Aortic valved homograft degeneration: surgical or transcatheter approach for repeat aortic valve replacement?

OBJECTIVES: Aortic valved allografts (homografts) have been used alternatively to mechanical or biological valve prostheses in expectation of better durability; however, homograft valves do degenerate, and redo procedures have proven challenging due to heavy wall calcification. The aim of the study was to compare the outcome of open surgical (SAVR) and transcatheter aortic valve replacement (TAVR) in degenerated homografts. METHODS: Between 1993 and 2022, 81 patients underwent repeat aortic valve procedures having previously received an aortic homograft. The redo had become necessary due to regurgitation in 85% and stenosis in 15%. Sixty-five percent underwent open surgery, 35% TAVR. RESULTS: Isolated SAVR was possible in 79%, and root procedures were necessary in 21%. TAVR was performed in 79% via transfemoral and 21% via transapical access. Median prosthetic valve size was 23 (22.3-23.2) mm in the SAVR and 26 (25.2-26.9) in the TAVR group. Thirty-day mortality was 0% in the TAVR and 7% in the SAVR group (P = n.s.). TAVR showed a significantly better outcome concerning prolonged ventilation (0 vs 21%, P = 0.013) as well as ICU (1 vs 2 days; P < 0.001) and in-hospital stay (10.5 vs 13 days; P = 0.028). Five-year survival was statistically comparable between groups, and no severe leakage was observed. CONCLUSIONS: SAVR following structural homograft degeneration shows acceptable results, but the perioperative risk remains substantial and poorly predictable. TAVR presents a reasonable and more easily accessible alternative and is associated with good short- and mid-term results. In the absence of relevant contraindications, TAVR is presently the preferred treatment option for these patients at our center.

Mid-Term Outcome after Extracorporeal Life Support in Postcardiotomy Cardiogenic Shock: Recovery and Quality of Life.

Background: Extracorporeal life support (ECLS) therapy for refractory postcardiotomy cardiogenic shock (rPCS) is associated with high early mortality rates. This study aimed to identify negative predictors of mid-term survival and to assess health-related quality of life (HRQoL) and recovery of the survivors. Methods: Between 2017 and 2020, 142 consecutive patients received ECLS therapy following cardiac surgery. The median age was 66.0 [57.0-73.0] years, 67.6% were male and the median EuroSCORE II was 10.5% [4.2-21.3]. In 48 patients, HRQoL was examined using the 36-Item Short Form Survey (SF-36) and the modified Rankin-Scale (mRS) at a median follow-up time of 2.2 [1.9-3.2] years. Results: Estimated survival rates at 3, 12, 24 and 36 months were 47%, 46%, 43% and 43% (SE: 4%). Multivariable Cox Proportional Hazard regression analysis revealed preoperative EuroSCORE II (p = 0.013), impaired renal function (p = 0.010), cardiopulmonary bypass duration (p = 0.015) and pre-ECLS lactate levels (p = 0.004) as independent predictors of mid-term mortality. At the time of follow-up, 83.3% of the survivors were free of moderate to severe disability (mRS < 3). SF-36 analysis showed a physical component summary of 45.5 ± 10.2 and a mental component summary of 50.6 ± 12.5. Conclusions: Considering the disease to be treated, ECLS for rPCS is associated with acceptable mid-term survival, health-related quality of life and functional status. Preoperative EuroSCORE II, impaired renal function, cardiopulmonary bypass duration and lactate levels prior to ECLS implantation were identified as negative predictors and should be included in the decision-making process.

Indocyanine green clearance predicts outcome in patients undergoing transcatheter valve intervention for severe atrio-ventricular valve regurgitation.

