Impact of commissural calcification on clinical outcome of percutaneous balloon mitral valvuloplasty; a retrospective cohort study of 876 patients.

BACKGROUND: Percutaneous balloon mitral valvuloplasty (PBMV) is the ACC/AHA class I recommendation for treating symptomatic rheumatic mitral stenosis with suitable valve morphology, less than moderate MR and absence of left atrium clot. The mitral valve restenosis and significant mitral regurgitation (MR) are known adverse outcomes of PBMV. This study aimed to evaluate the outcomes of PBMV in patients with severe mitral stenosis and the effect of Commissural Calcification (CC) on the outcomes. METHODS: In this single-center retrospective cohort study, 876 patients who underwent PBMV were categorized into three groups based on their Wilkins score (Group I: score ≤ 8, Group II: score 9-10, and Group III: score 11-12). Patients were evaluated before, early after PBMV and at 6- and 24-month follow-ups. Main clinical outcomes were defined as significant restenosis and or symptomatic significant MR (moderate to severe and severe MR) or candidate for mitral valve replacement (MVR). The outcomes were compared between patients with and without CC. RESULTS: A total of 876 patients with mean age 46.4 ± 12.3 years (81.0% females) were categorized based on Wilkins score. 333 (38.0%) were in Group I, 501 (57.2%) were in Group II, and 42 (4.8%) were in Group III. CC was present in 175 (20.0%) of the patients, among whom 95 (54.3%) had calcification of the anterolateral commissure, 64 (36.6%) had calcification of the posteromedial commissure, and in 16 (9.1%) patients both commissures were calcified. There was a significant difference in Wilkins score between patients with and without CC (P < 0.001). CC was associated with higher odds of significant symptomatic MR at early and mid-term follow up (OR: 1.69, 95%CI 1.19-2.41, P = 0.003; and OR: 3.90, 95%CI 2.61-5.83, P < 0.001, respectively), but not with restenosis (P = 0.128). Wilkins Groups II and III did not show higher odds of significant symptomatic MR compared to Group I at early (II: P = 0.784; III: P = 0.098) and mid-term follow up (II: P = 0.216; III: P = 0.227). Patients in Wilkins Group II had higher odds of restenosis compared to Group I (OR: 2.96,95%CI: 1.35-6.27, P = 0.007). CONCLUSION: Commissural calcification (CC) is an independent predictor of the significant symptomatic MR (an important determinant of adverse outcome) following PBMV in the early and mid-term follow-up. Mitral valve restenosis occurs more in patients with higher Wilkins score compared to group I with score ≤ 8. Combined Wilkins score and CC should be considered for patient suitability for PBMV.

Implications of trial eligibility in patients with heart failure with mildly reduced or preserved ejection fraction.

AIMS: Clinical trials in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) commonly have detailed eligibility criteria. This may contribute to challenges with efficient enrolment and questions regarding the generalizability of trial findings. METHODS AND RESULTS: Patients with HFmrEF/HFpEF from a large US healthcare system were identified through a computable phenotype applied in linked imaging and electronic health record databases. We evaluated shared eligibility criteria from five recent/ongoing HFmrEF/HFpEF trials (PARAGON-HF, EMPEROR-Preserved, DELIVER, FINE-ARTS, and SPIRRIT-HFpEF) and compared clinical and echocardiographic features as well as outcomes between trial-eligible and trial-ineligible patients. Among 5552 patients with HFpEF/HFmrEF, 792 (14%) were eligible for trial consideration, having met all criteria assessed. Causes of ineligibility included lack of recent loop diuretics (37%), significant pulmonary disease (24%), reduced estimated glomerular filtration rate (17%), recent stroke/transient ischaemic attack (13%), or low natriuretic peptides (12%); 53% of ineligible patients had >1 reason for exclusion. Compared with eligible patients, ineligible patients were younger (age 71 vs. 75 years, P < 0.001) with higher rates of coronary artery disease (66% vs. 59%, P < 0.001) and peripheral vascular disease (40% vs. 33%, P < 0.001), but less mitral regurgitation, lower E/e' ratio, and smaller left atrial sizes. Both eligible and ineligible patients demonstrated high rates of structural heart disease consistent with HFpEF [elevated left atrial size or left ventricular (LV) hypertrophy/increased LV mass], although this was slightly higher among eligible patients (95% vs. 92%, P = 0.001). The two cohorts demonstrated similar LV global longitudinal strain along with a similar prevalence of atrial fibrillation/flutter, hypertension, and obesity. Ineligible patients had similar all-cause mortality (33% vs. 33% at 3 years) to those eligible but lower rates of heart failure hospitalization (20% vs. 28% at 3 years, P < 0.001). CONCLUSIONS: Among patients with HFmrEF/HFpEF from a large health system, approximately one in seven were eligible for major trials based on key criteria applied through a clinical computable phenotype. These findings highlight the large proportion of patients with HFmrEF/HFpEF ineligible for contemporary trials for whom the generalizability of trial findings may be questioned and further investigation would be beneficial.

