The autonomic nerves around the vein of Marshall: a postmortem study with clinical implications.

This study aims to analyze the vein of Marshall (VOM) in human autopsy hearts and its correlation with clinical data to elucidate the morphological substrates of atrial fibrillation (AF) and other cardiac diseases. Twenty-three adult autopsy hearts were studied, assessing autonomic nerves by immunohistochemistry with tyrosine hydroxylase (sympathetic nerves), choline acetyltransferase (parasympathetic nerves), growth-associated protein 43 (neural growth), and S100 (general neural marker) antibodies. Interstitial fibrosis was assessed by Masson trichrome staining. Measurements were conducted via morphometric software. The results were correlated with clinical data. Sympathetic innervation was abundant in all VOM-adjacent regions. Subjects with a history of AF, cardiovascular cause of death, and histologically verified myocardial infarction had increased sympathetic innervation and neural growth around the VOM at the mitral isthmus. Interstitial fibrosis increased with age and heart weight was associated with AF and cardiovascular cause of death. This study increases our understanding of the cardiac autonomic innervation in the VOM area in various diseases, offering implications for the development of new therapeutic approaches targeting the autonomic nervous system.

Histopathology reveals concealed aortic valve inflammation.

BACKGROUND: The extent of aortic valve inflammation in patients undergoing aortic valve replacement (AVR) is unsettled. The significance of aortic valve histopathology in patients undergoing AVR is undetermined. METHODS: A total of 145 resected aortic valves of consecutive patients undergoing surgery for a local aortic valve disease with or without ascending aorta were investigated for histopathology. The extent of inflammation and degeneration were investigated. Unadjusted survival was evaluated by Kaplan-Meier analysis. Median follow-up was 2.7 years (interquartile range 1.5-3.9). RESULTS: Mean patient age was 69 (SD 11) years. Though endocarditis was apparent in only six patients preoperatively, severe aortic valve inflammation was diagnosed histologically in 32 patients of whom 12 patients had acute, subacute or chronic endocarditis. Despite complete aortic valve resection, survival was decreased in patients with severe aortic valve inflammation as opposed to those without (log rank, P = 0.044), even after exclusion of patients with endocarditis, emergency and aortic surgery. CONCLUSIONS: Aortic valve tissue analysis reveals severe inflammation that may require postoperative treatment. The association of severe but local aortic valve inflammation with patient outcome after aortic valve surgery merits further investigation.

Aortic elastic fiber degeneration during acute type a aortic dissection and reverse aortic remodeling.

BACKGROUND: Progression of proximal or distal aortic dilatation is defined as reverse aortic remodeling after surgery for acute type A aortic dissection (ATAAD) that may be dependent on aortic wall degeneration. METHODS: We investigated whether aortic wall degeneration is associated with reverse aortic remodeling leading to aortic reoperation after surgery for ATAAD. Altogether, 141 consecutive patients undergoing surgery for ATAAD at Tampere were evaluated. The resected ascending aortic wall at surgery was processed for 42 degenerative, atherosclerotic and inflammatory histological variables. Patients undergoing aortic reoperations (Redos) were compared with those without aortic reoperations (Controls) during a mean 4.9-year follow-up. RESULTS: Redos were younger than Controls (56 and 66 years, respectively, P < 0.001), and had less frequently previous cardiac surgery prior to ATAAD. Initial surgery encompassed replacement of the ascending aorta in the majority. There were 21 Redos in which one patient died during follow-up as compared with 51 deaths in Controls (log Rank P = 0.002). Histology of the aortic wall revealed increased elastic fiber fragmentation, loss, and disorganization in Redos as compared with Controls (2.1 ± 0.5 vs. 1.9 ± 0.5, Point score unit (PSU), P = 0.043 and 1.7 ± 0.8 vs. 1.2 ± 0.8, PSU, P = 0.016, respectively). Moderate atherosclerosis occurred less often in Redos vs. Controls (9.5% vs. 33%, PSU, P = 0.037, respectively). CONCLUSIONS: According to this exploratory study, histopathology reveals distinctive aortic wall degeneration during ATAAD. Reverse aortic remodeling after ATAAD is associated with the presence of ascending aortic wall elastic fiber fragmentation, loss and disorganization during ATAAD.