OBJECTIVES: Severe mitral regurgitation (MR) and tricuspid regurgitation (TR) aggravate haemodynamic stress leading to congestive heart failure with impaired hepatic function, also known as cardiohepatic syndrome (CHS). Current perioperative risk calculators do not sufficiently consider CHS and serum liver function parameters lack sensitivity to diagnose CHS. Indocyanine green and its elimination (measured by the LIMON® test) represent a dynamic and non-invasive test which correlates with the hepatic function. Nevertheless, its utility in the setting of transcatheter valve repair/replacement (TVR) to predict CHS and outcome remains unknown. METHODS: We analysed liver function and outcomes of patients undergoing TVR for MR or TR between August 2020 and May 2021 at the Munich University Hospital. RESULTS: Out of a total of 44 patients treated at the University Hospital of Munich, 21 (48%) were treated for severe MR, 20 (46%) for severe TR and 3 (7%) for both diseases. Procedural success defined as MR/TR ≤2+ was 94% among MR patients and 92% among TR patients. While classical serum liver function parameters did not change after TVR, there was a significant improvement in liver function as assessed by the LIMON® test (P ≤ 0.001). Patients with baseline indocyanine green plasma disappearance rate <12.95%/min showed significantly increased 1-year mortality (hazard ratio: 1.54, 95% confidence interval: 1.05-2.25, P = 0.027) and lower New York Hear Association class improvement (P = 0.05). CONCLUSIONS: Especially in the context of the recently stressed importance of a careful patient selection prior to the interdisciplinary treatment of valvular heart disease, the LIMON® test may provide further real-time information on the patients' cardiohepatic injury and prognosis.

Suture-based vs. pure plug-based vascular closure devices for VA-ECMO decannulation-A retrospective observational study.

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a valuable treatment option for patients in cardiogenic shock, but complications during decannulation may worsen the overall outcome. Therefore, the aim of this study was to compare the efficacy and safety of suture-based to pure plug-based vascular closure devices for VA-ECMO decannulation. Methods: In this retrospective study, the procedural outcome of 33 patients with suture-based Perclose ProGlide closure devices was compared to 38 patients with MANTA plug-based closure devices. Results: Rate of technically correct placement of closure devices was 88% in the suture-based group and 97% in the plug-based group (p = 0.27). There was a significant reduction of severe bleeding events during VA-ECMO decannulation in plug-based versus suture-based systems (3% vs. 21%, p = 0.04). Ischemic complications occurred in 6% with suture-based and 5% with plug-based device (p = 1.00). Pseudoaneurysm formation was detected in 3% in both groups (p = 1.00). No switch to vascular surgery due to bleeding after decannulation was necessary in both groups. Conclusion: Based on our retrospective analysis, we propose that plug-based vascular closure should be the preferred option for VA-ECMO decannulation. This hypothesis should be further tested in a randomized trial.

Quantification of physical activity with prospective activity tracking after transfemoral aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a well-established, safe and effective therapy for severe symptomatic aortic stenosis (AS). The aim of this study was to objectively quantify improvement of physical activity after TAVR, with consideration of different low-gradient AS subtypes. METHODS AND RESULTS: All patients undergoing TAVR for severe AS were screened. Participants received a wearable activity tracker (Fitbit®) at hospital discharge following TAVR and 6 months thereafter. The difference of median daily steps was defined as surrogate outcome for physical activity. For analysis, patients were grouped into high-gradient (HG) AS (dPmean ≥40 mmHg), classical low-flow low-gradient (LFLG) AS (dPmean <40 mmHg, EF <50%), paradoxical LFLG-AS (dPmean <40 mmHg, EF ≥50%, SVi ≤35 ml/m2) and normal-flow low-gradient (NFLG) AS (dPmean <40 mmHg, EF ≥50%, SVi >35 ml/m2) according to mean transvalvular pressure gradient (dPmean), stroke volume index (SVi) and left-ventricular ejection fraction (LVEF). RESULTS AND CONCLUSIONS: The analysis is based on 230 patients. The median daily step count was 4409 [IQR 2581-7487] after hospital discharge and 5326 [IQR 3045-8668] 6 months thereafter. Median difference of daily steps was ∆529 [IQR -702-2152]). Patients with HG-AS and paradoxical LFLG-AS showed a significant improvement of daily steps (∆951 [IQR -378-2323], p <0.001 and (∆1392 [IQR -609-4444], p = 0.02, respectively). Patients with classical LFLG-AS showed no statistically relevant improvement of daily steps (∆192 [IQR -687-770], p = 0.79). Patients with NFLG-AS showed a numerical decline in daily steps without statistical significance (∆-300 [IQR -1334-1406], p = 0.67). This first prospective study of this sample size shows significant improvement of physical activity after TAVR with an objective and reproducible method. This was mainly driven by an improvement in patients with HG-AS and paradoxical LFLG-AS.

