Running on empty: Factors underpinning impaired cardiac output reserve in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is frequently attributed etiologically to an underlying left ventricular (LV) diastolic dysfunction, although its pathophysiology is far more complex and can exhibit significant variations among patients. This review endeavours to systematically unravel the pathophysiological heterogeneity by illustrating diverse mechanisms leading to an impaired cardiac output reserve, a central and prevalent haemodynamic abnormality in HFpEF patients. Drawing on previously published findings from our research group, we propose a pathophysiology-guided phenotyping based on the presence of: (1) LV diastolic dysfunction, (2) LV systolic pathologies, (3) arterial stiffness, (4) atrial impairment, (5) right ventricular dysfunction, (6) tricuspid valve regurgitation, and (7) chronotopic incompetence. Tailored to each specific phenotype, we explore various potential treatment options such as antifibrotic medication, diuretics, renal denervation and more. Our conclusion underscores the pivotal role of cardiac output reserve as a key haemodynamic abnormality in HFpEF, emphasizing that by phenotyping patients according to its individual pathomechanisms, insights into personalized therapeutic approaches can be gleaned.

Photon-Counting Detector CT Virtual Monoenergetic Images for Coronary Artery Stenosis Quantification: Phantom and In Vivo Evaluation.

BACKGROUND. Calcium blooming causes stenosis overestimation on coronary CTA. OBJECTIVE. The purpose of this article was to evaluate the impact of virtual monoenergetic imaging (VMI) reconstruction level on coronary artery stenosis quantification using photon-counting detector (PCD) CT. METHODS. A phantom containing two custom-made vessels (representing 25% and 50% stenosis) underwent PCD CT acquisitions without and with simulated cardiac motion. A retrospective analysis was performed of 33 patients (seven women, 26 men; mean age, 71.3 ± 9.0 [SD] years; 64 coronary artery stenoses) who underwent coronary CTA by PCD CT followed by invasive coronary angiography (ICA). Scans were reconstructed at nine VMI energy levels (40-140 keV). Percentage diameter stenosis (PDS) was measured, and bias was determined from the ground-truth stenosis percentage in the phantom and ICA-derived quantitative coronary angiography measurements in patients. Extent of blooming artifact was measured in the phantom and in calcified and mixed plaques in patients. RESULTS. In the phantom, PDS decreased for 25% stenosis from 59.9% (40 keV) to 13.4% (140 keV) and for 50% stenosis from 81.6% (40 keV) to 42.3% (140 keV). PDS showed lowest bias for 25% stenosis at 90 keV (bias, 1.4%) and for 50% stenosis at 100 keV (bias, -0.4%). Blooming artifacts decreased for 25% stenosis from 61.5% (40 keV) to 35.4% (140 keV) and for 50% stenosis from 82.7% (40 keV) to 52.1% (140 keV). In patients, PDS for calcified plaque decreased from 70.8% (40 keV) to 57.3% (140 keV), for mixed plaque decreased from 69.8% (40 keV) to 56.3% (140 keV), and for noncalcified plaque was 46.6% at 40 keV and 54.6% at 140 keV. PDS showed lowest bias for calcified plaque at 100 keV (bias, 17.2%), for mixed plaque at 140 keV (bias, 5.0%), and for noncalcified plaque at 40 keV (bias, -0.5%). Blooming artifacts decreased for calcified plaque from 78.4% (40 keV) to 48.6% (140 keV) and for mixed plaque from 73.1% (40 keV) to 44.7% (140 keV). CONCLUSION. For calcified and mixed plaque, stenosis severity measurements and blooming artifacts decreased at increasing VMI reconstruction levels. CLINICAL IMPACT. PCD CT with VMI reconstruction helps overcome current limitations in stenosis quantification on coronary CTA.

A nationwide trend analysis on the usage of endomyocardial biopsy.

