Coronary Microvascular Dysfunction in Patients With Heart Failure: Characterization of Patterns in HFrEF Versus HFpEF.

BACKGROUND: Coronary microvascular dysfunction (CMD) is involved in heart failure (HF) onset and progression, independently of HF phenotype and obstructive coronary artery disease. Invasive assessment of CMD might provide insights into phenotyping and prognosis of patients with HF. We aimed to assess absolute coronary flow, absolute microvascular resistance, myocardial perfusion, coronary flow reserve, and microvascular resistance reserve in patients with HF with preserved ejection fraction and HF with reduced ejection fraction (HFrEF). METHODS: Single-center, prospective study of 56 consecutive patients with de novo HF with nonobstructive coronary artery disease divided into HF with preserved ejection fraction (n=21) and HFrEF (n=35). CMD was invasively assessed by continuous intracoronary thermodilution and defined as coronary flow reserve <2.5. Left ventricular and left anterior descending artery-related myocardial mass was quantified by echocardiography and coronary computed tomography angiography. Myocardial perfusion (mL/min per g) was calculated as the ratio between absolute coronary flow and left anterior descending artery-related mass. RESULTS: Patients with HFrEF showed a higher left ventricular and left anterior descending artery-related myocardial mass compared with HF with preserved ejection fraction (P<0.010). Overall, 52% of the study population had CMD, with a similar prevalence between the 2 groups. In HFrEF, CMD was characterized by lower absolute microvascular resistance and higher absolute coronary flow at rest (functional CMD; P=0.002). CMD was an independent predictor of a lower rate of left ventricular reverse remodeling at follow-up. In patients with HF with preserved ejection fraction, CMD was mainly due to higher absolute microvascular resistance and lower absolute coronary flow during hyperemia (structural CMD; P≤0.030). CONCLUSIONS: Continuous intracoronary thermodilution allows the definition and characterization of patterns with distinct CMD in patients with HF and could identify patients with HFrEF with a higher rate of left ventricular reverse remodeling at follow-up.

Validation of an automated artificial intelligence system for 12­lead ECG interpretation.

BACKGROUND: The electrocardiogram (ECG) is one of the most accessible and comprehensive diagnostic tools used to assess cardiac patients at the first point of contact. Despite advances in computerized interpretation of the electrocardiogram (CIE), its accuracy remains inferior to physicians. This study evaluated the diagnostic performance of an artificial intelligence (AI)-powered ECG system and compared its performance to current state-of-the-art CIE. METHODS: An AI-powered system consisting of 6 deep neural networks (DNN) was trained on standard 12­lead ECGs to detect 20 essential diagnostic patterns (grouped into 6 categories: rhythm, acute coronary syndrome (ACS), conduction abnormalities, ectopy, chamber enlargement and axis). An independent test set of ECGs with diagnostic consensus of two expert cardiologists was used as a reference standard. AI system performance was compared to current state-of-the-art CIE. The key metrics used to compare performances were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score. RESULTS: A total of 932,711 standard 12­lead ECGs from 173,949 patients were used for AI system development. The independent test set pooled 11,932 annotated ECG labels. In all 6 diagnostic categories, the DNNs achieved high F1 scores: Rhythm 0.957, ACS 0.925, Conduction abnormalities 0.893, Ectopy 0.966, Chamber enlargement 0.972, and Axis 0.897. The diagnostic performance of DNNs surpassed state-of-the-art CIE for the 13 out of 20 essential diagnostic patterns and was non-inferior for the remaining individual diagnoses. CONCLUSIONS: Our results demonstrate the AI-powered ECG model's ability to accurately identify electrocardiographic abnormalities from the 12­lead ECG, highlighting its potential as a clinical tool for healthcare professionals.

High efficiency single-catheter workflow for radiofrequency atrial fibrillation ablation in the QDOT catheter era.