TAVI for patients with normal-flow low-gradient compared to high-gradient aortic stenosis.

BACKGROUND: Normal-flow (stroke volume index, SVi >35 ml/m2) low-gradient (dPmean <40 mmHg) aortic stenosis (NFLG-AS) is subject of scientific debate. Guidelines fail to give conclusive treatment recommendations. We hypothesized that NFLG patients are heterogenous, containing a subgroup similar to high-gradient aortic stenosis patients (dPmean ≥40 mmHg, HG-AS) concerning characteristics and outcomes. METHODS: 2326 patients undergoing transcatheter aortic valve replacement (TAVI) at our centre between 2013 and 2019 were analysed. 386 patients fulfilled criteria of NFLG-AS. Their median dPmean was 33 mmHg, which was used for grouping (204 patients with higher gradient NFLG-AS, 186 patients with lower gradient NFLG-AS). They were compared to 956 HG-AS patients. RESULTS: Characteristics of lower gradient NFLG-AS patients differed from HG-AS patients in many aspects while higher gradient NFLG-AS and HG-AS patients were mostly similar, underscored by higher Society of Thoracic Surgeons scores in lower gradient NFLG-AS (lower gradient NFLG-AS, 3.9, HG-AS, 3.0, p = 0.03, higher gradient NFLG-AS, 3.0, p = 0.04). Procedural complications were comparable. Estimated 3-year all-cause mortality was higher in lower gradient NFLG-AS compared to HG-AS patients (hazard ratio 1.7, p < 0.01), whereas mortality of higher gradient NFLG-AS was similar to HG-AS patients (hazard ratio 1.2, p = 0.31). Cardiovascular mortality was highest among lower gradient NFLG-AS patients (21.6% vs. higher gradient NFLG-AS, 15.4%, vs. HG-AS, 11.1%, p < 0.01). CONCLUSIONS: NFLG-AS patients are indeed heterogenous. NFLG-AS patients with higher gradients resemble HG-AS patients in clinical characteristics and outcomes and should not be treated differently. Lower gradient NFLG-AS patients have increased long-term mortality and the use of TAVI requires careful consideration.

Dual ProGlide versus ProGlide and FemoSeal for vascular access haemostasis after transcatheter aortic valve implantation.

BACKGROUND: Large-bore arteriotomy for transcatheter aortic valve implantation (TAVI) requires percutaneous vascular closure devices, but real-world data comparing different closure strategies are limited. AIMS: We sought to compare a dual ProGlide strategy vs a combination of one ProGlide and one FemoSeal for vascular closure after TAVI. METHODS: We retrospectively analysed 874 propensity score-matched patients undergoing TAVI at the Munich University Hospital from August 2018 to October 2020. From August 2018 to August 2019, a dual ProGlide strategy was used for vascular closure. From October 2019 to October 2020, a combination of one ProGlide and one FemoSeal was used. The primary endpoint was defined as access-related major vascular complications or bleeding ≥Type 2 according to Valve Academic Research Consortium 3 criteria. RESULTS: Patients in the dual ProGlide group (n=437) had a higher incidence of the primary endpoint than patients treated with one ProGlide and one FemoSeal (n=437; 11.4% vs 3.0%; p<0.001). Furthermore, they had a higher rate of closure device failure (2.7% vs 0.9%; p=0.044) and more often required unplanned surgery or endovascular treatment (3.9% vs 0.9%; p=0.004). The incidence of death did not differ significantly between groups (3.4% vs 1.6%; p=0.08). CONCLUSIONS: A combined ProGlide and FemoSeal strategy might have the potential to reduce access-related vascular complications following TAVI.