BACKGROUND: Endomyocardial biopsy (EMB) is a safe procedure performed in diagnostic work-up of cardiac disease. HYPOTHESIS: Data regarding temporal trends of total numbers, characteristics, in-hospital outcomes, and complications of patients undergoing EMB are sparse. METHODS: The nationwide German inpatient sample (2005-2019) was used for this analysis. Patient cases of EBM during the 5-year cycles from 2005 to 2009, 2010 to 2014, and 2015 to 2019 were compared, and temporal trends regarding total numbers and presumable major and minor EMB-associated complications were investigated. RESULTS: Overall, 67 745 EMB were performed in Germany 2005-2019. Total number of EMB increased from 3083 in 2005 to 5646 in 2019 (ß 0.40 [95% confidence interval [CI] 0.37-0.43], p < .001). Among these EMB, 19 083 (28.2%) were performed during the period 2005-2009, 22 867 (33.7%) 2010-2014, and 25 795 (38.1%) between 2015 and 2019. The proportion of patients aged ≥70 years was highest 2015-2019 (2005-2009: 9.3%; 2010-2014: 13.8%; 2015-2019: 16.1%, p < .001) and the most aggravated comorbidity profile (Charlson Comorbidity Index 2.25 ± 1.93; 2.67 ± 2.14; 3.01 ± 2.29, p < .001) was also detected 2015-2019. Major complications occurred less often in the period 2015-2019 compared to 2005-2009 (odds ratio [OR] 0.921 [95% CI 0.893-0.950], p < .001), whereas minor complications were more frequently observed between 2015 and 2019 (OR 1.067 [95% CI 1.042-1.093], p < .001). While a decrease in major complications was detected irrespective of age, an increase in minor complications was identified only in patients between 30-59 years. CONCLUSIONS: Annual numbers of EMB increased significantly in Germany 2005-2019. Patients who underwent EMB in recent years were older and showed an aggravated comorbidity profile accompanied by fewer major complications, underscoring safety of the procedure.

A multidisciplinary pulmonary embolism response team (PERT): first experience from a single center in Germany.

BACKGROUND: Over the last few years, the concept of multidisciplinary pulmonary embolism response teams (PERTs) has emerged to encounter the increasing variety and complexity in managing acute pulmonary embolism (PE). PURPOSE: To investigate PERT's composition and added clinical value in a university center in Germany. METHODS: Over 4 years (01/2019-11/2022), patients with confirmed PE were enrolled in a prospective single-center cohort study (PERT Mainz). We investigated the composition of PERT and compared, after propensity score matching, patients with acute PE before and after the initiation of PERT at our Medical University Centre. The primary outcome was in-hospital PE-related mortality. RESULTS: From 2019 to 2022, 88 patients with acute PE with a PERT decision were registered. Of those, 13 (14.8%) patients died during the in-hospital stay. Patients evaluated by a PERT had a median age of 68; 48.9% were females, and 21.7% suffered from malignancy. Right ventricular dysfunction was present in 76.1% of all patients. In total, 42.0% were classified as intermediate-high-risk PE and 11.4% as high-risk PE. First PERT contact mainly originated from emergency departments (33.3%) and intensive care units (30.0%), followed by chest pain units (21.3%) and regular wards (12.0%). The participation rate of medical specialties demonstrated that cardiologists (100%) or cardiac/vascular surgeons (98.6%) were included in almost all PERT consultations, followed by radiologists (95.9%) and anesthesiologists (87.8%). Compared to the PERT era, more patients in the pre-PERT era were classified as simplified pulmonary embolism severity index (sPESI) ≥ 1 (78.4% vs 71.6%) and as high-risk PE according to ESC 2019 guidelines (18.2% vs. 11.4%). In the pre-PERT era, low- and intermediate-low patients with PE received more frequently advanced reperfusion therapies such as systemic thrombolysis or surgical embolectomy compared to the PERT era (10.7% vs. 2.5%). Patients in the pre-PERT were found to have a considerably higher all-cause mortality and PE-related mortality rate (31.8% vs. 14.8%) compared to patients in the PERT era (22.7% vs. 13.6%). After propensity matching (1:1) by including parameters as age, sex, sPESI, and ESC risk classes, univariate regression analyses demonstrated that the PE management based on a PERT decision was associated with lower risk of all-cause mortality (OR, 0.37 [95%CI 0.18-0.77]; p = 0.009). For PE-related mortality, a tendency for reduction was observed (OR, 0.54 [95%CI 0.24-1.18]; p = 0.121). CONCLUSION: PERT implementation was associated with a lower risk of all-cause mortality rate in patients with acute PE. Large prospective studies are needed further to explore the impact of PERTs on clinical outcomes.