BACKGROUND: High-power short-duration (HPSD) ablation may improve the consistency and efficiency of pulmonary vein isolation (PVI). The novel QDOT Micro™ catheter (Biosense Webster, Inc.) with temperature feedback and microelectrodes aims to enhance PVI efficiency and safety. This study wants to evaluate the feasibility, safety, and efficiency of a standardized single-catheter workflow for PVI using QDOT (Q-FLOW). METHODS: The Q-FLOW includes single transeptal access, radiofrequency encircling of the PVs using a power of 50 W in a temperature/flow-controlled mode, and validation of the circles with microelectrodes. A 1:1 propensity-matched cohort of patients treated with conventional power-controlled ablation using a circular mapping catheter (CMC-FLOW) was used to compare procedural and clinical outcomes. RESULTS: A total of 150 consecutive atrial fibrillation patients (paroxysmal 67%, persistent 33%) were included. First-pass isolation rate was 86%. Procedural time, X-ray time, and dose were significantly lower for the Q-FLOW vs the CMC-FLOW (67.2 ± 17.9 vs 88.3 ± 19.2 min, P < 0.001; 3.0 ± 1.9 vs 5.0 ± 2.4 min, P < 0.001; 4.3 ± 1.9 vs 6.4 ± 2.3 Gycm2, P < 0.001). Complications were numerically but not significantly lower in the Q-FLOW group (2 [1.3%] vs 7 [4.7%], P = 0.091). There was no difference in arrhythmia recurrence at 12 months (atrial arrhythmia-free survival rate, 87.5% vs 84.4%, P = 0.565). CONCLUSION: A streamlined single-catheter workflow for PVI using QDOT was feasible and safe, resulting in a high rate of first-pass isolation and a low complication rate. The Q-FLOW further improved the efficiency of PVI compared to the standard CMC-FLOW, without difference in the 12-month outcome.

Association of Mild-to-Moderate Aortic Regurgitation With Outcomes in Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: To assess aortic regurgitation (AR) prevalence, its hemodynamic effect, and long-term prognostic implications in patients admitted with de novo or worsened heart failure with preserved ejection fraction (HFpEF). METHODS: Consecutive patients hospitalized with de novo or worsened HFpEF between 2014 and 2020 were enrolled. Patients with more than moderate aortic and/or mitral valve disease were excluded. Based on the presence and degree of AR, patients were divided into those without AR, those with mild, and those with moderate AR. Data on cardiovascular death, heart failure (HF) rehospitalization, and their composite (major adverse cardiovascular events) were collected. RESULTS: The final study population consisted of 458 HFpEF patients: 156 (34.1%) with mild-AR, 153 (33.4%) with moderate-AR, and the remaining 149 (32.5%) with no AR. Mild-to-moderate AR patients were older, with larger left atrium-left ventricle (LV) volumes, greater LV mass index, higher filling pressure, and prevalence of diastolic dysfunction compared with the no-AR group (all P<.05). During 5-year follow-up, 113 patients died of cardiovascular causes, 124 patients were rehospitalized for HF, whereas 196 experienced the composite endpoint. Mild-to-moderate AR was identified as an independent predictor of all-cause death (HR, 1.62; 95% CI, 1.14 to 1.58; P=.04) and major adverse cardiovascular event occurrence (HR, 1.48; 95% CI, 1.05 to 2.09; P=.02). A total of 126 (35.5%) of 355 patients showed progression of AR at follow-up echocardiography. CONCLUSION: Mild-to-moderate AR is common among patients hospitalized for HFpEF. It is associated with adverse LV remodeling and worse long-term outcomes. These findings warrant further prospective studies addressing the importance of AR in prognostic stratification and exploring therapeutic strategies to mitigate its hemodynamic effect on HF.

Innovative Device-Based Strategies for Managing Acute Decompensated Heart Failure.