Manual Compression versus Suture-Mediated Closure Device Technique for VA-ECMO Decannulation.

Background: The impact of devices for vessel closure on the safety and efficacy of cannula removal in VA-ECMO patients is unknown. Methods: We retrospectively analyzed 180 consecutive patients weaned from VA-ECMO after cardiac arrest or cardiogenic shock from January 2012 to June 2020. In the first period (historical technique group), from January 2012 to December 2018, primary decannulation strategy was manual compression. In the second period (current technique group), from January 2019 to June 2020, decannulation was performed either by a conventional approach with manual compression or by a suture-mediated closure device technique. Results: A femoral compression system was necessary in 71% of patients in the historical group compared to 39% in the current technique group (p < 0.01). Vascular surgery was performed in 12% in the historical cohort and 2% in the current technique cohort, which indicated a clear trend, albeit it did not reach significance (p = 0.07). Conclusion: We illustrated that a suture-mediated closure device technique for VA-ECMO decannulation was feasible, safe, and may have reduced the need of surgical interventions compared to manual compression alone.

TAVI in patients with low-flow low-gradient aortic stenosis-short-term and long-term outcomes.

OBJECTIVES: The study objective was to characterize different groups of low-flow low-gradient (LFLG) aortic stenosis (AS) and determine short-term outcomes and long-term mortality according to Valve Academic Research Consortium-3 (VARC-3) endpoint definitions. BACKGROUND: Characteristics and outcomes of patients with LFLG AS undergoing transcatheter aortic valve implantation (TAVI) are poorly understood. METHODS: All patients undergoing TAVI at our center between 2013 and 2019 were screened. Patients were divided into three groups according to mean pressure gradient (dPmean), ejection fraction (LVEF), and stroke volume index (SVi): high gradient (HG) AS (dPmean ≥ 40 mmHg), classical LFLG (cLFLG) AS (dPmean < 40 mmHg, LVEF < 50%), and paradoxical LFLG (pLFLG) AS (dPmean < 40 mmHg, LVEF ≥ 50%, SVi ≤ 35 ml/m2). RESULTS: We included 1776 patients (956 HG, 447 cLFLG, and 373 pLFLG patients). Most baseline characteristics differed significantly. Median Society of Thoracic Surgeons (STS) score was highest in cLFLG, followed by pLFLG and HG patients (5.0, 3.9 and 3.0, respectively, p < 0.01). Compared to HG patients, odds ratios for the short-term VARC-3 composite endpoints, technical failure (cLFLG, 0.76 [95% confidence interval, 0.40-1.36], pLFLG, 1.37 [0.79-2.31]) and device failure (cLFLG, 1.06 [0.74-1.49], pLFLG, 0.97 [0.66-1.41]) were similar, without relevant differences within LFLG patients. NYHA classes improved equally in all groups. Compared to HG, LFLG patients had a higher 3-year all-cause mortality (STS score-adjusted hazard ratios, cLFLG 2.16 [1.77-2.64], pLFLG 1.53 [1.22-193]), as well as cardiovascular mortality (cLFLG, 2.88 [2.15-3.84], pLFLG, 2.08 [1.50-2.87]). CONCLUSIONS: While 3-year mortality remains high after TAVI in LFLG compared to HG patients, symptoms improve in all subsets after TAVI.

Hybrid Surgery for Severe Mitral Valve Calcification: Limitations and Caveats for an Open Transcatheter Approach.

