Region and cell-type resolved quantitative proteomic map of the human heart

The heart is a central human organ and its diseases are the leading cause of death worldwide, but an in-depth knowledge of the identity and quantity of its constituent proteins is still lacking. Here, we determine the healthy human heart proteome by measuring 16 anatomical regions and three major cardiac cell types by high-resolution mass spectrometry-based proteomics. From low microgram sample amounts, we quantify over 10,700 proteins in this high dynamic range tissue. We combine copy numbers per cell with protein organellar assignments to build a model of the heart proteome at the subcellular level. Analysis of cardiac fibroblasts identifies cellular receptors as potential cell surface markers. Application of our heart map to atrial fibrillation reveals individually distinct mitochondrial dysfunctions. The heart map is available at maxqb. biochem. mpg. de as a resource for future analyses of normal heart function and disease

Early and late outcomes after minimally invasive direct coronary artery bypass vs. full sternotomy off-pump coronary artery bypass grafting

ObjectivesMinimally-invasive direct coronary artery bypass (MIDCAB) is a less-invasive alternative to full sternotomy off-pump coronary artery bypass (FS-OPCAB) revascularization of the left anterior descending artery (LAD). Some studies suggested that MIDCAB is associated with a greater risk of graft occlusion and repeat revascularization than FS-OPCAB LIMA-to-LAD grafting. Data comparing MIDCAB to FS-OPCAB with regard to long-term follow-up is scarce. We compared short- and long-term results of MIDCAB vs. FS-OPCAB revascularization over a maximum follow-up period of 10 years.Patients and methodsFrom December 2009 to June 2020, 388 elective patients were included in our retrospective study. 229 underwent MIDCAB, and 159 underwent FS-OPCAB LIMA-to-LAD grafting. Inverse probability of treatment weighting (IPTW) was used to adjust for selection bias and to estimate treatment effects on short- and long-term outcomes. IPTW-adjusted Kaplan–Meier estimates by study group were calculated for all-cause mortality, stroke, the risk of repeat revascularization and myocardial infarction up to a maximum follow-up of 10 years.ResultsMIDCAB patients had less rethoracotomies (n = 13/3.6% vs. n = 30/8.0%, p = 0.012), fewer transfusions (0.93 units ± 1.83 vs. 1.61 units ± 2.52, p < 0.001), shorter mechanical ventilation time (7.6 ± 4.7 h vs. 12.1 ± 26.4 h, p = 0.005), and needed less hemofiltration (n = 0/0% vs. n = 8/2.4%, p = 0.004). Thirty-day mortality did not differ significantly between the two groups (n = 0/0% vs. n = 3/0.8%, p = 0.25). Long-term outcomes did not differ significantly between study groups. In the FS-OPCAB group, the probability of survival at 1, 5, and 10 years was 98.4%, 87.8%, and 71.7%, respectively. In the MIDCAB group, the corresponding values were 98.4%, 87.7%, and 68.7%, respectively (RR1.24, CI0.87–1.86, p = 0.7). In the FS group, the freedom from stroke at 1, 5, and 10 years was 97.0%, 93.0%, and 93.0%, respectively. In the MIDCAB group, the corresponding values were 98.5%, 96.9%, and 94.3%, respectively (RR0.52, CI0.25–1.09, p = 0.06). Freedom from repeat revascularization at 1, 5, and 10 years in the FS-OPCAB group was 92.2%, 84.7%, and 79.5%, respectively. In the MIDCAB group, the corresponding values were 94.8%, 90.2%, and 81.7%, respectively (RR0.73, CI0.47–1.16, p = 0.22).ConclusionMIDCAB is a safe and efficacious technique and offers comparable long-term results regarding mortality, stroke, repeat revascularization, and freedom from myocardial infarction when compared to FS-OPCAB

The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3

Brodehl A, Hain C, Flottmann F, et al. The Desmin Mutation DES-c.735G>C Causes Severe Restrictive Cardiomyopathy by Inducing In-Frame Skipping of Exon-3. Biomedicines. 2021;9(10): 1400.Currently, little is known about the genetic background of restrictive cardiomyopathy (RCM). Herein, we screened an index patient with RCM in combination with atrial fibrillation using a next generation sequencing (NGS) approach and identified the heterozygous mutation DES-c.735G>C. As DES-c.735G>C affects the last base pair of exon-3, it is unknown whether putative missense or splice site mutations are caused. Therefore, we applied nanopore amplicon sequencing revealing the expression of a transcript without exon-3 in the explanted myocardial tissue of the index patient. Western blot analysis verified this finding at the protein level. In addition, we performed cell culture experiments revealing an abnormal cytoplasmic aggregation of the truncated desmin form (p.D214-E245del) but not of the missense variant (p.E245D). In conclusion, we show that DES-c.735G>C causes a splicing defect leading to exon-3 skipping of the DES gene. DES-c.735G>C can be classified as a pathogenic mutation associated with RCM and atrial fibrillation. In the future, this finding might have relevance for the genetic understanding of similar cases

The ROMA trial: 7 years of trial activities and the development of the ROMA trial network

