Computational estimates of annular diameter reveal genetic determinants of mitral valve function and disease.

The fibrous annulus of the mitral valve plays an important role in valvular function and cardiac physiology, while normal variation in the size of cardiovascular anatomy may share a genetic link with common and rare disease. We derived automated estimates of mitral valve annular diameter in the 4-chamber view from 32,220 MRI images from the UK Biobank at ventricular systole and diastole as the basis for GWAS. Mitral annular dimensions corresponded to previously described anatomical norms, and GWAS inclusive of 4 population strata identified 10 loci, including possibly novel loci (GOSR2, ERBB4, MCTP2, MCPH1) and genes related to cardiac contractility (BAG3, TTN, RBFOX1). ATAC-Seq of primary mitral valve tissue localized multiple variants to regions of open chromatin in biologically relevant cell types and rs17608766 to an algorithmically predicted enhancer element in GOSR2. We observed strong genetic correlation with measures of contractility and mitral valve disease and clinical correlations with heart failure, cerebrovascular disease, and ventricular arrhythmias. Polygenic scoring of mitral valve annular diameter in systole was predictive of risk mitral valve prolapse across 4 cohorts. In summary, genetic and clinical studies of mitral valve annular diameter revealed genetic determinants of mitral valve biology, while highlighting clinical associations. Polygenic determinants of mitral valve annular diameter may represent an independent risk factor for mitral prolapse. Overall, computationally estimated phenotypes derived at scale from medical imaging represent an important substrate for genetic discovery and clinical risk prediction.

Sex Differences and Similarities in Valvular Heart Disease.

As populations age worldwide, the burden of valvular heart disease has grown exponentially, and so has the proportion of affected women. Although rheumatic valve disease is declining in high-income countries, degenerative age-related causes are rising. Calcific aortic stenosis and degenerative mitral regurgitation affect a significant proportion of elderly women, particularly those with comorbidities. Women with valvular heart disease have been underrepresented in many of the landmark studies which form the basis for guideline recommendations. As a consequence, surgical referrals in women have often been delayed, with worse postoperative outcomes compared with men. As described in this review, a more recent effort to include women in research studies and clinical trials has increased our knowledge about sex-based differences in epidemiology, pathophysiology, diagnostic criteria, treatment options, outcomes, and prognosis.

The systemic-immune-inflammation index predicts the recurrence of atrial fibrillation after cryomaze concomitant with mitral valve surgery.

BACKGROUND AND AIMS: Inflammation plays a key role in the initiation and progression of atrial fibrillation (AF). The systemic inflammation indexes are easily evaluated and predict AF development. However, it's role in prediction of recurrence of AF is unknown. We aim to explore the association between the systemic inflammation indexes and recurrence of AF in patients underwent cryoablation (CryoMaze) concomitant with mitral valve surgery. METHODS: We examined systemic inflammation indexes during perioperative period in 122 patients between 2015 and 2018. Systemic inflammation indexes were developed by systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocytes to monocytes ratio. Univariate and multivariate analyses were performed to examine the association of each markers with recurrence of AF. RESULTS: Of the 122 patients included in this study, 22 patients (18%) experienced AF recurrence after CryoMaze concomitant with mitral valve surgery. There is no significant difference between each systemic inflammation indexes before surgery and recurrence of AF. In univariate analysis, MLR after surgery 3 days, PLR, MPLR, NLR, SII after surgery 7 days were able to predict recurrence of AF. In multivariate analyses, SII ≥ 1696 independently predicted recurrence (OR, 3.719; 95% CI, 1.417-9.760). Interestingly, baseline SII showed no significant in prediction of recurrence. It was sharply elevated after surgery and dropped slowly. In patients of recurrence, SII after 7 days of surgery increased again. CONCLUSIONS: The raised SII again was associated with an increased risk of the postoperative recurrence of AF and independently predicted the late recurrence of AF after CryoMaze concomitant with mitral valve surgery.

Hsa_circ_0000437 upregulates and promotes disease progression in rheumatic valvular heart disease.

BACKGROUND: Currently, the diagnosis and outcome of rheumatic valvular heart disease (RVHD) are less than ideal, and there are no accurate biomarkers. Circular RNA (circRNA) might participate in the occurrence and development of RVHD. MATERIALS AND METHODS: We use circRNA microarray to filter out the target has_circ_0000437. qRT-PCR was used to measure the expression levels of hsa_circ_0000437 in RVHD plasma samples. We assessed the diagnostic value of hsa_circ_0000437 in RVHD. Cell function in vitro experiment was to explore the effect of has_circ_0000437 on RVHD. RESULTS: Has_circ_0000437 is highly expressed in RVHD (p < 0.001). has_circ_0000437 has the diagnostic value in RVHD. In RVHD, hsa_circ_0000437 can promote cell proliferation and migration but inhibits its apoptosis. This may be due to the combination of has_circ_0000437 and target miRNA in the cytoplasm that affects the progress of RVHD. CONCLUSIONS: Has_circ_0000437 can promote the process of RVHD and may be a potential for the diagnosis and treatment of RVHD.

