia (P = 0.90) (Figure 2A). Patients with higher RPI had higher log erythropoietin levels compared to those with lower RPI in either anaemic or non-anaemic group (Figure 2B). In addition, serum iron levels and transferrin saturation did not significantly differ between the RPI groups in either anaemic or non-anaemic group (Figures 2C and D). Furthermore, in patients without anaemia, erythrocyte counts positively correlated with RPI (R = 0.27, P &amp;lt; 0.001) whereas there was very weak correlation between erythrocyte counts and RPI in those with anaemia (R = 0.07, P = 0.045). Conclusions Higher RPI was independently associated with worse clinical outcomes, suggesting RPI could be a surrogate marker for risk stratification in patients with CHF, especially in anaemic population. Higher reticulocyte production ability might reflect the impaired maturation of reticulocytes to erythrocytes independent of iron parameters.

Prognostic value of albumin-bilirubin score in patients with chronic heart failure

Abstract Background Liver dysfunction is one of the common comorbidities, and associated with worse clinical outcomes in patients with chronic heart failure (CHF). Recently, the albumin-bilirubin (ALBI) score has been developed as an effective and convenient scoring system for assessing liver function. However, the prognostic significance of the ALBI score in patients with CHF remained to be clarified. Purpose We sought to investigate the clinical significance of ALBI score on outcome prediction in patients with CHF. Methods We prospectively examined 1567 symptomatic CHF patients (median age 74, inter quartile range [IQR] 64-82 years, mean left ventricular ejection fraction [LVEF] 49 ± 15.9 %, median N-terminal pro-brain natriuretic peptide [NT-pro BNP] 801 [IQR 372-1820] pg/ml) in a multicentre registry with 27 Japanese sites between January 2020 and December 2023. The ALBI score was calculated according to the following formula: log10 total bilirubin (mg/dl) × 0.06 + albumin (g/dL) × 10 × (-0.085). Studied patients were divided into three groups according to the ALBI grade; ALBI score ≤ -2.60 (Grade1, n = 691), -2.60 &amp;lt; ALBI score ≤ -1.39 (Grade 2, n = 864), ALBI score &amp;gt; -1.39 (Grade3, n = 12). Primary outcome of interest was a composite of all-cause death and hospitalisation due to worsening heart failure. Results Patient with higher ALBI grade had higher age, New York Heart Association functional class, NT-pro BNP level, prevalence of atrial fibrillation and chronic obstructive pulmonary disease, and lower body mass index, systolic blood pressure, haemoglobin level, serum albumin level and estimated glomerular filtration rate compared to those with lower ALBI grade. LVEF was comparable between the groups. During a median follow-up period of 537 (IQR 285-701) days, the primary outcome occurred in 267 patients (17%). Higher ALBI grade were significantly related to increased incidence of the primary outcome (P for trend &amp;lt; 0.001) (Figure 1). Multivariable Cox regressions showed that a higher ALBI score was independently associated with higher risk of the primary outcome (hazard ratio 2.8, 95% confidential interval (CI) 2.08-3.77, P &amp;lt; 0.001), even after adjustment for the MAGGIC score as an established risk prediction model, NT-pro BNP, aspartate aminotransferase, and platelet counts. Furthermore, addition of the ALBI score to the MAGGIC score significantly increased c-index from 0.70 (95% CI 0.66-0.74) to 0.73 (95% CI 0.69-0.76) (P &amp;lt; 0.001) (Figure 2). The net reclassification improvement afforded by the ALBI score was 26% for the primary outcome (P&amp;lt;0.001). Conclusions Liver dysfunction assessed by the ALBI score was independently associated with worse clinical outcomes in patients with CHF. Moreover, addition of the score to the existing risk prediction model significantly increased the ability of outcome prediction, suggesting beneficial clinical application of the ALBI score in patients with CHF.

Is etiology of severe tricuspid regurgitation related to prognosis?