In-hospital Outcomes of Rotational Atherectomy in ST-Elevation Myocardial Infarction: Results From the Multicentre ROTA-STEMI Network.

BACKGROUND: Although the use of rotational atherectomy (RA) is off-label in the setting of ST-elevation myocardial infarction (STEMI), it can be the only option in severely calcified culprit lesions to achieve procedural success. We sought to investigate the safety and feasibility of RA during primary percutaneous coronary intervention (PPCI). METHODS: This was a retrospective observational study of patients who underwent RA during PPCI from 12 European centres. The main outcomes were procedural success (defined as successful stent implantation with final thrombolysis in myocardial infarction [TIMI] flow 3 and residual stenosis < 30%) and in-hospital mortality. A comparison of patients presenting with and without shock was performed. RESULTS: In 104 patients with RA during STEMI, the mean age was 72.8 ± 9.1 years, and 35% presented with cardiogenic shock. Bailout RA was performed in 76.9% of cases. Mean burr size was 1.42 ± 0.21 mm. Procedural success was achieved in 86.5% of cases, with no difference between shocked and nonshocked patients (94.4% vs 82.4%; P = 0.13). In-hospital stent thrombosis occurred in 0.96%, perforation in 1.9% and burr entrapment in 2.9% of cases. In spite of equally high procedural success, in-hospital mortality was higher in shocked (50%) compared with nonshocked patients (1.5%; P < 0.0001). CONCLUSIONS: Patients presenting with STEMI requiring RA, represent a high-risk population, frequently presenting with cardiogenic shock. In this analysis of selected patients, RA was performed as a bailout strategy in the majority, and, as such, RA seems to be feasible with a high procedural success rate. In the absence of cardiogenic shock, RA-facilitated PCI seems to be associated with low in-hospital mortality.

Comprehensive vasodilatation in women with acute heart failure: Novel insights from the GALACTIC randomized controlled trial.

AIMS: Sex-specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF therapies in women and men separately. METHODS AND RESULTS: We performed a pre-defined sex-specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilatation versus usual care in an international, multicentre, open-label, blinded endpoint trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 vs. 76 years), had a lower body weight (median 64.5 vs. 77.6 kg) and lower estimated glomerular filtration rate (median 48 vs. 54 ml/min/1.73 m2 ). The primary endpoint, a composite of all-cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62, 95% confidence interval 1.05-2.50; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up-titration of renin-angiotensin-aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men). CONCLUSION: Rapid up-titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all-cause mortality and rehospitalization for AHF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, unique identifier NCT00512759.

Diseases of the Coronary Microcirculation: Diagnosis and Treatment.

BACKGROUND: Coronary microvascular dysfunction (CMD) comprises a variety of pathogenic mechanisms that impair the microcirculation of the heart. Clinical studies have shown that 30-50% of patients suffering from myocardial ischemia without significant coronary artery stenosis have CMD. The disease is associated with ele - vated mortality and poor quality of life. Whenever a patient presents with symptoms of angina pectoris and no underlying disease is detected by the usual methods, CMD should be considered a possible cause. METHODS: This review is based on publications retrieved by a selective search in PubMed and on current international guidelines and recommendations of specialty societies. RESULTS: The diagnosis of CMD is based on objective evidence of a microvascular origin of symptoms. The guidelines contain a class IIa recommendation for invasive coronary flow reserve and microvascular resistance measurements. Noninvasive tests such as positron emission tomography and cardiac magnetic resonance imaging are less accurate and are given a class IIb recommendation. No highquality therapeutic trials are available to date, and the treatment of CMD is thus based on that of chronic coronary syndrome. Lifestyle modification is performed to reduce risk factors. Patients with an abnormal coronary flow reserve or elevated microvascular resistance can be treated with an ACE inhibitor or angiotensin receptor blocker. Beta-blockers and calcium channel antagonists can relieve angina pectoris. Statins lower the LDL level and have positive pleiotropic effects. First-line treatment can be supplemented with further medications. CONCLUSION: Approximately 25% of patients with CMD have symptoms that do not respond to intensive treatment with the currently available modalities. New treatments, including interventional therapies, are being studied. Their long-term benefit remains to be assessed and compared to that of the existing methods.