Detailed study of collagen, vasculature, and innervation in the human cardiac conduction system.

BACKGROUND: The cardiac conduction system (CCS) creates and propagates electrical signals generating the heartbeat. This study aimed to assess the collagen content, vasculature, and innervation in the human sinoatrial and atrioventricular CCS, and surrounding tissue. MATERIALS AND METHODS: Ten sinoatrial and 17 atrioventricular CCS samples were collected from 17 adult human autopsied hearts. Masson trichrome stain was used to examine collagen, cardiomyocytes, and fat proportions. Immunohistochemically, vessels and lymphatics were studied by CD31 (pan-endothelial marker) and D2-40 (lymphatic endothelium marker) antibodies. General nerve densities were assessed by S100, while sympathetic nerves were studied using tyrosine hydroxylase, parasympathetic nerves with choline acetyltransferase, and GAP43 (neural growth marker) antibodies looked at these components. All components were quantified with QuPath software (Queens University, Belfast, Northern Ireland). RESULTS: Interstitial collagen was more than two times higher in the sinoatrial vs. atrioventricular CCS (55% vs. 22%). The fat content was 6.3% in the sinoatrial CCS and 6.5% in the atrioventricular CCS. The lymphatic vessel density was increased in the sinoatrial and atrioventricular CCS compared to the surrounding tissue and was lower in the sinoatrial vs. atrioventricular CCS (P=.043). The overall vasculature density did not differ between the SA and AV CCS. The overall innervation and neural growth densities were significantly increased in the CCS compared to the surrounding tissue. The overall innervation was higher in the atrial vs. ventricular CCS (P=.018). The neural growth was higher in the atrial vs. ventricular CCS (P=.018). The sympathetic neural supply was dominant in all the studied regions with the highest density in the sinoatrial CCS. CONCLUSIONS: Our results provide new insights into the unique morphology of the human CCS collagen, fat, vasculature, and innervation. A deeper understanding of the CCS anatomical components and morphologic substrates' role will help in elucidating the causes of cardiac arrhythmias and provide a basis for further therapeutic interventions.

Rapid-deployment aortic valve replacement during challenging aortic valve reoperation: a case report.

A previously implanted stenotic aortic valve bioprosthesis with stenotic coronary ostia and intramyocardial calcium was surgically debrided resulting in disruption of the left outflow track. A rapid-deployment aortic valve bioprosthesis was implanted to cover the remnant aortic valve annulus, ensure open coronary ostia, and secure a well-functioning aortic valve bioprosthesis with low postoperative gradient.

Type A Aortic Dissection Repair in Patients With Prior Cardiac Surgery.

BACKGROUND: Emergency surgery for acute type A aortic dissection in patients with previous cardiac surgery is controversial. This study aimed to evaluate the association between previous cardiac surgery and outcomes after surgery for acute type A aortic dissection, to appreciate whether emergency surgery can be offered with acceptable risks. METHODS: All patients operated on for acute type A aortic dissection between 2005 and 2014 from the Nordic Consortium for Acute Type A Aortic Dissection database were eligible. Patients with previous cardiac surgery were compared with patients without previous cardiac surgery. Univariable and multivariable statistical analyses were performed to identify predictors of 30-day mortality and early major adverse events (a secondary composite endpoint comprising 30-day mortality, perioperative stroke, postoperative cardiac arrest, or de novo dialysis). RESULTS: In all, 1159 patients were included, 40 (3.5%) with previous cardiac surgery. Patients with previous cardiac surgery had higher 30-day mortality (30% vs 17.8%, P = .049), worse medium-term survival (51.7% vs 71.2% at 5 years, log rank P = .020), and higher unadjusted prevalence of major adverse events (52.5% vs 35.7%, P = .030). In multivariable analysis, previous cardiac surgery was not associated with 30-day mortality (odds ratio 0.78; 95% CI, 0.30-2.07; P = .624) or major adverse events (odds ratio 1.07; 95% CI, 0.45-2.55, P = .879). CONCLUSIONS: Major adverse events after surgery for acute type A aortic dissection were more frequent in patients with previous cardiac surgery. Previous cardiac surgery itself was not an independent predictor for adverse events, although the small sample size precludes definite conclusions. Previous cardiac surgery should not deter from emergency surgery.

