Comprehensive clinical application analysis of artificial intelligence-enabled electrocardiograms for screening multiple valvular heart diseases.

BACKGROUND: Valvular heart disease (VHD) is becoming increasingly important to manage the risk of future complications. Electrocardiographic (ECG) changes may be related to multiple VHDs, and (AI)-enabled ECG has been able to detect some VHDs. We aimed to develop five deep learning models (DLMs) to identify aortic stenosis, aortic regurgitation, pulmonary regurgitation, tricuspid regurgitation, and mitral regurgitation. METHODS: Between 2010 and 2021, 77,047 patients with echocardiography and 12-lead ECG performed within 7 days were identified from an academic medical center to provide DLM development (122,728 ECGs), and internal validation (7,637 ECGs). Additional 11,800 patients from a community hospital were identified to external validation. The ECGs were classified as with or without moderate-to-severe VHDs according to transthoracic echocardiography (TTE) records, and we also collected the other echocardiographic data and follow-up TTE records to identify new-onset valvular heart diseases. RESULTS: AI-ECG adjusted for age and sex achieved areas under the curves (AUCs) of >0.84, >0.80, >0.77, >0.83, and >0.81 for detecting aortic stenosis, aortic regurgitation, pulmonary regurgitation, tricuspid regurgitation, and mitral regurgitation, respectively. Since predictions of each DLM shared similar components of ECG rhythms, the positive findings of each DLM were highly correlated with other valvular heart diseases. Of note, a total of 37.5-51.7% of false-positive predictions had at least one significant echocardiographic finding, which may lead to a significantly higher risk of future moderate-to-severe VHDs in patients with initially minimal-to-mild VHDs. CONCLUSION: AI-ECG may be used as a large-scale screening tool for detecting VHDs and a basis to undergo an echocardiography.

New therapeutic perspectives for vascular and valvular calcifications in chronic kidney disease.

PURPOSE OF REVIEW: Vascular and valvular calcification are associated with cardiovascular morbidity and mortality in people with chronic kidney disease (CKD). Uncertainty exists regarding therapeutic strategies to attenuate calcification. This review outlines the pathophysiological mechanisms contributing to vascular and valvular calcification, considers the mechanisms of action of therapeutic interventions, and reports the latest outcomes from interventional studies. RECENT FINDINGS: Conventional therapies targeted at CKD-mineral and bone disorder (MBD) modulation have yielded conflicting or inconclusive results. Magnesium and vitamin K supplementation appear to offer attenuation of coronary artery calcification but inconsistent findings justify the need for further studies. Strategies targeting hydroxyapatite formation such as sodium thiosulphate and hexasodium fytate show promise and are worthy of further evaluation. The serum calcification propensity assay (T50) correlates with severity and progression; it holds promise as a potential future clinical tool for screening monitoring calcification risk. SUMMARY: Whilst knowledge of the pathophysiology of vascular calcification has grown and therapeutic approaches appear promising, as yet no medication has been approved to treat vascular or valvular calcification, or calciphylaxis.

Relation of body mass index to long-term survival and cardiac remodelling for patients undergoing mitral valve replacement surgery.

BACKGROUND AND AIMS: Studies have demonstrated that obesity is paradoxically associated with reduced mortality following cardiac surgery. However, these studies have treated various types of cardiac surgery as a single entity. With mitral valve (MV) surgeries being the fastest-growing cardiac surgical interventions in North America, the purpose of this study was to identify the impact of body mass index (BMI) on long-term survival and cardiac remodelling of patients undergoing MV replacement (MVR). METHODS AND RESULTS: In this retrospective, single-center study, 1071 adult patients who underwent an MVR between 2004 and 2018 were stratified into five BMI groups (<20, 20-24.9, 25-29.9, 30-34.9, >35). Cox proportional hazard regression models were used to determine the association between BMI and all-cause mortality. Patients who were underweight had significantly higher all-cause mortality rates at the longest follow-up (median 8.2 years) than patients with normal weight (p = 0.01). Patients who were in the obese group had significantly higher readmission rates due to myocardial infarction (MI) at the longest follow-up (p = 0.017). Subgroup analysis revealed a significant increase in long-term all-cause mortality for female patients who were underweight. Significant changes in left atrial size, mitral valve peak and mean gradients were seen in all BMI groups. CONCLUSIONS: For patients undergoing mitral valve replacement, BMI is unrelated to operative outcomes except for patients who are underweight.