Abstract Objective Our aim was to assess the prognostic role of the etiology tricuspid valve disease in patients with severe tricuspid regurgitation (TR). Methods Multicenter, observational, and prospective registry in which all patients with severe TR have been consecutively collected within a 6-month period and followed up for one year. Results A total of 1247 patients with severe TR [mean age: 76.7±10.5 years, 876 women (70.2%)] were included: 810 (64.9%) met criteria for severe TR, 301 (24.1%) massive TR, and 136 (11%) torrential TR. The most frequent etiology was functional TR secondary to left-heart disease in 621 patients (49.9%) followed by "atriogenic" TR in 247 (19.8%). TR etiology distribution is described in Figure 1. Death due to refractory HF occurred in 9,2% of patients, hospitalization for HF in 20,8%, and 12,3% underwent TR interventions. In the univariate and multivariate analysis, age, impaired renal function, previous HF admission, and massive and torrential TR were associated with an increased risk of HF hospitalization and cardiovascular mortality. Global (p=0,476) and cardiovascular mortality (p=0,138) rates were similar when comparing different TR etiologies (Figure 2). Conclusion Severe TR is associated with high rates of CV mortality and new HF admission. These findings are and independent from TR etiology.

A new right-heart failure staging system in patients with severe tricuspid regurgitation. Prognostic implications

Abstract Objective Our aim was to describe a new right-heart failure (RHF) staging system in patients with severe tricuspid regurgitation (TR). Methods Multicenter, observational, and prospective registry in which all patients with severe TR have been consecutively collected within a 6-month period, classified according to their clinical condition and right ventricular status, and followed up for one year. Results A total of 1247 patients with severe TR [mean age: 76.7±10.5 years, 876 women (70.2%)] were included: 810 (64.9%) met criteria for severe TR, 301 (24.1%) massive TR, and 136 (11%) torrential TR. A new RHF staging was proposed depending on clinical condition, RV dilation and RV systolic dysfunction (Table). The largest group of patients had a normal right ventricle with signs/symptoms of RHF (41%). Death due to refractory HF occurred in 9,2% of patients, hospitalization for HF in 20,8%, and 12,3% underwent TR interventions. In the multivariate analysis the predictors of CV mortality were age, impaired renal function, previous HF admission, massive and torrential TR and Stages III and IV of the new right-heart failure staging system (figure). Conclusion The new RHF staging system accurately stratifies patients with severe TR into prognostic categories.

Overview of the risk of myocardial infarction in patients with aortic stenosis: insights from the VALVENOR Registry

Abstract Background Close interaction between aortic stenosis (AS) and coronary artery disease (CAD) has been suggested. However, the risk of myocardial infarction (MI) in patients with AS is poorly described outside the context of aortic valve replacement. Objectives To assess the incidence, correlates and impact on outcomes of MI occurrence in patients with different degrees of AS severity. Methods Between 2016 and 2017, the multicenter prospective VALVENOR registry enrolled 2,830 outpatients with native valvular AS (peak aortic jet velocity (Vmax) ≥ 2.5m/s). AS was defined as mild (Vmax 2.5-2.9), moderate (Vmax 3-3.9) or severe (Vmax ≥4). MI was defined using the 4th universal definition (type 2 MI were not considered). Results The mean age was 76.0 years, 54% of the patients were men and 18.3% had experienced prior coronary event (PCE). Altogether, one third (n=820 [30.3%]) of the patients had diabetes. At 5 years, the cumulative incidence of MI (death as competing event) was only 2.5% (n=72, 1/3 of ST-elevation MI). Sixty MI (83.3%) were categorized as type 1 MI while 12 were peri-procedural MI (surgical aortic valve replacement, n=5; transcatheter aortic valve replacement, n=2; coronary artery bypass surgery, n=1; percutaneous coronary intervention, n=3; coronary angiography, n=1). PCE and angina symptoms were associated with an increased risk, whereas female gender with a decreased risk. By contrast, AS severity was not associated with the risk of MI. Five-year cumulative incidence of MI was 6.5% [95% CI, 4.5 - 8.9] in patients with PCE vs. 1.7% [95% CI, 1.2 - 2.3] in patients with no PCE (P&amp;lt;0.001), 8.3% [95% CI, 4.1 - 14.4] in patients with angina vs. 2.3% [95% CI, 1.8 - 2.9] in patients without angina (P&amp;lt;0.001), and 3.2% [95% CI, 2.4 - 4.2] in men vs. 1.8% [95% CI, 1.1 - 2.6] in women (P=0.014). Subsequent mortality was high and at 52.8% during follow-up (median 648 days after MI occurrence). When analyzed as a time-dependent variable, incident MI was a powerful predictor of mortality (HR=2.00, P&amp;lt;0.001 after adjustment). Conclusions In patients with AS, the risk of MI is relatively low especially in patients without PCE and without angina. No association between the risk of MI and AS severity was observed. Although rare, incident MI is strongly associated with subsequent mortality.