Aortic valve replacement via right anterolateral minithoracotomy: preventing adverse events during the initial learning curve.

BACKGROUND: Despite excellent outcomes and reduced invasiveness, the right anterolateral thoracotomy approach for aortic valve replacement (RALT-AVR) has not been broadly adopted. This study provides results regarding the initial experience and learning curve of a single surgeon performing this procedure. METHODS: Periprocedural details and postoperative outcomes of the first 100 consecutive patients who underwent RALT-AVR at our institution were retrospectively analyzed. We conducted a cumulative sum analysis of surgical failure, defined as occurrence of 30-day-mortality, surgical revision for bleeding, conversion to sternotomy, 3rd degree heart block, paravalvular leakage, postoperative stroke or mean transvalvular gradient >20 mmHg. RESULTS: The cohort was of low surgical risk (mean EuroSCORE II 1.31%±0.85, mean STS PROM 1.45%±0.97), 58% were males. Median cross-clamp time was 67.5 (57.8-76) min, median CPB time 105 (91.8-119) min, and median operation time 164.5 (144.5-183.2) min. There were no conversions to full sternotomy, 4 cases of revision for bleeding and 2 pacemaker implantations for 3rd degree heart block. Prosthesis function was good (median ΔPmean 10.9 [7.4-13.6] mmHg). Thirty-day-mortality was 0%. The log-likelihood graph never crossed the upper boundary, and after a steady decrease, crossed the lower boundary at 93 patients. CONCLUSIONS: RALT-AVR can be performed with acceptable procedural times and satisfactory outcomes. For a well-trained surgeon, adapting to this new procedure does not expose patients to an increased risk, when patient selection and procedural planning are applied appropriately. Cumulative sum failure analysis is an appropriate tool to monitor the transition from standard AVR to the technically more demanding RALT-AVR.

Cardiac structural and functional abnormalities in primary hyperparathyroidism.

PURPOSE: Studies on cardiac structural and functional abnormalities in primary hyperparathyroidism (PHPT) have yielded conflicting and inconsistent results. In this prospective case-control study, we sought to compare cardiac structure and function in symptomatic PHPT patients and controls. METHODS: One hundred consecutive symptomatic PHPT patients and 113 matched controls underwent echocardiographic evaluation by the same operator. RESULTS: Left ventricular mass index (LVMI) was significantly higher in patients as compared to controls, (median of 90.95 g/m2 vs 86.5 g/m2, p = 0.041). Patients had significantly lower early trans-mitral diastolic flow (E velocity) as compared to controls (57.13 ± 14.88 vs 64.76 ± 15.45 cm/s, p < 0.001). Patients also had significantly lower early to late mitral annular velocity (E/A) as compared to controls (0.98 ± 0.37 vs 1.10 ± 0.34, p 0.013). Patients had higher frequency of aortic valve calcification (29% vs 2.65%, p < 0.001), mitral annular calcification (23% vs. 4.42%, p < 0.001), myocardial and septal calcifications (25% vs none, p < 0.001) as compared to controls. Serum PTH, calcium and uric acid significantly correlated with calcifications. Serum calcium showed a negative correlation with E/A ratio. CONCLUSIONS: Symptomatic patients with PHPT have substantial cardiac structural and functional abnormalities. These abnormalities include elevated LVMI, diastolic dysfunction, and aortic valve, mitral annular, septal and myocardial calcifications. We strongly suggest and conclude that the evaluation of PHPT patients should not only include traditional end organs like bones and kidneys but also the cardiovascular system in the form of echocardiography to detect subclinical cardiac dysfunction so that the cardiovascular health of such patients can be optimized.

Del Nido versus HTK cardioplegia for myocardial protection during adult complex valve surgery: a retrospective study.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. METHODS: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. RESULTS: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. CONCLUSIONS: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.

On the shape and structure of the murine pulmonary heart valve.