Acute decompensated heart failure (ADHF) is a major cause of hospitalizations in older adults, leading to high mortality, morbidity, and healthcare costs. To address the persistent poor outcomes in ADHF, novel device-based approaches targeting specific pathophysiological mechanisms are urgently needed. The recently introduced DRI2P2S classification categorizes these innovative therapies based on their mechanisms. Devices include dilators (increasing venous capacitance), removers (directly removing sodium and water), inotropes (enhancing left ventricular contractility), interstitials (accelerating lymph removal), pushers (increasing renal arterial pressure), pullers (decreasing renal venous pressure), and selective drippers (selective intrarenal drug infusion). Some are tailored for chronic HF, while others focus on the acute setting. Most devices are in early development, necessitating further research to understand mechanisms, assess clinical effectiveness, and ensure safety before routine use in ADHF management. Exploring these innovative device-based strategies may lead to improved outcomes and revolutionize HF treatment in the future.

Pre-cath Laboratory Planning for Left Atrial Appendage Occlusion - Optional or Essential?

In the wake of rapid advancement in cardiovascular procedural technologies, physician-led preprocedural planning utilizing multi-modality imaging training is increasingly recognized as invaluable for procedural accuracy. Left atrial appendage occlusion (LAAO) is one such procedure in which complications such as device leak, cardiac injury, and device embolization can be decreased substantially with incorporation of physician driven imaging and digital tools. We discuss the benefits of cardiac CT and 3D printing in preprocedural planning for the Heart Team, as well as novel applications by physicians of intraprocedural 3D angiography and dynamic fusion imaging. Furthermore, incorporation of computational modeling and artificial intelligence (AI) may yield promise. For optimal patient-centric procedural success, we advocate for standardized preprocedural imaging planning by physicians within the Heart Team as an essential part of LAAO.

Diagnostic and Prognostic Role of Cardiac Magnetic Resonance in MINOCA: Systematic Review and Meta-Analysis.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is common in current clinical practice. Cardiac magnetic resonance (CMR) plays an important role in its management and is increasingly recommended by all the current guidelines. However, the prognostic value of CMR in patients with MINOCA is still undetermined. OBJECTIVES: The purpose of this study was to determine the diagnostic and prognostic value of CMR in the management of patients with MINOCA. METHODS: A systematic review was performed to identify studies reporting the results of CMR findings in patients with MINOCA. Random effects models were used to determine the prevalence of different disease entities: myocarditis, myocardial infarction (MI), or takotsubo syndrome. Pooled odds ratios (ORs) and 95% CIs were calculated to evaluate the prognostic value of CMR diagnosis in the subgroup of studies that reported clinical outcomes. RESULTS: A total of 26 studies comprising 3,624 patients were included. The mean age was 54.2 ± 5.3 years, and 56% were men. MINOCA was confirmed in only 22% (95% CI: 0.17-0.26) of the cases and 68% of patients with initial MINOCA were reclassified after the CMR assessment. The pooled prevalence of myocarditis was 31% (95% CI: 0.25-0.39), and takotsubo syndrome 10% (95% CI: 0.06-0.12). In a subgroup analysis of 5 studies (770 patients) that reported clinical outcomes, CMR diagnosis of confirmed MI was associated with an increased risk of major adverse cardiovascular events (pooled OR: 2.40; 95% CI: 1.60-3.59). CONCLUSIONS: In patients with MINOCA, CMR has been demonstrated to add an important diagnostic and prognostic value, proving to be crucial for the diagnosis of this condition. Sixty-eight percent of patients with initial MINOCA were reclassified after the CMR evaluation. CMR-confirmed diagnosis of MINOCA was associated with an increased risk of major adverse cardiovascular events at follow-up.

Ambulatory pulmonary vein isolation workflow using the Perclose ProglideTM suture-mediated vascular closure device: the PRO-PVI study.