Diagnosing Coronary Artery Disease in the Patient Presenting with Stable Ischemic Heart Disease: The Role of Anatomic versus Functional Testing.

There are unique advantages and disadvantages to functional versus anatomic testing in the work-up of patients who present with symptoms suggestive of obstructive coronary artery disease. Evaluation of these individuals starts with an assessment of pre-test probability, which guides subsequent testing decisions. The choice between anatomic and functional testing depends on this pre-test probability. In general, anatomic testing has particular utility among younger individuals and women; while functional testing can be helpful to rule-in ischemia and guide revascularization decisions. Ultimately, selection of the most appropriate test should be individualized to the patient and clinical scenario.

Echocardiographic Features Beyond Ejection Fraction and Associated Outcomes in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction.

BACKGROUND: Heart failure (HF) guidelines recommend assessment of left ventricular ejection fraction (LVEF) to classify patients and guide therapy implementation. However, LVEF alone may be insufficient to adequately characterize patients with HF, especially those with mildly reduced or preserved LVEF. Recommendations on additional testing are lacking, and there are limited data on use of echocardiographic features beyond LVEF in patients with heart failure with mildly reduced or preserved LVEF. METHODS: In patients with HF with mildly reduced or preserved LVEF identified in a large US health care system, the association of the following metrics with mortality was evaluated: LV global longitudinal strain (LV GLS>-16), left atrial volume index (>28 mL/m2), left ventricular hypertrophy (LVH), and E/e´>13 and e´<9. A multivariable model for mortality was constructed including age, sex, and key comorbidities followed by stepwise selection of echocardiographic features. Characteristics and outcomes of subgroups with normal versus abnormal LV GLS and LVEF were evaluated. RESULTS: Among 2337 patients with complete echocardiographic data assessed between 2017 and 2020, the following features were associated with all-cause mortality on univariate analysis over 3 years of follow-up: E/e´+e´, LV GLS, left atrial volume index (all P<0.01). In the multivariable model (C-index=0.65), only abnormal LV GLS was independently associated with all-cause mortality (HR, 1.35 [95% CI, 1.11-1.63]; P=0.002). Among patients with LVEF>55%, 498/1255 (40%) demonstrated abnormal LV GLS. Regardless of specific LVEF, patients with abnormal LV GLS demonstrated a higher burden of multiple comorbidities and higher event rates compared with patients with normal LV GLS. CONCLUSIONS: In a large, real-world HF with mildly reduced or preserved LVEF population, echocardiographic features, led by LV GLS, were associated with adverse outcomes irrespective of LVEF. A large proportion of patients demonstrate adverse myocardial function by LV GLS despite preserved LVEF and may represent a key cohort of interest for HF medical therapies and future clinical studies.

Imaging Considerations and Clinical Implications of Mitral Annular Disjunction.