Cardiac evaluation in pregnant patients with dyspnea and palpitations.

BACKGROUND: Symptoms of underlying cardiac disease in pregnancy can often be mistaken for common complaints because of normal physiological changes in pregnancy. Echocardiographic evaluation of patients with symptoms of palpitations and dyspnea can detect structural changes and identify high-risk features. OBJECTIVE: This study aimed to examine transthoracic echocardiograms of perinatal individuals completed for palpitations or dyspnea to determine the frequency of identifying structural changes. STUDY DESIGN: This was a retrospective cohort study of all perinatal individuals with a transthoracic echocardiogram at a single academic center between October 1, 2017, and May 1, 2022. The indication for the echocardiogram, demographics, and clinical characteristics were recorded. Transthoracic echocardiograms with any abnormal findings noted in the transthoracic echocardiogram report were reviewed and categorized into findings of congenital heart disease, valvular disease, pericardial effusion, evidence of ischemia or wall motion abnormalities, abnormal diastolic or systolic function, and other. RESULTS: Of 539 transthoracic echocardiograms completed on 478 individuals who were pregnant or in the 12-week postpartum period, 96 (17.8%) had an indication of palpitations, and 32 (5.9%) had an indication of dyspnea. Abnormal findings were seen in 21.9% of patients with palpitations and in 34.4% of patients with dyspnea. In patients with palpitations who had abnormal findings, 33.3% had congenital heart disease; 33.3% had mild valvular disease, including mitral valve prolapse; 19.0% had a pericardial effusion; and 14.3% had evidence of ischemia or wall motion defects. Abnormal transthoracic echocardiogram findings in the dyspnea cohort included ischemia or wall motion defects (27.3%), mild valvular disease or mitral valve prolapse (36.4%), and abnormal systolic or diastolic function (36.4%). CONCLUSION: Many of the transthoracic echocardiograms completed for patients with dyspnea or palpitations identified no structural abnormality; however, in 1 of 3 to 1 of 4 patients, underlying structural heart disease was identified. Although some of these abnormalities were unlikely to change delivery plans, such as mild valvular disease or small effusions, other abnormalities, such as ischemia, congenital abnormalities, and abnormal systolic or diastolic function, were likely to have implications for pregnancy and postpartum management.

Evaluating left atrial strain and left ventricular diastolic strain rate as markers for diastolic dysfunction in patients with mitral annular calcification.

BACKGROUND: Mitral annular calcification (MAC) poses many challenges to the evaluation of diastolic function using standard echocardiography. Left atrial (LA) strain and left ventricular early diastolic strain rate (DSr) measured by speckle-tracking echocardiography (STE) are emerging techniques in the noninvasive evaluation of diastolic function. We aim to evaluate the utility of LA strain and early DSr in predicting elevated left ventricular filling pressures (LVFP) in patients with MAC and compare their effectiveness to ratio of mitral inflow velocity in early and late diastole (E/A). METHODS: We included adult patients with MAC who presented between January 1 and December 31, 2014 and received a transthoracic echocardiogram (TTE) and cardiac catheterization with measurement of LVFP within a 24-h period. We used Spearman's rank correlation coefficient to assess associations of LA reservoir strain and average early DSr with LVFP. Receiver operating characteristic (ROC) curves were computed to assess the effectiveness of LA strain and DSr in discriminating elevated LVFP as a dichotomized variable and to compare their effectiveness with E/A ratio categorized according to grade of diastolic dysfunction. RESULTS: Fifty-five patients were included. LA reservoir strain demonstrated poor correlation with LVFP (Spearman's rho = 0.03, p = 0.81) and poor discriminatory ability for detecting elevated LVFP (AUC = 0.54, 95% CI 0.38-0.69). Categorical E/A ratio alone also demonstrated poor discriminatory ability (AUC = 0.53, 95% CI 0.39-0.67), and addition of LA reservoir strain did not significantly improve effectiveness (AUC = 0.58, 95% CI 0.42-0.74, p = 0.56). Average early DSr also demonstrated poor correlation with LVFP (Spearman's rho = -0.19, p = 0.16) and poor discriminatory ability for detecting elevated LVFP (AUC = 0.59, 95% CI 0.44-0.75). Addition of average early DSr to categorical E/A ratio failed to improve effectiveness (AUC = 0.62, 95% CI 0.46-0.77 vs. AUC = 0.54, 95% CI 0.39-0.69, p = 0.38). CONCLUSIONS: In our sample, LA reservoir strain and DSr do not accurately predict diastolic filling pressure. Further research is required before LA strain and early DSr can be routinely used in clinical practice to assess filling pressure in patients with MAC.