AIMS: The leading reason for delayed discharge after pulmonary vein isolation (PVI) is vascular complications. This study aimed to evaluate feasibility, safety, and efficacy of the Perclose Proglide™ suture-mediated vascular closure in ambulatory PVI, report complications, patient satisfaction, and cost of this approach. METHODS AND RESULTS: Patients scheduled for PVI were enrolled prospectively in an observational design. Feasibility was assessed as % discharged the day of procedure. Efficacy was analysed as acute access site closure rate, time to reach haemostasis, time to ambulate, and time to discharge. Safety analysis consisted of vascular complications at 30 days. Cost analysis was reported using direct and indirect cost analysis. A 1:1 propensity matched control cohort was used for comparing time to discharge to usual workflow. Of 50 enrolled patients, 96% were discharged on the same day. 100% of devices were successfully deployed. Immediate (<1 min) haemostasis was reached in 30 patients (62.5%). Mean time to discharge was 5:48 ± 1:03 h (vs. 10:16 ± 1:21 h in the matched cohort, P < 0.0001). Patients reported high level of satisfaction with the post-operative time. No major vascular complication occurred. Cost analysis showed a neutral impact compared to the standard of care. CONCLUSION: The use of the closure device for femoral venous access after PVI led to safe discharge of patients within 6 h from the intervention in 96% of the population. This approach could minimize the overcrowding of healthcare facilities. The gain in post-operative recovery time improved patients' satisfaction and balanced the economic cost of the device.

Risk factors for Gram-negative bacterial infection of cardiovascular implantable electronic devices: multicentre observational study (CarDINe Study).

BACKGROUND: Infections of cardiovascular implantable electronic devices (CIED) are mainly due to Gram-positive bacteria (GPB). Data about Gram-negative bacteria CIED (GNB-CIED) infections are limited. This study aimed to investigate risk factors, clinical and diagnostic characteristics, and outcome of patients with GNB-CIED. METHODS: A multicentre, international, retrospective, case-control-control study was performed on patients undergoing CIED implantation from 2015 to 2019 in 17 centres across Europe. For each patient diagnosed with GNB-CIED, one matching control with GPB-CIED infection and two matching controls without infection were selected. RESULTS: A total of 236 patients were enrolled: 59 with GNB-CIED infection, 59 with GPB-CIED infection and 118 without infection. No between-group differences were found regarding clinical presentation, diagnostic and therapeutic management. A trend toward a higher rate of fluorodeoxyglucose positron emission computed tomography (FDG PET/CT) positivity was observed among patients with GNB than in those with GPB-CIED infection (85.7% vs. 66.7%; P = 0.208). Risk factors for GNB-CIED infection were Charlson Comorbidity Index Score (relative risk reduction, RRR = 1.211; P = 0.011), obesity (RRR = 5.122; P = 0.008), ventricular-pacing ventricular-sensing inhibited-response pacemaker implantation (RRR = 3.027; P = 0.006) and right subclavian vein site of implantation (RRR = 5.014; P = 0.004). At 180-day survival analysis, GNB-CIED infection was associated with increased mortality risk (HR = 1.842; P = 0.067). CONCLUSIONS: Obesity, high number of comorbidities and right subclavian vein implantation site were associated with increased risk of GNB-CIED infection. A prompt therapeutic intervention that may be guided using FDG PET/CT is suggested in patients with GNB-CIED infection, considering the poorer outcome observed in this group.

Safety of Right and Left Ventricular Endomyocardial Biopsy in Heart Transplantation and Cardiomyopathy Patients.