INTRODUCTIONThe Randomized Comparison of the Clinical Outcomes of Single versus Multiple Arterial Grafts (ROMA) trial (NCT03217006) [1] is the largest randomized trial testing the hypothesis that multiple arterial grafting (MAG) provides superior clinical outcomes compared to single arterial grafting (SAG) in patients undergoing coronary artery bypass surgery (CABG).Trial activities started in January 2017, the first patient was enrolled in January 2018, and the last one (# 4375) was enrolled on 14 April 2023.Here, we summarize the first 7 years of ROMA activities, with particular focus on those aspects that may potentially be relevant for trialists interested in designing or implementing other large cardiac surgery trials. As the trial is ongoing and the primary analysis has not been performed yet, no outcomes or individual patient data are provided

The ROMA trial: 7 years of trial activities and the development of the ROMA trial network

INTRODUCTIONThe Randomized Comparison of the Clinical Outcomes of Single versus Multiple Arterial Grafts (ROMA) trial (NCT03217006) [1] is the largest randomized trial testing the hypothesis that multiple arterial grafting (MAG) provides superior clinical outcomes compared to single arterial grafting (SAG) in patients undergoing coronary artery bypass surgery (CABG).Trial activities started in January 2017, the first patient was enrolled in January 2018, and the last one (# 4375) was enrolled on 14 April 2023.Here, we summarize the first 7 years of ROMA activities, with particular focus on those aspects that may potentially be relevant for trialists interested in designing or implementing other large cardiac surgery trials. As the trial is ongoing and the primary analysis has not been performed yet, no outcomes or individual patient data are provided

Transcatheter Aortic Valve Replacement Outcomes in Patients With Native vs Transplanted Kidneys: Data From an International Multicenter Registry

Background: Chronic kidney disease (CKD) has a negative impact on outcomes after transcatheter aortic valve replacement (TAVR). Data on outcomes in renal transplant recipients (RTRs) undergoing TAVR are scarce. We compared the outcomes in RTRs undergoing TAVR with matched patients who have native kidneys and similar kidney function.Methods: This retrospective cohort study used data from 16 TAVR centres (13,941 patients). The study cohort included 216 patients (72 RTRs and 144 matched controls).Results: The mean estimated glomerular filtration rate (eGFR) was 39.2 +/- 23.6 vs 44.5 +/- 23.6 mL/min for RTRs and control patients (P = 0.149), with a similar CKD stage distribution. After TAVR, the eGFR declined among RTRs but remained stable for up to 1 year in controls (P = 0.021). Long-term hemodialysis was required in 19 (26.4%) RTRs and 20 (13.8%) controls (hazard ratio [HR] = 2.09 95% confidence interval [CI], 1.03-3.86; P = 0.039) and was most often initiated during the periprocedural period (14 RTRs vs 16 controls; P = 0.039). After a median follow-up of 2.3 years, risk of death (29.2% vs 31.9%) and death/hemodialysis (40.3% vs 36.8%) was similar between the groups. The contrast volume/eGFR ratio was the strongest predictor of hemodialysis initiation (odds ratio [OR] = 1.64; 95% CI, 1.36-1.97 per 1 unit increase; P < 0.001), with a greater effect among RTRs than controls (P for interaction = 0.022).Conclusion: s: TAVR appears safe in RTRs with mortality rates similar to matched patients with native kidneys. However, RTRs carry an increased risk of progressive renal impairment and need for hemodialysis initiation after TAVR. Our data highlight the importance of minimizing contrast load during TAVR, particularly in RTRs

Transcatheter Aortic Valve Replacement in Pure Native Aortic Valve Regurgitation

Background Limited data exist about safety and efficacy of transcatheter aortic valve replacement (TAVR) in patients with pure native aortic regurgitation (AR). Objectives This study sought to compare the outcomes of TAVR with early- and new-generation devices in symptomatic patients with pure native AR. Methods From the pure native AR TAVR multicenter registry, procedural and clinical outcomes were assessed according to VARC-2 criteria and compared between early- and new-generation devices. Results A total of 331 patients with a mean STS score of 6.7 ± 6.7 underwent TAVR. The early- and new-generation devices were used in 119 patients (36.0%) and 212 patients (64.0%), respectively. STS score tended to be lower in the new-generation device group (6.2 ± 6.7 vs. 7.6 ± 6.7; p = 0.08), but transfemoral access was more frequently used in the early-generation device group (87.4% vs. 60.8%; p < 0.001). Compared with the early-generation devices, the new-generation devices were associated with a significantly higher device success rate (81.1% vs. 61.3%; p < 0.001) due to lower rates of second valve implantation (12.7% vs. 24.4%; p = 0.007) and post-procedural AR â\u89¥ moderate (4.2% vs. 18.8%; p < 0.001). There were no significant differences in major 30-day endpoints between the 2 groups. The cumulative rates of all-cause and cardiovascular death at 1-year follow-up were 24.1% and 15.6%, respectively. The 1-year all-cause mortality rate was significantly higher in the patients with post-procedural AR â\u89¥ moderate compared with those with post-procedural AR â\u89¤ mild (46.1% vs. 21.8%; log-rank p = 0.001). On multivariable analysis, post-procedural AR â\u89¥ moderate was independently associated with 1-year all-cause mortality (hazard ratio: 2.85; 95% confidence interval: 1.52 to 5.35; p = 0.001). Conclusions Compared with the early-generation devices, TAVR using the new-generation devices was associated with improved procedural outcomes in treating patients with pure native AR. In patients with pure native AR, significant post-procedural AR was independently associated with increased mortality