Background and Objectives: Mitral stenosis with extensive mitral annular calcification (MAC) remains surgically challenging in respect to clinical outcome. Prolonged surgery time with imminent ventricular rupture and systolic anterior motion can be considered as a complex of causal factors. The aim of our alternative hybrid approach was to reduce the risk of annual rupture and paravalvular leaks and to avoid obstruction of the outflow tract. A review of the current literature was also carried out. Materials and Methods: Six female patients (mean age 76 ± 9 years) with severe mitral valve stenosis and severely calcified annulus underwent an open implantation of an Edwards Sapien 3 prosthesis on cardiopulmonary bypass. Our hybrid approach involved resection of the anterior mitral leaflet, placement of anchor sutures and the deployment of a balloon expanded prosthesis under visual control. Concomitant procedures were carried out in three patients. Results: The mean duration of cross-clamping was 95 ± 31 min and cardiopulmonary bypass was 137 ± 60 min. The perioperative TEE showed in three patients an inconspicuous, heart valve-typical gradient on all implanted prostheses and a clinically irrelevant paravalvular leakage occurred in the anterior annulus. In the left ventricular outflow tract, mild to moderately elevated gradients were recorded. No adverse cerebrovascular events and pacemaker implantations were observed. All but one patient survived to discharge. Survival at one year was 83.3%. Conclusions: This "off label" implantation of the Edwards Sapien 3 prosthesis may be considered as a suitable bail-out approach for patients at high-risk for mitral valve surgery or deemed inoperable due to extensive MAC.

ADP-induced platelet reactivity and bleeding events in patients with acute myocardial infarction complicated by cardiogenic shock.

While previous reports showed ADP-induced platelet reactivity to be an independent predictor of bleeding after PCI in stable patients, this has never been investigated in patients with cardiogenic shock. The association of bleeding events with respect to ADP-induced platelet aggregation was investigated in patients undergoing primary PCI for acute myocardial infarction complicated by cardiogenic shock and with available on-treatment ADP-induced platelet aggregation measurements. Out of 233 patients, 74 suffered from a severe BARC3 or higher bleed. ADP-induced platelet aggregation was significantly lower in patients with BARC≥3 bleedings (p < .001). Multivariate analysis identified on-treatment ADP-induced platelet aggregation as an independent risk factor for bleeding (HR = 0.968 per AU). An optimal cutoff value of <12 AU for ADP-induced platelet aggregation to predict BARC≥3 bleedings was identified via ROC analysis. Moreover, the use of VA-ECMO (HR 1.972) or coaxial left ventricular pump (HR 2.593), first lactate (HR 1.093 per mmol/l) and thrombocyte count (HR 0.994 per G/l) were independent predictors of BARC≥3 bleedings. In conclusion, lower on-treatment ADP-induced platelet aggregation was independently associated with severe bleeding events in patients with AMI-CS. The value of platelet function testing for bleeding risk prediction and guidance of anti-thrombotic treatment in cardiogenic shock warrants further investigation.

How exercise can deteriorate the clinical course of an ARVC patient: a case report.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC)/dysplasia is a genetic disease characterized by fibro-adipose degeneration of ventricular myocardium. Initial clinical presentation is variable and ranges from asymptomatic cases to chronic heart failure and sudden cardiac death due to malignant arrhythmias. CASE SUMMARY: Here, a 67-year-old male patient who started extensive physical training upon retirement and presented with ventricular tachycardia and progressive heart failure as a first sign of his disease. Arrhythmogenic right ventricular cardiomyopathy diagnosis was established according to the 2010 modified Task Force Criteria and supported by HRS/EHRA consensus-based genotyping. After initial discharge on optimal medical therapy and prophylactic implantable cardioverter-defibrillator implantation according to his individual ARVC risk score, the patient reported rapid decline in physical capacity on a regular follow-up 4 months later. To better understand the aetiology of his clinical deterioration, we performed stress echocardiography, coronary angiogram, and exercise right heart catheterization, which conclusively suggest impaired left ventricular filling secondary to right ventricular failure as a main cause of global circulatory failure. DISCUSSION: The present case report focuses on relation of physical activity to disease onset and the concomitant advent of symptoms during exercise as well as a structured and guideline-aided diagnostic workup in ARVC and staged treatment options. Continuous ARVC centre-oriented re-assessment and treatment planning including lifestyle intervention, psychological support, medical, surgical, and interventional options are key elements of sustained long-term care for ARVC patients.