Mitral annular disjunction is increasingly recognized as an important anatomic feature of mitral valve disease. The presence of mitral annular disjunction, defined as separation between the left atrial wall at the point of mitral valve insertion and the left ventricular free wall, has been associated with increased degeneration of the mitral valve and increased incidence of sudden cardiac death. The clinical importance of this entity necessitates standard reporting on cardiovascular imaging reports if patients are to receive adequate risk stratification and management. We provide a narrative review of the literature pertaining to mitral annular disjunction, its clinical implications, and areas needing further research.

Clinical trajectory of patients with a worsening heart failure event and reduced ventricular ejection fraction.

BACKGROUND: Recent data suggest that patients with heart failure with reduced ejection fraction (HFrEF) and worsening heart failure (WHF) have potential for greater benefit from newer HF therapies. We investigated characteristics and outcomes of patients with HFrEF and WHF by severity of left ventricular dysfunction. METHODS: We identified patients with chronic symptomatic HFrEF (left ventricular ejection fraction [LVEF] ≤35%) and evidence of WHF (emergency department visit or hospitalization for acute HF within 12 months of index echocardiogram) treated at Duke University between 1/2009 and 12/2018. Patients were stratified by LVEF≤25% or 26% to35%. Cox models were used to estimate cause-specific hazard ratios and 5-year event incidence of death and hospitalization across the range of LVEF. RESULTS: Of 2823 patients with HFrEF and WHF, 1620 (57.4%) had an LVEF≤25% and 1203 (42.6%) had an LVEF 26% to35%. Compared to patients with LVEF 26% to35%, those with LVEF≤25% were younger and more commonly men with a lower cardiovascular comorbidity burden. Patients with LVEF≤25% were less commonly on beta blockers (85.9% vs 90.5%) but more commonly treated with mineralocorticoid receptor antagonists (49.3% vs 41.1%) and implantable defibrillators (41.3% vs 28.2%). Patients with LVEF≤25% had significantly higher hazards for death (HR 1.24 [95% CI 1.11 - 1.38]), all-cause hospitalization (HR 1.21 [95% CI 1.10 - 1.33]), and HF hospitalization (HR 1.25 [95% CI 1.1 - 1.38]) through 5-years. CONCLUSIONS: More than half of patients with chronic HFrEF and WHF have severe LV dysfunction. Important differences in comorbidities, HF therapies, and outcomes exist between those with LVEF≤25% and those with LVEF 26% to35%.

Early Identification of Patients at Risk for Incident Heart Failure With Preserved Ejection Fraction: Novel Approach to Echocardiographic Trends.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) continues to increase in prevalence with a 50% mortality rate within 3 years of diagnosis, but lacking effective evidence-based therapies. Specific echocardiographic markers are not typically used to trigger alarm before acute HFpEF decompensation. The goal of this study was to retrospectively track changes in echocardiographic markers leading to the time of incident HFpEF hospitalization. METHODS AND RESULTS: In a single-center, retrospective analysis, patients with HFpEF admitted between 2007 and 2014 were identified using the International Classification of Diseases, 9th Revision with search refined using the European Society of Cardiology HFpEF guidelines. Using linear mixed effects models, changes in echocardiographic markers preceding acute HF decompensation owing to incident HFpEF were analyzed. We report on an incident HFpEF cohort of 242 patients, extending 18 years retrospectively, and including 675 echocardiograms analyzed from the overall sample at 14 distinct time intervals before acute decompensation. The regression models demonstrated 3 echocardiographic markers with statistically significant increases across multiple time intervals including, arterial elastance (P = .006), right atrial pressure estimate (P < .001), and right ventricular systolic pressure (P = .006). Other echocardiographic markers had individual time intervals with significant increases before acute decompensation, including (a) left atrial diameter, 8 to 10 years before HFpEF diagnosis, (b) left ventricular filling pressure 2 to 6 years before HFpEF diagnosis, (c) ventricular elastance 3 to 6 months before HFpEF diagnosis, and (d) ventricular elastance/arterial elastance as early as 10 to 20 years and as late as 3 to 6 months before HFpEF diagnosis. Furthermore, African Americans presented with incident HFpEF at an average younger age than White patients (65.6 ± 15.2 years vs. 76.7 years ± 11.7, P < .001). CONCLUSIONS: Noninvasive echocardiographic markers associated with incident HFpEF diagnosis showed long, mid, and acute range, significant changes as far back as 10 to 20 years and as close as 3 to 6 months before acute HFpEF decompensation. Including a diverse study cohort is critical to understanding the phenotypic differences of HFpEF. This hypothesis-generating study identified a novel approach to identifying trends in echocardiographic markers that may be used as a signal of impending incident HFpEF.