Murine animal models are an established standard in translational research and provides a potential platform for studying heart valve disease. To date, studies on heart valve disease using murine models have been hindered by a lack of appropriate methodologies due to their small scale. In the present study, we developed a multi-scale, imaging-based approach to extract the functional structure and geometry for the murine heart valve. We chose the pulmonary valve (PV) to study, due to its importance in congenital heart valve disease. Excised pulmonary outflow tracts from eleven 1-year old C57BL/6J mice were fixed at 10, 20, and 30 mmHg to simulate physiological loading. Micro-computed tomography was used to reconstruct the 3D organ-level PV geometry, which was then spatially correlated with serial en-face scanning electron microscopy imaging to quantify local collagen fiber distributions. From the acquired volume renderings, we obtained the geometric descriptors of the murine PV under increasing transvalvular pressures, which demonstrated remarkable consistency. Results to date suggest that the preferred collagen orientation was predominantly in the circumferential direction, as in larger mammalian valves. The present study represents a first step in establishing organ-level murine models for the study of heart valve disease.

Safety of Phosphodiesterase-5 Inhibitors in Valvular Heart Disease.

ABSTRACT: Erectile dysfunction is a common entity in clinical practice. Primary erectile dysfunction, not related to vasculopathy or psychiatric disorder, can be readily treated with phosphodiesterase inhibitors. These drugs have many physiologic effects that can alter a patient's hemodynamic profile considerably, especially in the presence of concomitant structural heart disease, specifically valvular heart disease. Although some contraindications to the use of PDE5 inhibitors in patients with cardiovascular disease are defined, the effect of these drugs in the presence of valvular heart disease is not well documented. The purpose of this review is to analyze the data regarding the safety of PDE5 inhibitors in patients with valvular heart disease.

Long-term results after mitral valve surgery using minimally invasive versus sternotomy approach: a propensity matched comparison of a large single-center series.

BACKGROUND: Mitral valve (MV) surgery has traditionally been performed by conventional sternotomy (CS), but more recently minimally invasive surgery (MIS) has become another treatment option. The aim of this study is to compare short- and long-term results of MV surgery after CS and MIS. METHODS: This study was a retrospective propensity-matched analysis of MV operations between January 2005 and December 2015. RESULTS: Among 1357 patients, 496 underwent CS and 861 MIS. Matching resulted in 422 patients per group. The procedure time was longer with MIS than CS (192 vs. 185 min; p = 0.002) as was cardiopulmonary bypass time (133 vs. 101 min; p < 0.001) and X-clamp time (80 vs. 71 min; p < 0.001). 'Short-term' successful valve repair was higher with MIS (96.0% vs. 76.0%, p < 0.001). Length of hospital stay was shorter in MIS than CS patients (10 vs. 11 days; p = 0.001). There was no difference in the overall 30-day mortality rate. Cardiovascular death was lower after MIS (1.2%) compared with CS (3.8%; OR 0.30; 95%CI 0.11-0.84). The difference did not remain significant after adjustment for procedural differences (aOR 0.40; 95%CI 0.13-1.25). Pacemaker was required less often after MIS (3.3%) than CS (11.2%; aOR 0.31; 95%CI 0.16-0.61), and acute renal failure was less common (2.1% vs. 11.9%; aOR 0.22; 95%CI 0.10-0.48). There were no significant differences with respect to rates of stroke, myocardial infarction or repeat MV surgery. The 7-year survival rate was significantly better after MIS (88.5%) than CS (74.8%; aHR 0.44, 95%CI 0.31-0.64). CONCLUSION: This study demonstrates that good results for MV surgery can be obtained with MIS, achieving a high MV repair rate, low peri-procedural morbidity and mortality, and improved long-term survival.

Valvular Disease and Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome of shortness of breath and/or exercise intolerance secondary to elevated left ventricular filling pressures at rest or with exertion either as a result of primary diastolic dysfunction (primary HFpEF) or secondary to specific underlying causes (secondary HFpEF). In secondary HFpEF, early intervention of underlying valvular heart disease generally improves symptoms and prolongs survival. In primary HFpEF, there is increasing awareness of the existence and prognostic implications of secondary atrioventricular valve regurgitation. Further studies will clarify their mechanisms and the effectiveness of valvular intervention in this intriguing HFpEF subgroup.

Optimizing Timing of Valve Intervention in Patients With Asymptomatic Severe Valvular Heart Disease.