BACKGROUND: Endomyocardial biopsy (EMB) facilitates a histopathologic diagnosis with unique prognostic and therapeutic implications in both native and donor hearts. It is a relatively safe procedure, with an overall complication rate ranging from <1% to 6% depending on the experience of the operator, the clinical status of the patient, the presence or absence of left bundle branch block, the access site, and the site of procurement (right ventricular [RV] vs left ventricular [LV] approach). OBJECTIVES: This study aimed to assess the incidence of procedure-related complications in a real-world population. EMBs were performed either for surveillance of rejection episodes after heart transplantation or for diagnosis of etiology of cardiomyopathy. METHODS: The authors retrospectively analyzed 1,368 biopsies obtained in 561 consecutive patients between May 2011 and May 2021. Patients were stratified according to the underlying heart disease, sex, age, access site, body mass index, and RV vs LV approach. RESULTS: The analysis revealed an overall complication rate of 4.1%. Serious life-threatening cardiac complications occurred in <1% of EMBs, with tamponade necessitating pericardiocentesis in 0.2% and urgent cardiac surgery in 0.1% of the procedures. Minor complications occurred in 3.3% of the overall population and were more often encountered during LV EMBs (3.9%) and when the native heart was sampled (5.3%). CONCLUSIONS: In experienced hands, LV and RV EMB for heart transplantation rejection surveillance and cardiomyopathy diagnosis is a safe procedure with low risk of complications. Older, female patients and those undergoing native heart EMB were more prone to complications following EMB.

Deferral of Coronary Revascularization in Patients With Reduced Ejection Fraction Based on Physiological Assessment: Impact on Long-Term Survival.

Background Deferring revascularization in patients with nonsignificant stenoses based on fractional flow reserve (FFR) is associated with favorable clinical outcomes up to 15 years. Whether this holds true in patients with reduced left ventricular ejection fraction is unclear. We aimed to investigate whether FFR provides adjunctive clinical benefit compared with coronary angiography in deferring revascularization of patients with intermediate coronary stenoses and reduced left ventricular ejection fraction. Methods and Results Consecutive patients with reduced left ventricular ejection fraction (≤50%) undergoing coronary angiography between 2002 and 2010 were screened. We included patients with at least 1 intermediate coronary stenosis (diameter stenosis ≥40%) in whom revascularization was deferred based either on angiography plus FFR (FFR guided) or angiography alone (angiography guided). The primary end point was the cumulative incidence of all-cause death at 10 years. The secondary end point (incidence of major adverse cardiovascular and cerebrovascular events) was a composite of all-cause death, myocardial infarction, any revascularization, and stroke. A total of 840 patients were included (206 in the FFR-guided group and 634 in the angiography-guided group). Median follow-up was 7 years (interquartile range, 3.22-11.08 years). After 1:1 propensity-score matching, baseline characteristics between the 2 groups were similar. All-cause death was significantly lower in the FFR-guided group compared with the angiography-guided group (94 [45.6%] versus 119 [57.8%]; hazard ratio [HR], 0.65 [95% CI, 0.49-0.85]; P<0.01). The rate of major adverse cardiovascular and cerebrovascular events was lower in the FFR-guided group (123 [59.7%] versus 139 [67.5%]; HR, 0.75 [95% CI, 0.59-0.95]; P=0.02). Conclusions In patients with reduced left ventricular ejection fraction, deferring revascularization of intermediate coronary stenoses based on FFR is associated with a lower incidence of death and major adverse cardiovascular and cerebrovascular events at 10 years.

Absolute coronary flow and microvascular resistance reserve in patients with severe aortic stenosis.