Acute cardiovascular hospitalizations and illness severity before and during the COVID-19 pandemic.

BACKGROUND: Cardiovascular disease (CVD) hospitalizations declined worldwide during the COVID-19 pandemic. It is unclear how shelter-in-place orders affected acute CVD hospitalizations, illness severity, and outcomes. HYPOTHESIS: COVID-19 pandemic was associated with reduced acute CVD hospitalizations (heart failure [HF], acute coronary syndrome [ACS], and stroke [CVA]), and worse HF illness severity. METHODS: We compared acute CVD hospitalizations at Duke University Health System before and after North Carolina's shelter-in-place order (January 1-March 29 vs. March 30-August 31), and used parallel comparison cohorts from 2019. We explored illness severity among admitted HF patients using ADHERE ("high risk": >2 points) and GWTG-HF (">10%": >57 points) in-hospital mortality risk scores, as well as echocardiography-derived parameters. RESULTS: Comparing hospitalizations during January 1-March 29 (N = 1618) vs. March 30-August 31 (N = 2501) in 2020, mean daily CVD hospitalizations decreased (18.2 vs. 16.1 per day, p = .0036), with decreased length of stay (8.4 vs. 7.5 days, p = .0081) and no change in in-hospital mortality (4.7 vs. 5.3%, p = .41). HF hospitalizations decreased (9.0 vs. 7.7 per day, p = .0019), with higher ADHERE ("high risk": 2.5 vs. 4.5%; p = .030), but unchanged GWTG-HF (">10%": 5.3 vs. 4.6%; p = .45), risk groups. Mean LVEF was lower (39.0 vs. 37.2%, p = .034), with higher mean LV mass (262.4 vs. 276.6 g, p = .014). CONCLUSIONS: CVD hospitalizations, HF illness severity, and echocardiography measures did not change between admission periods in 2019. Evaluating short-term data, the COVID-19 shelter-in-place order was associated with reductions in acute CVD hospitalizations, particularly HF, with no significant increase in in-hospital mortality and only minor differences in HF illness severity.

The severity of vasomotor symptoms and number of menopausal symptoms in postmenopausal women and select clinical health outcomes in the Women's Health Initiative Calcium and Vitamin D randomized clinical trial.

OBJECTIVE: This study evaluated whether vasomotor symptom (VMS) severity and number of moderate/severe menopausal symptoms (nMS) were associated with health outcomes, and whether calcium and vitamin D (CaD) modified the risks. METHODS: The Women's Health Initiative CaD study was a double blind, randomized, placebo-controlled trial, which tested 400 IU of 25-hydroxyvitamin-D and 1,000 mg of calcium per day in women aged 50 to 79 years. This study included 20,050 women (median follow-up of 7 y). The outcomes included hip fracture, colorectal cancer, invasive breast cancer, all-cause mortality, coronary heart disease, stroke, cardiovascular death, and total cardiovascular disease (CVD). MS included: hot flashes, night sweats, dizziness, heart racing, tremors, feeling restless, feeling tired, difficulty concentrating, forgetfulness, mood swings, vaginal dryness, breast tenderness, migraine, and waking up several times at night. Associations between VMS severity and nMS with outcomes were tested. RESULTS: No association between VMS severity and any outcome were found. In contrast, nMS was associated with higher stroke (hazard ratio [HR] 1.40 95% confidence interval [CI] 1.04-1.89 for ≥ 2 MS vs none; HR 1.20 95% CI 0.89-1.63 for 1 MS vs none, P trend = 0.03) and total CVD (HR 1.35, 95% CI, 1.18-1.54 for ≥ 2 MS vs none; HR 0.99, 95% CI, 0.87-1.14 for 1 MS vs none P trend < 0.001). CaD did not modify any association. CONCLUSION: Severity of VMS was not associated with any outcome. Having ≥2 moderate or severe MS was associated with an increased risk for CVD. The number of moderate/severe MS may be a marker for higher CVD risk. : Video Summary:http://links.lww.com/MENO/A669.