Readmission-related outcomes of surgical versus transcatheter aortic valve replacement in patients aged 65 or older with bicuspid aortic valve.

BACKGROUND: There continues to be debate regarding the superiority of transcatheter (TAVR) over surgical aortic valve replacement (SAVR) in patients with bicuspid aortic valves (BAV). We aimed to compare outcomes during readmissions in elderly patients with BAV who underwent SAVR or TAVR. METHODS: Patients 65 years or older with BAV who underwent TAVR or isolated SAVR were identified using the National Readmission Database from 2012 through 2018. We compared outcomes during readmissions within 90 days after discharge from the index surgery. Propensity score matching was performed to adjust the baseline differences. RESULTS: During the study period, 8555 and 1081 elderly patients with BAV underwent SAVR and TAVR, respectively. The number of patients who underwent TAVR went up by 179 % from 2012 to 2018. Propensity score matching yielded 573 patients in each group. A total of 111 (19.4 %) in the SAVR group and 125 (21.8 %) in the TAVR group were readmitted within 90 days after the index surgery (p = .31). The mortality during the readmissions within 90 days was equivalent between the two groups (0.9 % in the SAVR group vs. 3.2 % in the TAVR group, p = .22). However, the median hospital cost was approximately doubled in the TAVR group during the readmission (18,250 dollars vs. 9310 dollars in the SAVR group, p < .001). CONCLUSIONS: Readmission within 90 days was common in both groups. While the mortality during the readmissions after the surgery was equivalent between the two groups, hospital cost was significantly more expensive in the TAVR group.

Percutaneous left atrial appendage occlusion in mitral valve disease: A Nationwide Readmission Database analysis.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) has emerged as a non-pharmacologic alternative to oral anticoagulation in reducing stroke risk in AF patients. However, patients with mitral valve disease (MVD), who are expected to have a significantly greater risk of left atrium (LA) thrombus formation and embolic stroke were excluded from randomized trials examining percutaneous LAAO. To address this gap, we present a national registry analysis of the use of LAAO among patients with MVD. METHODS: Using the National Readmissions Database, we performed a retrospective review of all hospitalizations for LAAO identified between September 2015 and November 2019. Of these, patients with ICD-10 codes for MVD were identified. Propensity matched (PSM) analysis was used to compare patients with MVD with a matched sample of patients undergoing LAAO with non-valvular AF. Outcomes examined included all-cause mortality, stroke, major bleeding, pericardial effusion (PE), and tamponade. RESULTS: 51,540 patients who underwent LAAO without a history of MVD and 3777 with a history of MVD were identified. Crude analysis demonstrated the odds of mortality, PE, and cardiac tamponade during index hospitalization to be higher in the MVD group. The length of stay and cost of index hospitalization were also slightly greater for the MVD group. A sample of 7649 patients (MVD: 3777 MVD and no MVD: 3872) were selected for PSM analysis with similar comorbidities across the two groups. In the PSM comparison, MVD was associated with higher risk of PE. The MVD group had a slightly higher rate of readmissions the association with PE remained at 30-day readmission (OR: 2.099 [1.360-3.238], p-value: <0.001). CONCLUSION: To our knowledge, this is the first study examining the use of LAAO among MVD patients. Our findings suggest that patients with MVD who underwent LAAO had a higher risk of post-procedural PE without an increase in mortality, stroke, or major bleeding. These results provide a rationale for considering LAAO as part of the stroke prevention strategy among patients with valvular AF.

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.

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.

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.

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.

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.

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.