Pembrolizumab-induced myocarditis in a patient with malignant mesothelioma: plasma exchange as a successful emerging therapy-case report.

Malignant mesothelioma is an aggressive cancer associated with prior exposure to asbestos and dismal prognosis. Immune checkpoint inhibitor therapy is currently approved by the Food and Drug Administration for pre-treated malignant pleural mesothelioma. We describe a 75-year-old patient with disseminated, progressive malignant mesothelioma receiving 2 cycles of pembrolizumab who presented with generalized muscle weakness, shortness of breath, double vision and ptosis. There was no previous history of cardiovascular disease. The clinical picture, supported by the detection of anti-titin autoantibodies suggested myasthenia gravis (MG). Also, cardiac biomarkers were elevated. Echocardiography showed new severely reduced ejection fraction. A 12-lead resting electrocardiogram (ECG) revealed ST segment elevation in the posterior leads with polymorphic ventricular extrasystoles. Because cardiac catheterization revealed no relevant coronary lesions, immune checkpoint inhibitor-associated myocarditis and MG were suspected. Management and Outcome: The patient was started on steroids. Within a few days of presentation respiratory failure set in and the patient was intubated. Recurrent arrhythmias followed, which were treated by repeated emergency electrical cardioversion. In order to relieve myasthenic symptoms, plasma exchange was initiated and 10 cycles were carried out. This consequently also led to an improvement of myocarditis. Upon discharge, the ejection fraction recovered. The patient recovered and was alive at 1-year follow-up, without relevant limitations to his quality of life. Discussion and Conclusion: The article further discusses the use of plasma exchange for immune checkpoint inhibitor-associated myocarditis based on a review of literature. We conclude that patients showing no improvement after steroid therapy for immune checkpoint inhibitor-related myocarditis should be evaluated for plasma exchange, which appears to be an effective treatment option.

Extracorporeal life support in therapy-refractory cardiocirculatory failure: looking beyond 30 days.

OBJECTIVES: Venoarterial extracorporeal life support (ECLS) has emerged as a potentially life-saving treatment option in therapy-refractory cardiocirculatory failure, but longer-term outcome is poorly defined. Here, we present a comprehensive follow-up analysis covering all major organ systems. METHODS: From February 2012 to December 2016, 180 patients were treated with ECLS for therapy-refractory cardiogenic shock or cardiac arrest. The 30-day survival was 43.9%, and 30-day survivors (n = 79) underwent follow-up analysis with the assessment of medium-term survival, quality of life, neuropsychological, cardiopulmonary and end-organ status. RESULTS: After a median of 1.9 (1.1-3.6) years (182.4 patient years), 45 of the 79 patients (57.0%) were alive, 35.4% had died and 7.6% were lost to follow-up. Follow-up survival estimates were 78.0% at 1, 61.2% at 3 and 55.1% at 5 years. NYHA class at follow-up was ≤II for 83.3%. The median creatinine was 1.1 (1.0-1.4) mg/dl, and the median bilirubin was 0.8 (0.5-1.0) mg/dl. No patient required dialysis. Overall, 94.4% were free from moderate or severe disability, although 11.1% needed care. Full re-integration into social life was reported by 58.3%, and 39.4% were working. Quality of life was favourable for mental components, but a subset showed deficits in physical aspects. While age was the only peri-implantation parameter significantly predicting medium-term survival, adverse events and functional status at discharge or 30 days were strong predictors. CONCLUSIONS: This study demonstrates positive medium-term outcome with high rates of independence in daily life and self-care but a subset of 10-20% suffered from sustained impairments. Our results indicate that peri-implantation parameters lack predictive power but downstream morbidity and functional status at discharge or 30 days can help identify patients at risk for poor recovery.