The management of valvular heart disease has changed dramatically over the past decade with advances in cardiac imaging, the use of novel biomarkers, and the development of transcatheter valve repair and replacement technology. International society guidelines have kept pace to provide recommendations for diagnosis, follow-up, and timing of intervention. The most challenging patient cohort for clinicians are patients with asymptomatic severe disease in whom the optimal timing of intervention can be ill-defined. It is a fine balance between the risks of early intervention on asymptomatic patients and improving patient outcomes by preventing long-term cardiac complications. The key in optimal patient management is gathering the necessary information on patient risk and combining that with the risk, efficacy, and durability of valve interventions to arrive at the appropriate timing for intervention. This group of patients will be the focus of this review as we delve into the natural history, recommended follow-up, and indications for intervention in patients with degenerative aortic and mitral valve disease.

Genetics of canine myxomatous mitral valve disease.

Myxomatous mitral valve disease (MMVD) is the most common heart disease and cause of cardiac death in domestic dogs. MMVD is characterised by slow progressive myxomatous degeneration from the tips of the mitral valves onwards with subsequent mitral valve regurgitation, and left atrial and ventricular dilatation. Although the disease usually has a long asymptomatic period, in dogs with severe disease, mortality is typically secondary to left-sided congestive heart failure. Although it is not uncommon for dogs to survive long enough in the asymptomatic period to die from unrelated causes; a proportion of dogs rapidly advance into congestive heart failure. Heightened prevalence in certain breeds, such as the Cavalier King Charles Spaniel, has indicated that MMVD is under a genetic influence. The genetic characterisation of the factors that underlie the difference in progression of disease is of strong interest to those concerned with dog longevity and welfare. Advanced genomic technologies have the potential to provide information that may impact treatment, prevalence, or severity of MMVD through the elucidation of pathogenic mechanisms and the detection of predisposing genetic loci of major effect. Here we describe briefly the clinical nature of the disorder and consider the physiological mechanisms that might impact its occurrence in the domestic dog. Using results from comparative genomics we suggest possible genetic approaches for identifying genetic risk factors within breeds. The Cavalier King Charles Spaniel breed represents a robust resource for uncovering the genetic basis of MMVD.

Evaluation of Staged TCAR and Cardiac Surgery or Structural Heart Intervention.

INTRODUCTION: The optimal treatment strategy for patients with concomitant carotid and cardiac disease remains controversial. Transcarotid artery revascularization stenting with reversed flow protection (TCAR) has achieved results equivalent to carotid endarterectomy (CEA) in high risk patients. METHODS: A retrospective review of all patients at a single center who received staged TCAR prior to cardiac intervention was performed. RESULTS: 37 patients underwent 42 TCAR procedures prior to cardiac intervention (25 requiring open cardiac surgery and 12 requiring percutaneous intervention). There were no myocardial or neurological complications following TCAR prior to cardiac intervention. Three patients (8%) developed a neck hematoma which required evacuation. CONCLUSION: A staged approach to combined carotid and cardiac pathology with TCAR prior to cardiac intervention appears to be a safe and effective strategy.

Suture reduction of the borderline ascending aortic dilatation during aortic valve replacement.

BACKGROUND: This study was conducted to evaluate the efficacy of simple suture reduction of the ascending aorta (SRA) performed with aortic valve replacement (AVR) in patients with borderline ascending aortic dilatation (45-50 mm). METHODS: Ninety-eight patients (ascending aortic diameter 47.7±3.4 mm) who underwent concomitant SRA with AVR were enrolled. Median follow-up duration was 83 (IQR 27-173) months. Computed tomographic angiography (CTA) follow-up was performed at 71 (47-149) months after surgery (N.=69). At least two CTA scans were performed in 34 patients (interval = 63 [46, 156] months). Early and long-term outcomes were evaluated, and dilatation rate (mm/year) of the repaired aorta was analyzed. Major adverse aortic events (MAEs) were defined as death related to aortic events, including sudden death, aortic rupture or dissection, aortic reoperation and recurrent aortic aneurysm (>45 mm). RESULTS: Early mortality rate was 2.0%. No patients had postoperative complications associated with SRA. A recurrent aortic aneurysm (>45 mm) was found in nine patients, but none of the patients had an ascending aorta diameter >50 mm. A multivariable analysis demonstrated that neither preoperative diameter of the ascending aorta nor bicuspid valve was associated with dilatation of the repaired aorta. Co-existing coronary artery disease was associated with both recurrent aneurysm and increased dilatation rate after SRA. There were two cases of sudden death and no one suffered from aortic dissection, rupture or aortic reoperation. Ten- and 20-year freedom rates from MAE were 90.3% and 79.3%, respectively. CONCLUSIONS: Concomitant SRA might be a safe and effective surgical alternative to ascending aorta replacement in AVR patients with borderline ascending aortic dilatation regardless of aortic valve pathology.