Temporal trends of case-fatality in patients undergoing dual-injection coronary chronic total occlusion recanalization.

AIMS: Recently, interventional techniques and material to treat chronic total occlusion (CTO) with percutaneous coronary intervention (PCI) have evolved significantly. Nevertheless, it is still unknown whether this progress improved treatment success and patients' outcome. In a nationwide sample, we sought to analyze trends of patients' characteristics, complications and in-hospital case-fatality of patients undergoing CTO revascularization in Germany. METHODS AND RESULTS: We analyzed data on characteristics, treatments, and in-hospital outcomes for all coronary artery disease (CAD) patients (ICD-code I25) undergoing dual-injection CTO recanalization (OPS procedural code: 8-839.9) in Germany from 2009 to 2020. Overall, 4,998,457 inpatients aged ≥ 18 years with diagnosis of CAD were treated in German hospitals in this period. Among these, 52,879 patients (1.1%) underwent CTO recanalization. Annual number of CTO PCIs increased from 1263 in 2009 to 6435 in 2020 (ß 3.48 [95% CI 3.44-3.52]; p < 0.001) in parallel with a significant decrease of case-fatality (2.2% in 2009 to 1.4% in 2020; ß - 0.60 [95% CI - 0.82 to - 0.39]; p < 0.001). Overall, 754 (1.4%) patients with CTO recanalization died during the in-hospital stay and in-hospital case-fatality grew exponentially with age (ß 0.82 [95% CI 0.73-0.90]; p < 0.001). Significant predictors of in-hospital case fatality with an OR > 3 were cancer, stroke, hemopericardium, acute renal failure, pulmonary embolism and shock. CONCLUSION: Annual number of CTO procedures performed in Germany increased from 2009 to 2020 with a concomitant anti-proportional decrease in the case-fatality. Our findings may help to draw more attention to predictors of in-hospital case fatality in patients hospitalized for CTO recanalization.

Coronary Venous Pressure and Microvascular Hemodynamics in Patients With Microvascular Angina: A Randomized Clinical Trial.