Video Summary:http://links.lww.com/MENO/A669.

A care pathway for the cardiovascular complications of COVID-19: Insights from an institutional response.

The infection caused by severe acute respiratory syndrome coronavirus-2, or COVID-19, can result in myocardial injury, heart failure, and arrhythmias. In addition to the viral infection itself, investigational therapies for the infection can interact with the cardiovascular system. As cardiologists and cardiovascular service lines will be heavily involved in the care of patients with COVID-19, our division organized an approach to manage these complications, attempting to balance resource utilization and risk to personnel with optimal cardiovascular care. The model presented can provide a framework for other institutions to organize their own approaches and can be adapted to local constraints, resource availability, and emerging knowledge.

Women's Health Initiative clinical trials: potential interactive effect of calcium and vitamin D supplementation with hormonal therapy on cardiovascular disease.

OBJECTIVE: Data in humans and nonhuman primates have suggested a possible synergistic effect of vitamin D and calcium (CaD) and estrogen on the cardiovascular disease (CVD) risk factors. Using randomized trial data we explored whether the effect of menopausal hormone therapy (HT) on CVD events is modified by CaD supplementation. METHODS: A prospective, randomized, double-blind, placebo-controlled trial was implemented among postmenopausal women in the Women's Health Initiative. A total of 27,347 women were randomized to the HT trials (0.625 mg/d of conjugated equine estrogens [CEE] alone for women without a uterus vs placebo; or 0.625 mg of CEE in addition to 2.5 mg of medroxyprogesterone acetate daily [CEE + MPA] for women with a uterus vs placebo). After 1 year, 16,089 women in the HT trial were randomized to the CaD trial and received either 1,000 mg of elemental calcium carbonate and 400 IU of vitamin D3 daily or placebo. The mean (SD) duration of follow-up after CaD randomization was 6.2 (1.3) years for the CEE trial and 4.6 (1.1) years for the CEE + MPA trial. CVD and venous thromboembolism events evaluated in this subgroup analysis included coronary heart disease, stroke, pulmonary embolism, all-cause mortality, plus select secondary endpoints (total myocardial infarction, coronary revascularization, deep venous thrombosis, cardiovascular death, and all CVD events). Time-to-event methods were used and models were fit with a Cox proportional hazards regression model. RESULTS: In the CEE trial, CaD significantly modified the effect of CEE on stroke (P interaction = 0.04). In the CaD-placebo group, CEE's effect on stroke was harmful (hazard ratio [95% confidence interval] = 2.19[1.34-3.58]); however, it was neutral in the CaD-supplement group (hazard ratio [95% confidence interval] = 1.07[0.66-1.73]). We did not observe significant CEE-CaD interactions for coronary heart disease, total CVD events, or any of the remaining endpoints. In the CEE + MPA trial, there was no evidence that the effect of CEE + MPA on any of CVD endpoints was modified by CaD supplementation. CONCLUSIONS: CaD did not consistently modify the effect of CEE therapy or CEE + MPA therapy on CVD events. However, the increased risk of stroke due to CEE therapy appears to be mitigated by CaD supplementation. In contrast, CaD supplementation did not influence the risk of stroke due to CEE + MPA.

Do women prefer care from female or male obstetrician-gynecologists? A study of patient gender preference.