Smoking and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients: a substudy from the randomized TROPICAL-ACS trial.

AIMS: Prior analyses disclosed variations in antiplatelet drug response and clinical outcomes between smokers and non-smokers, thus the safety and efficacy of any dual antiplatelet therapy (DAPT) de-escalation strategy may differ in relation to smoking status. Hence, we assessed the impact of smoking on clinical outcomes and adenosine diphosphate-induced platelet aggregation following guided de-escalation of DAPT in invasively managed acute coronary syndrome (ACS) patients. METHODS AND RESULTS: The multicentre TROPICAL-ACS trial randomized 2610 biomarker-positive ACS patients 1:1 to standard treatment with prasugrel for 12 months (control group) or a platelet function testing guided de-escalation of DAPT. Current smokers (n = 1182) showed comparable event rates between study groups [6.6% vs. 6.6%; hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.64-1.56, P > 0.99]. In non-smokers (n = 1428), a guided DAPT de-escalation was associated with a lower 1-year incidence of the primary endpoint [cardiovascular death, myocardial infarction, stroke, or bleeding ≥ Grade 2 according to Bleeding Academic Research Consortium (BARC) criteria] compared with control group patients (7.9% vs. 11.0%; HR 0.71, 95% CI 0.50-0.99, P = 0.048). This reduction was mainly driven by a lower rate of BARC ≥ Grade 2 bleedings (5.2% vs. 7.7%; HR 0.68, 95% CI 0.45-1.03, P = 0.066). There was no significant interaction of smoking status with treatment effects of guided DAPT de-escalation (Pint = 0.23). Adenosine diphosphate-induced platelet aggregation values were higher in current smokers [median 28 U, interquartile range (IQR: 20-40)] vs. non-smoker [median 24 U (16-25), P < 0.0001] in the control group and in current smokers [median 42 U, IQR (27-68)] vs. non-smoker [median 37 U, IQR (25-55), P < 0.001] in the monitoring group. CONCLUSION: Guided DAPT de-escalation appears to be equally safe and effective in smokers and non-smokers. Regardless of smoking status and especially for those patients deemed unsuitable for 1 year of potent platelet inhibition this DAPT strategy might be used as an alternative antiplatelet treatment regimen.

Impact of Transcatheter Tricuspid Valve Repair for Severe Tricuspid Regurgitation on Kidney and Liver Function.

OBJECTIVES: This study sought to determine the impact of transcatheter tricuspid edge-to-edge valve repair (TTVR) of severe tricuspid regurgitation (TR) on kidney and liver functions. BACKGROUND: TR leads to impairment in renal and hepatic function, which is associated with worse prognosis. TTVR emerged as a treatment option for patients ineligible for cardiac surgery. However, no study has assessed the impact of TTVR on kidney and liver functions. METHODS: All patients treated with TTVR in our center between March 2016 and June 2018 were included. Kidney and liver functions were compared at baseline, 30 days, and 6 months. RESULTS: Over the study period, 126 patients were treated for TR (59 isolated TTVR and 67 TMTVR). Among them, 110 (87.3%) survived at 6 months. Among survivors, renal function remained stable, including among patients with moderate-to-severe chronic kidney disease (mean glomerular filtration rate 37.5 ml/min/1.73 m2 at baseline vs. 40.1 ml/min/1.73 m2 at 6 months; p = 0.39). Regarding liver function, a significant improvement at 6 months was only observed in the alanine transaminase level in the entire cohort (30.7 U/l vs. 24.9 U/l; p < 0.001). Among patients with abnormal baseline liver function, significant reductions in aspartate transaminase (50.5 U/l to 39.9 U/l; p = 0.02) and bilirubin (1.8 mg/dl to 1.5 mg/dl; p = 0.03) were also observed. CONCLUSIONS: TR reduction by TTVR is associated with an improvement in liver function, mainly among patients with abnormal liver function at baseline, whereas kidney function remained stable. Accordingly, TTVR is an attractive option especially for patients presenting with severe TR and liver dysfunctions, who are at even higher surgical risk compared with patients who still have normal organ functions.