Importance: The role of the coronary venous circulation in regulating myocardial perfusion and its potential in treating microvascular angina is unexplored. Objective: To evaluate whether an increase in coronary venous pressure modifies microvascular resistance in patients with microvascular angina. Design, Setting, and Participants: This was a blinded, sham-controlled, crossover, randomized clinical trial that enrolled participants between November 2021 and January 2023. Participants for this physiology end point study were recruited from the Cardiology Center of the University of Medicine in Mainz, Germany. Patients with moderate/severe angina pectoris (Canadian Cardiovascular Society class 2-4) due to microvascular dysfunction (as defined by the thermodilution-based index of microvascular resistance >25 mm Hg × s). Exclusion criteria were epicardial coronary disease, second- and third-degree atrioventricular block, severe valvular heart disease, cardiomyopathy, and pulmonary or kidney disease. Intervention: Inflation of an undersized balloon placed in the cardiac coronary sinus (CS), hereafter referred to as balloon and the deflated balloon in the right atrium, referred to as sham. Measurements were performed at rest and during maximal coronary hyperemia. Both patients and final assessors were blinded to the randomization sequence. Main Outcomes and Measures: Hemodynamic parameters, including aortic (Pa) and distal (Pd) coronary pressure, coronary sinus pressure (Pcs), right atrial pressure (Pra), and the mean transit time (inverse of blood flow [Tmn]), were measured. Results: A total of 20 patients (median [IQR] age, 69 [64-75] years; 11 female [55.0%]) were included in the study. Two patients (10%) had diabetes, 6 (30%) had hypercholesterolemia, 15 (75%) had hypertension, and 3 (15%) were active smokers. The inflation of the CS balloon caused a significant increase in CS pressure at rest and during hyperemia (300% and 317% increase, respectively, compared with sham, both P < .001), a decrease in hyperemic distal coronary pressure (median [IQR], sham: 92 [80-100] mm Hg; balloon: 79 [75-93] mm Hg; P = .01) and mean transit time (sham: 0.39 [0.23-0.62] s; balloon: 0.26 [0.17-0.46] s; P = .008). As a result, CS occlusion led to a decrease in both resting coronary resistance (median [IQR], sham: 59 [37-87] mm Hg × s; balloon: 42 [31-67] mm Hg × s; P = .005) and the primary end point hyperemic coronary resistance (mean [IQR], sham: 31 [23-53] mm Hg × s; balloon: 14 [8-26] mm Hg × s; P < .001). Conclusion and Relevance: Increased coronary venous pressure led to a reduction of microvascular resistances in patients with microvascular angina, a mechanism with potential implications for the therapy of this complex disease. Trial Registration: ClinicalTrials.gov Identifier: NCT05034224.

Evaluation of right-ventricular function by two-dimensional echocardiography and two-dimensional speckle-tracking echocardiography in patients with successful RCA CTO recanalization.

OBJECTIVES: Chronic total occlusion (CTO) of the right coronary artery (RCA) is common in patients with coronary artery disease. Although revascularization techniques and success rates have improved significantly in recent years, there are still no studies investigating possible effects of successful recanalization of RCA CTO on the right-ventricular (RV) function. With this study, we aimed to evaluate RV function after recanalization of the RCA by two-dimensional transthoracic echocardiography (2DE) and additional two-dimensional speckle-tracking echocardiography (2DSTE). METHODS AND RESULTS: Our analysis included 102 patients undergoing successful RCA CTO recanalization at the University Medical Center of Mainz. All patients underwent 2DE and 2DSTE to assess RV function before PCI procedure and 6 months after successful revascularization. We found an altered RV function in our collective at baseline assessed by 2DSTE with a significant improvement at 6 month follow-up (baseline RV free wall strain: - 20.7 [- 6.3 to - 32.0] % vs. - 23.4 [- 8.3 to - 39.3] % at follow-up, p < 0.001 and baseline RV global strain - 15.9 [- 6.0 to - 25.7] % vs. - 17.9 [- 7.0 to - 29.5] % at follow-up, p < 0.001). CONCLUSION: RV function was altered in patients with RCA CTO and showed significant improvement after successful recanalization. We also noticed an improvement in patient-reported clinical symptoms. Our study suggests that CTO procedure is a beneficial treatment option in symptomatic patients with RCA CTO.

Sex-related differences in outcome after left atrial appendage occlusion: Insights from Europe and the EWOLUTION registry.

BACKGROUND: Women with atrial fibrillation (AF) generally experience worse symptoms, poorer quality of life, and have a higher risk of stroke and death. There is limited availability of sex-related differences regarding left atrial appendage occlusion (LAAO). AIMS: The aim of this study was to evaluate the sex-related differences in patients undergoing LAAO in EWOLUTION. METHODS: A total of 1025 patients scheduled for elective LAAO therapy employing the WATCHMAN Gen 2.5 prospectively consented for participation; 1005 patients received a successful implant and were followed for 2 years. As we detected sex-related differences in baseline data we performed a propensity score matching. The primary endpoint is a combined endpoint of survival free from mortality, major bleeding, ischemic stroke, transitory ischemic attack (TIA) and systemic embolization (SE) up to 2-year clinical follow-up. Secondary Endpoints were periprocedural data and overall 2-year survival. RESULTS: Women were older but had less often vascular disease and hemorrhagic stroke. There was no sex-related significant difference after LAAO at 2 years in the combined endpoint of survival free from mortality, major bleeding, ischemic stroke, TIA, and SE (female vs. male: 79% vs.76%, p = 0.24) or in overall survival (female vs. male: 85% vs. 82%, p = 0.16). Procedural data showed a higher sealing rate after the implantation in women (complete sealing female 94% vs. male 90%, p = 0.033), significantly more pericardial effusions (female 1.2% vs. male 0.2%, p = 0.031) and a similar periprocedural risk profile. CONCLUSIONS: Females undergoing LAAO differ in various baseline variables, but after adjustment, we observed similar safety and efficacy of LAAO with no significant difference in long-term outcomes between women and men.