OBJECTIVE: To determine whether men should be encouraged to enter the medical specialty of obstetrics and gynecology. METHODS: A self-administered survey was designed for and distributed to patients (N=264) in 13 obstetrics and gynecology waiting rooms in Connecticut. The survey was used to determine whether there were any patient preferences with regard to the gender of physicians providing obstetric and gynecologic care within this population. In addition, the rationale for any preferences was analyzed. RESULTS: The majority of patients (66.6%) had no gender bias when selecting an obstetrician-gynecologist, and an even larger majority (198, 80.8%) felt that physician gender does not influence quality of care. There was no statistical difference in patient satisfaction based on physician sex. Respondents self-reporting gender bias rarely selected obstetrician-gynecologists based solely on this factor and frequently choose physicians of the sex that was not their indicated preference, suggesting that several factors other than gender preference are more important in physician selection. CONCLUSIONS: The majority of women surveyed did not select their obstetrician-gynecologists based solely on physician gender. Although a small percentage of survey respondents did indicate a gender preference, it rarely influenced physician selection and was only a minor consideration when compared with other desirable physician attributes.

Initial experience with a transcatheter septal closure system for secondary stroke prevention in patients with interatrial septal defects.

BACKGROUND: Percutaneous transcatheter closure of a patent foramen ovale (PFO) has been utilized over the last several years to prevent thromboembolic events in selected patients with a prior cryptogenic stroke. We describe our initial experience at Hartford Hospital with a transcatheter PFO closure system and our multidisciplinary approach. METHODS: From March to November 2002, we performed percutaneous transcatheter closure of a PFO in 16 patients with a prior history of cryptogenic stroke(s) and/or transient ischemic attack using the CardioSEAL Septal Occluder system. All 16 patients had a PFO visualized on their transesophageal echocardiogram (TEE) study, and 15 patients also had an atrial septal aneurysm. PFO closure was performed with a CardioSEAL Septal Occluder in the cardiac catheterization laboratory under general anesthesia with TEE guidance. Following device placement, all patients were discharged on a regimen of aspirin and clopidigrel, with follow-up in the Stroke Clinic. RESULTS: Successful deployment of the septal occluder and effective PFO closure was achieved in all 16 patients with no major procedural or in-hospital complications. Short-term clinical follow-up has demonstrated no recurrent neurologic thromboembolic events, but one patient was rehospitalized for de novo atrial fibrillation. Follow-up transthoracic echocardiographic assessment at three to six months postprocedure, obtained in eight patients thus far, has demonstrated no residual interatrial shunting. CONCLUSION: Our early results suggest that percutaneous PFO closure with the CardioSEAL Septal Occluder system is a safe option for secondary stroke prevention in carefully selected patients with interatrial septal defects and a history of cryptogenic stroke or TIA. Patient selection and the long-term effectiveness and safety of this approach require further assessment.

A 24-hour comparison of serum growth hormone concentrations in patients with heart failure versus healthy controls.

STUDY OBJECTIVE: To compare endogenous serum growth hormone concentrations over a 24-hour period in patients with chronic heart failure (CHF) and matched controls. DESIGN: Prospective, 24-hour, endogenous concentration comparison. SETTING: Hospital research center. PATIENTS: Eight evaluable patients with nonischemic dilated cardiomyopathy and 10 healthy control subjects, matched for age and sex. INTERVENTION: Over a 24-hour period, blood was drawn from the study participants every 20 minutes for determination of growth hormone. MEASUREMENTS AND MAIN RESULTS: For each patient, the area under the concentration-time curve from time 0-24 hours (AUC0-24), maximum concentration (Cmax), and minimum concentration (Cnadir) of growth hormone were determined. The AUC0-24 and Cmax were 74% (p < 0.05) and 62% (p < 0.05) lower in patients with CHF than in controls, respectively. The Cnadir for all participants was 0 microg/L. Variability in growth hormone concentrations over the 24 hours was considerable for all study participants. CONCLUSIONS: Growth hormone concentrations are suppressed over a 24-hour period in patients with CHF versus healthy controls. Variability in levels throughout the day suggests that a single point evaluation cannot be used to determine deficiency or abundance of growth hormone.