BACKGROUND: Development of left ventricle (LV) hypertrophy in aortic stenosis (AS) is accompanied by adaptive coronary flow regulation. We aimed to assess absolute coronary flow, microvascular resistance, coronary flow reverse (CFR) and microvascular resistance reserve (MRR) in patients with and without AS. METHODS: Absolute coronary flow and microvascular resistance were measured by continuous thermodilution in 29 patients with AS and 29 controls, without AS, matched for age, gender, diabetes and functional severity of epicardial coronary lesions. Myocardial work, total myocardial mass and left anterior descending artery (LAD)-specific mass were quantified by echocardiography and cardiac-CT. RESULTS: Patients with AS presented a significantly positive LV remodelling with lower global longitudinal strain and global work efficacy compared with controls. Total LV myocardial mass and LAD-specific myocardial mass were significantly higher in patients with AS (p=0.001). Compared with matched controls, absolute resting flow in the LAD was significantly higher in the AS cohort (p=0.009), resulting into lower CFR and MRR in the AS cohort compared with controls (p<0.005 for both). No differences were found in hyperaemic flow and resting and hyperaemic resistances. Hyperaemic myocardial perfusion (calculated as the ratio between the absolute coronary flow subtended to the LAD, expressed in mL/min/g), but not resting, was significantly lower in the AS group (p=0.035). CONCLUSIONS: In patients with severe AS and non-obstructive coronary artery disease, with the progression of LV hypertrophy, the compensatory mechanism of increased resting flow maintains adequate perfusion at rest, but not during hyperaemia. As a consequence, both CFR and MRR are significantly impaired.

Arrhythmic Storm Due to ICD Atrial Lead Malfunction.

We describe the case of a young woman with a dual-chamber implantable cardioverter-defibrillator for long-QT syndrome who was referred to our emergency department (Cardiovascular Research Centre of Aalst, Belgium) because of an "arrhythmic storm" caused by atrial lead fracture. This case highlights the importance of the correct choice of both the device type and the pacing modality. (Level of Difficulty: Intermediate.).

Pre-cath Laboratory Planning for Left Atrial Appendage Occlusion - Optional or Essential?

In the wake of rapid advancement in cardiovascular procedural technologies, physician-led preprocedural planning utilizing multi-modality imaging training is increasingly recognized as invaluable for procedural accuracy. Left atrial appendage occlusion (LAAO) is one such procedure in which complications such as device leak, cardiac injury, and device embolization can be decreased substantially with incorporation of physician driven imaging and digital tools. We discuss the benefits of cardiac CT and 3D printing in preprocedural planning for the Heart Team, as well as novel applications by physicians of intraprocedural 3D angiography and dynamic fusion imaging. Furthermore, incorporation of computational modeling and artificial intelligence (AI) may yield promise. For optimal patient-centric procedural success, we advocate for standardized preprocedural imaging planning by physicians within the Heart Team as an essential part of LAAO.

Prospective evaluation of the learning curve and diagnostic accuracy for Pre-TAVI cardiac computed tomography analysis by cardiologists in training: The LEARN-CT study.

BACKGROUND: To investigate the learning curve and the minimum number of cases required for a cardiologist in training to acquire the skills to an accurate pre-TAVI cardiac CT (CCT) analysis using a semi-automatic software. METHODS: In this prospective, observational study, 40 CCTs of patients scheduled for TAVI were independently evaluated twice by 5 readers (80 readings each, 400 in total): a certified TAVI-CT specialist served as the reference reader (RR) and 4 cardiology fellows (2 interventional and 2 non-invasive cardiac imaging) as readers. The primary outcome was the minimum number of cases required to achieve an accuracy in imaging interpretation ≥80%, defined as the agreement between each reader and the RR in both balloon and self-expandable valve size choice. The secondary outcomes were the intra- and inter-observer variability. RESULTS: After 50 readings (25 cases repeated twice) cardiology fellows were able to select the appropriate valve size with ≥ 80% of accuracy compared to the RR, independently of valve calcification, image quality and slice thickness. Learning curves of both interventional and non-invasive cardiac imaging fellows showed a similar trend. Cardiology fellows achieved a very high intra- and inter-observer reliability for both perimeter and area assessment, with an intraclass correlation coefficient (ICC) ranging from 0.96 to 0.99. CONCLUSIONS: Despite the individual differences, cardiology fellows required 50 readings (25 cases repeated twice) to get adequately skilled in the pre-TAVI CCT interpretation. These results provide valuable information for developing adequate training sessions and education protocols for both companies and cardiologists involved.

Contemporary Management of Stable Coronary Artery Disease.