Heart rate variability: reference values and role for clinical profile and mortality in individuals with heart failure.

AIMS: To establish reference values and clinically relevant determinants for measures of heart rate variability (HRV) and to assess their relevance for clinical outcome prediction in individuals with heart failure. METHODS: Data from the MyoVasc study (NCT04064450; N = 3289), a prospective cohort on chronic heart failure with a highly standardized, 5 h examination, and Holter ECG recording were investigated. HRV markers were selected using a systematic literature screen and a data-driven approach. Reference values were determined from a healthy subsample. Clinical determinants of HRV were investigated via multivariable linear regression analyses, while their relationship with mortality was investigated by multivariable Cox regression analyses. RESULTS: Holter ECG recordings were available for analysis in 1001 study participants (mean age 64.5 ± 10.5 years; female sex 35.4%). While the most frequently reported HRV markers in literature were from time and frequency domains, the data-driven approach revealed predominantly non-linear HRV measures. Age, sex, dyslipidemia, family history of myocardial infarction or stroke, peripheral artery disease, and heart failure were strongly related to HRV in multivariable models. In a follow-up period of 6.5 years, acceleration capacity [HRperSD 1.53 (95% CI 1.21/1.93), p = 0.0004], deceleration capacity [HRperSD: 0.70 (95% CI 0.55/0.88), p = 0.002], and time lag [HRperSD 1.22 (95% CI 1.03/1.44), p = 0.018] were the strongest predictors of all-cause mortality in individuals with heart failure independently of cardiovascular risk factors, comorbidities, and medication. CONCLUSION: HRV markers are associated with the cardiovascular clinical profile and are strong and independent predictors of survival in heart failure. This underscores clinical relevance and interventional potential for individuals with heart failure. GOV IDENTIFIER: NCT04064450.

5-Year Outcomes After Bioresorbable Coronary Scaffolds Implanted With Improved Technique.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) were designed to improve late event-free survival compared with metallic drug-eluting stents. However, initial trials demonstrated worse early outcomes with BVS, in part due to suboptimal technique. In the large-scale, blinded ABSORB IV trial, polymeric everolimus-eluting BVS implanted with improved technique demonstrated noninferior 1-year outcomes compared with cobalt chromium everolimus-eluting stents (CoCr-EES). OBJECTIVES: This study sought to evaluate the long-term outcomes from the ABSORB IV trial. METHODS: We randomized 2,604 patients at 147 sites with stable or acute coronary syndromes to BVS with improved technique vs CoCr-EES. Patients, clinical assessors, and event adjudicators were blinded to randomization. Five-year follow-up was completed. RESULTS: Target lesion failure at 5 years occurred in 216 (17.5%) patients assigned to BVS and 180 (14.5%) patients assigned to CoCr-EES (P = 0.03). Device thrombosis within 5 years occurred in 21 (1.7%) BVS and 13 (1.1%) CoCr-EES patients (P = 0.15). Event rates were slightly greater with BVS than CoCr-EES through 3-year follow-up and were similar between 3 and 5 years. Angina, also centrally adjudicated, recurred within 5 years in 659 patients (cumulative rate 53.0%) assigned to BVS and 674 (53.3%) patients assigned to CoCr-EES (P = 0.63). CONCLUSIONS: In this large-scale, blinded randomized trial, despite the improved implantation technique, the absolute 5-year rate of target lesion failure was 3% greater after BVS compared with CoCr-EES. The risk period for increased events was limited to 3 years, the time point of complete scaffold bioresorption; event rates were similar thereafter. Angina recurrence after intervention was frequent during 5-year follow-up but was comparable with both devices.(Absorb IV Randomized Controlled Trial; NCT02173379).