Temperature effects on incidence of surgery for acute type A aortic dissection in the Nordics.

We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (≤-5°C) and hot temperatures (≥21°C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.

Myocardial interaction of apixaban after experimental acute volume overload.

OBJECTIVE: Acute volume overload (AVO) induces early ischemia-like changes in intramyocardial arteries. We investigated whether the Factor Xa (FXa) inhibitor apixaban interacts with the myocardium early after AVO. METHODS: Fifty-five syngeneic Fisher rats underwent surgical abdominal aortocaval fistula to induce AVO. Among them, 17 rats were treated with apixaban (10 mg/kg/day). The myocardial outcome was studied using histological analysis and by measuring atrial natriuretic peptide (ANP) and matrix metalloprotease 9 (MMP9) gene expression. RESULTS: After 3 days, the total number of intramyocardial arteries was significantly increased in the AVO+apixaban (AVO+A) group compared with that in the AVO group (12.0 ± 1.2 and 10.2 ± 1.5, point score units, respectively). In the AVO+A group, there were significantly more edematous nuclei in myocardial arteries in the right and left ventricle compared with that in the AVO group. ANP and MMP9 expression levels continued to increase significantly in the AVO+A group compared with those in the AVO group. CONCLUSION: Apixaban interacts with intramyocardial arteries in the left and right ventricles after AVO and ANP and MMP9 expression levels increased. Thus, the myocardial effect of Factor Xa inhibition needs to be monitored after AVO.

Impact of national holidays and weekends on incidence of acute type A aortic dissection repair.

Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54-0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68-0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.

Human Pulmonary Vein Myocardial Sleeve Autonomic Neural Density and Cardiovascular Mortality.

Myocardial sleeves around pulmonary veins (PVs) are highly innervated structures with heterogeneous morphological and electrophysiological characteristics. Autonomic nerve dysfunction in the myocardium may be associated with an increased risk of cardiovascular morbidity and mortality. This article studied autonomic neural remodeling in myocardial sleeves around PVs and atrial-PV ostia with immunohistochemical and morphometric methods with clinicopathological correlations. PVs were collected from 37 and atrial-PV ostia from 17 human autopsy hearts. Immunohistochemical analysis was performed using antibodies against tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), and growth-associated protein 43 (GAP43). In the PV cohort, subjects with immediate cardiovascular cause of death had significantly decreased sympathetic nerve density in fibro-fatty tissue vs those with non-cardiovascular cause of death (1624.53 vs 2522.05 µm2/mm2, p=0.038). In the atrial-PV ostia cohort, parasympathetic nerve density in myocardial sleeves was significantly increased in subjects with underlying cardiovascular cause of death (19.48 µm2/mm2) than subjects with underlying non-cardiovascular cause of death with no parasympathetic nerves detected (p=0.034). Neural growth regionally varied in sympathetic nerves and was present in most of the parasympathetic nerves. Heterogeneous autonomic nerve distribution and growth around PVs and atrial-PV ostia might play a role in cardiovascular morbidity and mortality. No association in nerve density was found with atrial fibrillation.

Is mood associated with perception of recovery? Preoperative depression versus postoperative delirium after cardiac surgery.

The author alone is responsible for the Invited Commentary, which does not necessarily reflect the policy of the Journal.

Early reversibility of histological changes after experimental acute cardiac volume-overload.