Diurnal Variability of On-Treatment Platelet Reactivity in Clopidogrel versus Prasugrel Treated Acute Coronary Syndrome Patients: A Pre-Specified TROPICAL-ACS Sub-Study.

Long-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2,610 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2,526 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1,265) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5-10 a.m.). In prasugrel-treated patients (n = 1,261), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.

Platelet Reactivity and Early Outcomes after Transfemoral Aortic Valve Implantation.

Beyond thromboembolic events, peri-procedural bleeding remains one of the most frequent complications after transcatheter aortic valve implantation (TAVI). The majority of TAVI patients receive a dual anti-platelet treatment (DAPT) regimen. This analysis from the EVERY-TAVI register database aimed to analyse whether the level of on-treatment adenosine diphosphate-induced platelet reactivity predicts early outcomes at 30 days after TAVI. A total of 146 consecutive TAVI patients on DAPT who underwent platelet function testing with the Multiplate analyser were included here. Definition of bleeding events was done according to the Valve Academic Research Consortium-2 (VARC-2) classification. In our cohort, a status of low platelet reactivity (LPR, ≤ 18 units) was observed in 79 patients (54%), while high platelet reactivity (HPR, ≥ 46 units) was present in 18 patients (12%). At 30-day follow-up, the incidence of VARC-2 bleeds was 45.6% (n = 36) in LPR patients and 23.9% (n = 16) in patients without LPR (hazard ratio [HR] 2.10, 95% confidence interval [CI], 1.17-3.79; p = 0.01). In age-adjusted multivariate analysis, a status of LPR was independently associated with VARC-2 bleeding events (HRadj, 2.06, 95% CI, 1.14-3.71; p = 0.02). HPR was not associated with the 30-day risk of death, stroke, or myocardial infarction (p ≥ 0.43). In summary, presence of LPR was associated with bleeding events in patients undergoing TAVI while presence of HPR was not associated with ischaemic outcomes at 30 days. The value of platelet function testing for bleeding risk prediction and for a possible guidance of anti-thrombotic treatment in the elderly TAVI population warrants further investigation.

Six-month outcome after transcatheter edge-to-edge repair of severe tricuspid regurgitation in patients with heart failure.

AIMS: Severe tricuspid regurgitation (TR) is common in patients with right-sided heart failure (HF) and causes substantial morbidity and mortality. Treatment options beyond medical therapy are limited for high-risk patients. Transcatheter edge-to-edge tricuspid valve (TV) repair showed procedural safety and short-term efficacy. Impact on mid-term outcome is unclear. This dual-centre observational study evaluates the mid-term safety, efficacy and clinical outcome after edge-to-edge TV repair for severe TR in patients with HF. METHODS AND RESULTS: Overall, 50 patients with right-sided HF and severe TR were treated with the transcatheter edge-to-edge repair technique; 14 patients were treated for isolated TR and 36 patients for combined mitral regurgitation (MR) and TR. At 6-month follow-up (available for 98% of patients), a persistent reduction of at least one echocardiographic TR grade was achieved in 90% of patients and New York Heart Association class improved in 79% of patients. The 6-minute walk distance increased by 44% (+84 m, P < 0.001), the median N-terminal pro-B-type natriuretic peptide decreased by 30% (from 3625 to 2526 pg/mL, P = 0.002), and the quality of life score improved by 16% (decrease of 6 points in the Minnesota Living with Heart Failure Questionnaire score, P = 0.056). The improvements were comparable in patients undergoing isolated TR or combined MR and TR treatment. During follow-up, 8 patients died, 14 were hospitalized for worsening of HF, 2 underwent TV surgery, and 2 received a second TV clip procedure. CONCLUSIONS: Transcatheter edge-to-edge TV repair for severe TR is safe and effective in reducing TR. It appears to be associated with improved clinical outcome in the majority of patients.