Six-months clinical and intracoronary imaging follow-up after reverse T and protrusion or double-kissing and crush stenting for the treatment of complex left main bifurcation lesions.

Background: There is a debate regarding the best stent strategy for unprotected distal left main (LM) bifurcation disease. Among two-stent techniques, double-kissing and crush (DKC) is favored in current guidelines but is complex and requires expertise. Reverse T and Protrusion (rTAP) was shown to be a comparable strategy regarding short-term efficacy and safety, but with reduced procedural complexity. Aim: To compare rTAP vs. DKC by optical coherence tomography (OCT) on the intermediate term. Methods: 52 consecutive patients with complex unprotected LM stenoses (Medina 0,1,1 or 1,1,1) were randomized to either DKC or rTAP and followed-up for a median of 189[180-263] days for clinical and OCT outcomes. Results: At follow-up OCT showed similar change in the side branch (SB) ostial area (primary endpoint). The confluence polygon showed a higher percentage of malapposed stent struts in the rTAP group that did not reach statistical significance (rTAP: 9.7[4.4-18.3] % vs. DKC: 3[0.07-10.9] %; p = 0.064). It also showed a trend towards larger neointimal area relative to the stent area (DKC: 8.8 [6.9 to 13.4] % vs. rTAP: 6.5 [3.9 to 8.9] %; p = 0.07), and smaller luminal area (DKC: 9.54[8.09-11.07] mm2 vs. rTAP: 11.21[9.53-12.42] mm²; p = 0.09) in the DKC group. The minimum luminal area in the parent vessel distal to the bifurcation was significantly smaller in the DKC group (DKC: 4.64 [3.64 to 5.34] mm² vs. rTAP: 6.76 [5.20 to 7.29] mm²; p = 0.03). This segment also showed a trend for smaller stent areas (p = 0.05 to 0.09), and a bigger neointimal area relative to the stent area (DKC: 8.94 [5.43 to 10.5]% vs. rTAP: 4.75 [0.08 to 8.5]%; p = 0.06) in the DKC patients. The incidence of clinical events was comparably low in both groups. Conclusion: At 6-months, OCT showed a similar change in the SB ostial area (primary endpoint) in rTAP compared to DKC. There was also a trend for smaller luminal areas in the confluence polygon and the distal parent vessel, and a larger neointimal area relative to the stent area, in DKC, along with a tendency for more malapposed stent struts in rTAP. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03714750, identifier: NCT03714750.

Comparison of Coronary Intravascular Lithotripsy and Rotational Atherectomy in the Modification of Severely Calcified Stenoses.

Debulking techniques are often necessary for successful lesion preparation in percutaneous coronary intervention. The aim of this study was to compare plaque modification of severely calcified lesions by coronary intravascular lithotripsy (IVL) with that of rotational atherectomy (RA) using optical coherence tomography (OCT). ROTA.shock was a 1:1 randomized, prospective, double-arm, multicenter noninferiority trial designed to compare final minimal stent area after IVL with RA for lesion preparation in percutaneous coronary interventional treatment of severely calcified lesions. On the basis of OCT acquired before and immediately after IVL or RA in 21 of the 70 patients included, we performed a detailed analysis of the modification of the calcified plaque. After RA and IVL, calcified plaque fractures were present in 14 of the patients (67%), with a significantly greater number of fractures after IVL (3.23 ± 0.49) than after RA (1.67 ± 0.52; p < 0.001). Plaque fractures after IVL were longer than after RA (IVL: 1.67 ± 0.43 mm vs RA: 0.57 ± 0.55 mm; p = 0.01), resulting in a greater total volume of the fractures (IVL: 1.47 ± 0.40 mm3 vs RA: 0.48 ± 0.27 mm3; p = 0.003). Use of RA was associated with a greater acute lumen gain than was use of IVL (RA: 0.46 ± 0.16 mm2 vs IVL: 0.17 ± 0.14 mm2; p = 0.03). In conclusion, we were able to show differences in plaque modification of calcified coronary lesions by OCT: although RA leads to a greater acute lumen gain, IVL induces more and longer fractures of the calcified plaque.