Unloading the heart may aid recovery after acute cardiac volume-overload (AVO). We experimentally investigated whether unloading the heart after AVO by heterotopic transplantation histologically impacts myocardial outcome. Thirty-two syngeneic Fisher 344 rats underwent surgery for abdominal arterial-venous fistula to induce AVO. Seven hearts were heterotopically transplanted one day after AVO to simulate a non-working state of the left ventricle (AVO+Tx). In addition, six rats without AVO or surgery (Normal) and five rats with sham surgery (Sham) served as controls. Myocardial outcome was studied using histology and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis for hypoxia inducible factor 1alpha (HIF1α), inducible nitric oxide synthase (iNOS), E-selectin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), vascular endothelial growth factor alpha (VEGFα), matrix metalloprotease 9 (MMP9), chitinase-3-like protein (YKL-40) and transforming growth factor beta (TGFß). Relative ischemia of the right ventricle and septal intramyocardial arteries was decreased in AVO+Tx as compared with AVO (0.04±0.01 vs. 0.09±0.02, PSU, P=0.040 and 0.04±0.01 vs. 0.16±0.02, PSU, P=0.008, respectively). Quantitative RT-PCR showed an increase in the expression of iNOS, YKL-40 and VEGFα, and decrease in ANP in AVO+Tx as compared with AVO (5.78±1.23 vs. 2.46±0.81, P=0.039, 22.39±5.22 vs. 10.79±1.70, P=0.039 and 1.15±0.22 vs. 0.60±0.08, P=0.030, and 1.32±0.16 vs. 2.85±0.70, P=0.039, respectively). Unloading the heart by heterotopic transplantation induces early ischemic recovery of intramyocardial arteries after AVO. A non-working state reverses acute ischemic myocardial injury after AVO.

Ascending aortic wall degeneration in patients with bicuspid versus tricuspid aortic valve.

BACKGROUND: The magnitude of ascending aortic degeneration in patients with bicuspid aortic valves (BAV) is controversial. METHODS: The aim of this study was to investigate ascending aortic wall degeneration in patients with BAV as compared with tricuspid aortic valves (TAV). The ascending aortic wall of 67 consecutive patients was processed for histology and immunohistochemistry. The extent of surgery and wall degeneration were investigated. Unadjusted survival was evaluated by Kaplan-Meier analysis. Median follow-up for patients with BAV and TAV was 3.8 years (interquartile range [IQR] 3.5-4.1) and 3.7 years (IQR 3.4-3.9), respectively. RESULTS: There were 33 patients with BAV and 34 with TAV. Mid-ascending aorta diameter was 54 mm (IQR 50-60). Replacement of the aortic valve, together with an ascending aortic prosthesis, was more frequent in BAV vs TAV patients (24% vs. 3%, P = 0.013). However, medial fibrosis, elastic fiber thinning, incremental medial degeneration and smooth muscle cell nuclei loss were less prominent in BAV vs TAV patients (0.1 ± 0.4 vs. 0.8 ± 1.4, P = 0.016; 0.6 ± 1.4 vs. 1.6 ± 2.0, P = 0.027; 1.7 ± 0.7 vs. 2.2 ± 0.8, P = 0.045 and 2.3 ± 1.5 vs. 3.2 ± 1.3, P = 0.026, respectively). CONCLUSIONS: Since degeneration of the ascending aortic wall was seldom prominent, histopathology alone may not support the need for surgery of the dilated ascending aorta in BAV patients as compared with TAV patients.

Autonomic nerves in myocardial sleeves around caval veins: Potential role in cardiovascular mortality?