Coronary artery disease (CAD) continues to be the leading cause of mortality and morbidity in developed countries. Assessment of pre-test probability (PTP) based on patient's characteristics, gender and symptoms, help to identify more accurate patient's clinical likelihood of coronary artery disease. Consequently, non-invasive imaging tests are performed more appropriately to rule in or rule out CAD rather than invasive coronary angiography (ICA). Coronary computed tomography angiography (CCTA) is the first-line non-invasive imaging technique in patients with suspected CAD and could be used to plan and guide coronary intervention. Invasive coronary angiography remains the gold-standard method for the identification and characterization of coronary artery stenosis. However, it is recommended in patients where the imaging tests are non-conclusive, and the clinical likelihood is very high, remembering that in clinical practice, approximately 30 to 70% of patients with symptoms and/or signs of ischemia, referred to coronary angiography, have non obstructive coronary artery disease (INOCA). In this contest, physiology and imaging-guided revascularization represent the cornerstone of contemporary management of chronic coronary syndromes (CCS) patients allowing us to focus specifically on ischemia-inducing stenoses. Finally, we also discuss contemporary medical therapeutic approach for secondary prevention. The aim of this review is to provide an updated diagnostic and therapeutic approach for the management of patients with stable coronary artery disease.

Performance of non-invasive myocardial work to predict the first hospitalization for de novo heart failure with preserved ejection fraction.

AIMS: Non-invasive myocardial work (MW) is a validated index of left ventricular (LV) systolic performance, incorporating afterload and myocardial metabolism. The role of MW in predicting the first hospitalization for de novo heart failure with preserved ejection fraction (HFpEF) is still unknown. We aim to investigate the diagnostic performance of MW to predict the first de novo HFpEF hospitalization in ambulatory individuals with preserved LV ejection fraction. METHODS AND RESULTS: Twenty-nine patients with transthoracic echocardiography performed at least 6 months before the first HFpEF hospitalization were compared with 29 matched controls. MW was derived as the area of pressure-strain loop using speckle-tracking and brachial artery blood pressure. Global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE) were collected. First HFpEF hospitalization and its combination with cardiovascular death [major adverse cardiovascular events (MACE)] and all-cause of death [major adverse events (MAE)] were assessed. At baseline, future HFpEF patients showed lower global work index, global constructive work, GWE, and higher GWW than controls (all P < 0.05). At admission vs. baseline, GWE significantly decreased, and GWW increased in the HFpEF group (P < 0.05), whereas no significant difference was observed in the controls over time. GWW, with a cut-off of 170 mmHg%, showed the largest area under the curve (AUC) to predict first HFpEF hospitalization [AUC = 0.80, 95% confidence interval (CI) 0.69-0.91, P < 0.001], MACE (AUC = 0.80, 95% CI 0.66-0.90, P < 0.001), and MAE (AUC = 0.79, 95% CI 0.62-0.88, P = 0.001). GWW > 170 mmHg% was associated with a 4-fold increase of MACE (HR = 4.5, 95% CI 1.59-13.12, P = 0.005) and a 3-fold higher risk of MAE (HR = 2.9, 95% CI 1.24-6.6, P = 0.014). CONCLUSIONS: In ambulatory patients with preserved LV ejection fraction and risk factors, GWW showed high accuracy to predict the first HFpEF hospitalization and its combination with mortality. The GWW routine assessment may be clinically helpful in patients with dyspnoea.

Microvascular Dysfunction in Patients With Type II Diabetes Mellitus: Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance Reserve.