Randomized, crossover, controlled trial on the modulation of cardiac coronary sinus hemodynamics to develop a new treatment for microvascular disease: Protocol of the MACCUS trial.

Background: Microvascular angina (MVA) is a frequent condition for which our understanding of the disease pathophysiology and therapeutic perspectives remain unsatisfactory. The current study is designed to test whether an improvement in microvascular resistances could be achieved by elevating backward pressure in the coronary venous system, based on the hypothesis that an increase in hydrostatic pressure could cause a dilatation of the myocardial arterioles, resulting in a reduction of vascular resistances. This approach might have potential clinical implications, as it might suggest that interventions aimed at increasing coronary sinus (CS) pressure might result in a decrease in angina in this subset of patients. The aim of our single-center, sham-controlled, crossover randomized trial is to investigate the effect of an acute increase in CS pressure on a number of parameters of coronary physiology, including parameters of coronary microvascular resistance and conductance. Methods and analysis: A total of 20 consecutive patients with angina pectoris and coronary microvascular dysfunction (CMD) will be enrolled in the study. Hemodynamic parameters including aortic and distal coronary pressure, CS and right atrial pressure, and the coronary microvascular resistance index will be measured at rest and during hyperemia in a randomized crossover design during incomplete balloon occlusion ("balloon") and with the deflated balloon in the right atrium ("sham"). The primary end point of the study is the change in index of microvascular resistances (IMR) after acute modulation of CS pressure, while key secondary end points include changes in the other parameters. Discussion: The aim of the study is to investigate whether occlusion of the CS is associated with a decrease in IMR. The results will provide mechanistic evidence for the development of a treatment for patients with MVA. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05034224.

Incidence and risk factors of myocarditis in hospitalized patients with COVID-19.

Myocarditis as cardiac involvement in coronavirus disease 2019 (COVID-19)-infection is well known. Real-world data about incidence in hospitalized COVID-19-patients and risk factors for myocarditis in COVID-19-patients are sparse. We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19-diagnosis in Germany in 2020 and stratified them for myocarditis. Overall, 176 137 hospitalizations (52.3% males, 53.6% aged ≥70 years) with confirmed COVID-19-infection were coded in Germany in 2020 and among them, 226 (0.01%) had myocarditis (incidence: 1.28 per 1000 hospitalization-cases). Absolute numbers of myocarditis increased, while relative numbers decreased with age. COVID-19-patients with myocarditis were younger (64.0 [IQR: 43.0/78.0] vs. 71.0 [56.0/82.0], p < 0.001). In-hospital case-fatality was 1.3-fold higher in COVID-19-patients with than without myocarditis (24.3% vs. 18.9%, p = 0.012). Myocarditis was independently associated with increased case-fatality (OR: 1.89 [95% CI: 1.33-2.67], p < 0.001). Independent risk factors for myocarditis were age <70 years (OR: 2.36 [95% CI: 1.72-3.24], p < 0.001), male sex (1.68 [95% CI: 1.28-2.23], p < 0.001), pneumonia (OR: 1.77 [95% CI: 1.30-2.42], p < 0.001), and multisystemic inflammatory COVID-19-infection (OR: 10.73 [95% CI: 5.39-21.39], p < 0.001). The incidence of myocarditis in hospitalized COVID-19-patients in Germany was 1.28 cases per 1000 hospitalizations in 2020. Risk factors for myocarditis in COVID-19 were young age, male sex, pneumonia, and multisystemic inflammatory COVID-19-infection. Myocarditis was independently associated with increased case-fatality.