BACKGROUND: Quantitative changes in the cardiac autonomic nervous system may play an important role in the pathogenesis of various cardiovascular diseases. In the present morphological analysis, we aimed to study autonomic nerve density in myocardial sleeves and surrounding fibro-fatty tissue around caval veins. We correlated the nerve distribution with cardiovascular mortality and a history of atrial fibrillation. MATERIALS AND METHODS: A total of 24 autopsied adult hearts were excised together with the superior and inferior vena cava and grouped according to the immediate and underlying causes of death (cardiovascular vs. non-cardiovascular), and documented heart rhythm history (atrial fibrillation vs. sinus rhythm). The density of autonomic nerves was quantified by measuring the area of immunohistochemical staining for sympathetic (tyrosine hydroxylase, TH) and parasympathetic (choline acetyltransferase, CHAT) nerves and ganglia. Growth-associated protein 43 (GAP43) was used as a neural growth marker. RESULTS: The mean density of TH-positive nerves in the superior vena cava myocardial sleeves was significantly decreased between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean density ± standard deviation (SD): 704.81±1016.41 µm2/mm2 vs. 2391.01±1841.37 µm2/mm2; P = .008). Similarly, the nerve density of GAP43-positive nerves in the superior vena cava myocardial sleeves was significantly lower in subjects with documented underlying cardiovascular cause of death (mean density ± SD: 884.74±1240.16 µm2/mm2 vs. 2132.89±1845.89 µm2/mm2; P = .040). The mean age was significantly higher in subjects with documented underlying cardiovascular vs. non-cardiovascular cause of death (mean age ± SD: 69.2±11.9 years, vs. 57.5±11.2 years, P = .016). No differences were found in nerve densities of TH-positive (953.01±1042.93 µm2/mm2 vs. 919.26±1677.58 µm2/mm2), CHAT-positive (180.8±532.9 µm2/mm2 vs. 374.22±894.76 µm2/mm2), and GAP43-positive nerves (593.58±507.97 µm2/mm2 vs. 1337.34±1747.69 µm2/mm2) in myocardial sleeves around the inferior vena cava between groups with documented immediate cardiovascular vs. non-cardiovascular cause of death. Similarly, no differences were found between groups with documented underlying cardiovascular vs. non-cardiovascular cause of death (TH: 717.23±887.31 µm2/mm2 vs. 1365.51±2149.10 µm2/mm2; CHAT: 256.18±666.86 µm2/mm2 vs. 368.53±959.47 µm2/mm2; GAP43: 661.21±839.51 µm2/mm2 vs. 1759.90±2008.80 µm2/mm2). Moreover, there was no association found in nerve densities between subjects with documented atrial fibrillation vs. sinus rhythm (TH: 235.07±425.69 µm2/mm2 vs. 1166.08±1563.84 µm2/mm2; CHAT: 648.59±1017.33 µm2/mm2 vs. 175.31±641.65 µm2/mm2; GAP43: 990.17±1315.18 µm2/mm2 vs. 1039.86±1467.23 µm2/mm2). CONCLUSIONS: Decrease of superior vena cava myocardial sleeve sympathetic nerves may be associated with cardiovascular mortality and/or aging. No difference in autonomic innervation was found between subjects with documented atrial fibrillation vs. sinus rhythm.

Once after a full moon: acute type A aortic dissection and lunar phases.

OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD. METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period). RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated. CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.

History of cancer and survival after coronary artery bypass grafting: Experiences from the SWEDEHEART registry.

OBJECTIVE: To explore the currently unknown association between history of cancer at the time of coronary artery bypass grafting (CABG) and long-term survival. METHODS: All patients (n = 82,137) undergoing isolated first-time CABG in Sweden during 1997-2015 were included in this retrospective population-based cohort study. Individual patient data from the SWEDEHEART registry and 4 other mandatory nationwide health care registries were merged. Multivariable Cox proportional hazards regression and competing risk models adjusted for age and gender were used to assess associations between history of cancer, and long-term all-cause, cardiovascular and cancer mortality. Median follow-up was 9.0 years (interquartile range, 4.8-13.1). RESULTS: Altogether, 6819 (8.3%) of the patients had a history of cancer. The annual prevalence increased from 3.8% in 1997 to 14.8% in 2015. Patients with a history of cancer were older (72 vs 66 years; P < .001) and had more comorbidities. Long-term all-cause mortality was significantly greater in patients with a history of cancer (45.7% vs 22.9% at 10 years; adjusted hazard ratio, 1.33; 95% confidence interval [CI], 1.28-1.38, P < .001). According to the competing risk models, history of cancer was associated with an increased risk for cancer death (subdistribution hazard ratio, 2.45; 95% CI, 2.28-2.63, P < .001) but not cardiovascular death (subdistribution hazard ratio, 0.88; 95% CI, 0.83-0.94, P < .001). CONCLUSIONS: The proportion of patients undergoing CABG with a history of cancer has increased over time. History of cancer at the time of surgery is associated with increased cancer deaths over time but not cardiovascular deaths. The same cardiovascular prognosis after CABG can be expected regardless of cancer history.