Background: Coronary microvascular dysfunction (CMD) is an early feature of diabetic cardiomyopathy, which usually precedes the onset of diastolic and systolic dysfunction. Continuous intracoronary thermodilution allows an accurate and reproducible assessment of absolute coronary blood flow and microvascular resistance thus allowing the evaluation of coronary flow reserve (CFR) and Microvascular Resistance Reserve (MRR), a novel index specific for microvascular function, which is independent from the myocardial mass. In the present study we compared absolute coronary flow and resistance, CFR and MRR assessed by continuous intracoronary thermodilution in diabetic vs. non-diabetic patients. Left atrial reservoir strain (LASr), an early marker of diastolic dysfunction was compared between the two groups. Methods: In this observational retrospective study, 108 patients with suspected angina and non-obstructive coronary artery disease (NOCAD) consecutively undergoing elective coronary angiography (CAG) from September 2018 to June 2021 were enrolled. The invasive functional assessment of microvascular function was performed in the left anterior descending artery (LAD) with intracoronary continuous thermodilution. Patients were classified according to the presence of DM. Absolute resting and hyperemic coronary blood flow (in mL/min) and resistance (in WU) were compared between the two cohorts. FFR was measured to assess coronary epicardial lesions, while CFR and MRR were calculated to assess microvascular function. LAS, assessed by speckle tracking echocardiography, was used to detect early myocardial structural changes potentially associated with microvascular dysfunction. Results: The median FFR value was 0.83 [0.79-0.87] without any significant difference between the two groups. Absolute resting and hyperemic flow in the left anterior descending coronary were similar between diabetic and non-diabetic patients. Similarly, resting and hyperemic resistances did not change significantly between the two groups. In the DM cohort the CFR and MRR were significantly lower compared to the control group (CFR = 2.38 ± 0.61 and 2.88 ± 0.82; MRR = 2.79 ± 0.87 and 3.48 ± 1.02 for diabetic and non-diabetic patients respectively, [p < 0.05 for both]). Likewise, diabetic patients had a significantly lower reservoir, contractile and conductive LAS (all p < 0.05). Conclusions: Compared with non-diabetic patients, CFR and MRR were lower in patients with DM and non-obstructive epicardial coronary arteries, while both resting and hyperemic coronary flow and resistance were similar. LASr was lower in diabetic patients, confirming the presence of a subclinical diastolic dysfunction associated to the microcirculatory impairment. Continuous intracoronary thermodilution-derived indexes provide a reliable and operator-independent assessment of coronary macro- and microvasculature and might potentially facilitate widespread clinical adoption of invasive physiologic assessment of suspected microvascular disease.

Ultralow temperature cryoablation using near-critical nitrogen for cavotricuspid isthmus-ablation, first-in-human results.

INTRODUCTION: Cryoablation has evolved as a safe alternative to radiofrequency ablation in the treatment of several supraventricular arrhythmias and has potential advantages, yet is limited by the properties of the cryogen used. We investigated a novel ultralow temperature cryoablation (ULTC) system using nitrogen near its liquid-vapor critical point as a freezing source, achieving temperatures as low as -196 degrees Celsius in a long linear catheter with a continuous energy release. Initial safety, procedural and efficacy outcomes of ULTC are described in patients undergoing cavotricuspid isthmus (CTI) ablation. METHODS AND RESULTS: The Cryocure studies (NCT02355106, NCT02839304) are prospective, single-arm, multi-center, first-in-human clinical studies in 17 patients with atrial flutter (AFL) and 13 patients with atrial fibrillation (AF). A total of 30 patients, mean age 65 ± 8 years old and 67% male, were enrolled and underwent ablation of the CTI. Acute success, defined as the confirmation of stable bidirectional conduction block across the CTI, was achieved in all 30 patients. After 12 months of follow-up, 14 out of 17 AFL patients remained free from any AFL. One (3.3%) procedure-related but not device-related serious adverse event was reported, involving transient inferolateral ST-elevation associated with temporary AV conduction block. CONCLUSION: In this first-in-human clinical study the safety and performance results demonstrate the capabilities of ultralow temperature near-critical nitrogen as an effective energy source for CTI ablation. Ongoing, larger, studies should confirm our findings and evaluate the capabilities to create linear and focal transmural lesions in other arrhythmias.