Citations

Introduction: Mitral paravalvular leak (PVL) occurs in 7-17% of patients after mitral valve surgery. The percutaneous closure of these defects has become a novel treatment to prevent repeat operations. Hypothesis: We hypothesize flow dynamics correlate with clinical outcomes of patients undergoing percutaneous mitral PVL closure. Methods: We retrospectively studied 148 patients who underwent percutaneous PVL closure between 2004 and 2014 at Mayo Clinic. We measured the continuous wave (CW) Doppler time velocity integral (TVI), E velocity (as a surrogate for V wave) across the mitral valve and left ventricular ejection fraction (LVEF) by transthoracic echocardiogram within 7 days before and after PVL closure. We identified patients as non-responders if there was moderate to severe residual mitral regurgitation. t-Test was used for continuous variables and Fisher exact test was used mortality. Results: Overall, the mean CW TVI was markedly reduced by PVL closure (93±14 vs. 58±5cm, p<0.02). The E velocity also decreased after closure (3.1±0.4 vs. 1.9±0.1m/sec, p<0.04). LVEF, however, was reduced after PVL closure (62%±2 vs. 53%±1.5, p<0.02). Among non-responders (34/148 patients), there was no significant difference between the CW and E velocity before and after the procedure (CW TVI: 96±16 vs. 83+13cm, E velocity: 2.5±0.5 vs. 2.3±0.3m/sec, p=NS). The estimated 5-year mortality of patients with no or mild residual mitral regurgitation was markedly lower compared to non-responders, 43% vs 71%, p<0.05. Conclusions: The flow dynamics across the mitral valve immediately after PVL closure may correlate with long term clinical outcomes. Real time assessment of flow by transesophageal echocardiogram can be used to guide the extent of PVL closure required to change the long term clinical outcomes. Further validation and prospective studies are required.

Diastolic dysfunction plays a critical role in the pathophysiology of producing signs and symptoms of heart failure. Heart failure with a normal ejection fraction (HFnlEF) is one of the leading causes of hospital admissions today and is associated with significant morbidity and mortality. It is thus important to understand the pathophysiology of diastolic dysfunction, which itself is a complex series of multiple interrelated events, including relaxation, suction, ventricular interaction, ventricular arterial coupling, pericardial restraint, and myocardial viscoelastic forces. It was difficult for the clinician to understand “diastology” in the past. Initial studies were limited to complex equations derived from animal models and were difficult to apply to patient care. The development of radionuclide angiography and Doppler echocardiography allowed noninvasive rapid assessment of volumetric filling and flow velocity curves, which began to provide insight into the complex process of diastolic filling for the clinician. As our understanding of diastology evolved over the past 2 decades, it has become clear that we now need to pursue new areas to understand this fascinating subject and apply it to patient care. These areas include the underlying mechanism HFnlEF (ventricular-vascular coupling versus true myocardial stiffness), relationship of rest versus exercise hemodynamics, and the complex ventricular fiber “twisting and shortening” of both contraction and relaxation.

Background. Apical hypertrophic cardiomyopathy (AHCM) has been considered a ``benign” form of HCM in Asian and non-Asian patients (pt). However, data on long-term outcome of pt with AHCM are limited. The purpose of this study was to determine the natural history of pt with AHCM followed at a tertiary referral center in North America. Methods. Between July 1976 and September 2006, 193 pt with the diagnosis of AHCM were seen at the Hypertrophic Cardiomyopathy Clinic. The last echocardiographic exam was reviewed in all pt. Follow-up data were obtained where possible (clinic visit). Results. Mean age at diagnosis 56±17 years, mean age at first presentation at our center was 58±17 years. Symptoms included chest pain in 69 pt (36 %), and exertional dyspnea ≥NYHA II in 97 pt (50 %). A family history of either HCM and/or sudden cardiac death was reported by 36 pt (19 %). Coronary artery disease was proven in 40 pt (21 %). Median follow up was 50 months (1–318) and obtained in 124 pt (64 %). The following events were reported at the last clinic visit: heart failure in =5 pt, syncope in =0 pt, ventricular tachycardia in =7 pt, ICD implantation in 22 pt, and stroke in 22 pt. Death from all causes occurred in 51 of 193 pt (26 %) at a mean age of 72 years (14–78). Kaplan-Meier survival analysis was used to examine survival from all causes of death since first presentation. Observed survival in patients with AHCM was significantly less than expected in an age- and gender matched Minnesota white population (p=0.009). The observed survival at 5, 10 and 15 years was 87 %, 82 %, and 57 % respectively, while the expected survival for these time points was 91 %, 81 %, and 72 %. Conclusions. AHCM in this predominantly North American patient population is associated with an increased mortality. Patients with AHCM have a high incidence of significant cardiovascular symptoms and ventricular arrhythmias. As the disease is less benign than previously suspected, careful longitudinal care by a cardiologist is warranted.

Background: Exercise normally enhances LV relaxation with minimal change in filling pressure (P). We hypothesize that exercise in hypertensive (HTN) patients increases LV diastolic P through a direct effect on relaxation and ventricular-vascular coupling. Methods: Patients (n=21) with HTN, normal EF, and no coronary disease underwent simultaneous micromanometer LV P and echo-Doppler measurements at rest and with low level supine exercise (12 bicycle; 9 arm weight). Continuous volume (V) was obtained from mitral Doppler inflow and end-diastolic (ED) and end-systolic (ES) V from 2-D echo. Relaxation-corrected LV diastolic P was used for PV relationship P = α.e β*V ; to account for covariance in α and β, LV capacitance (EDV 20 = Ln[20mmHg/α]/β) was reported. Single beat method was used for LV ES elastance (Ees). Group 1 did not increase mean LV diastolic P (mDP) with exercise, Group 2 increased mDP >6mmHg. Results: LV diastolic P and arterial and LV ES elastance increased with exercise; EDV was stable; EDV 20 decreased. Compared to Group 1, Group 2 had a greater exercise-induced increase in afterload, associated with increase in LV minimal P and impaired augmentation of relaxation rate (Table & Figure ). Conclusions: In patients with HTN, impairment of ventricular relaxation plays a major role in causing LV filling P increase with exercise, which is related to ventricular-vascular coupling.

Introduction: Presence of subclinical left ventricle (LV) dysfunction may influence outcomes after percutaneous mitral balloon valvotomy (PMBV), but cannot be detected by conventional echocardiography. Hypothesis: Preprocedure LV global longitudinal strain (GLS) by speckle tracking TTE detects subclinical LV dysfunction and predicts long-term outcome after successful PMVB. Methods: Consecutive patients undergoing PMBV between 2003-2011 who had comprehensive baseline TTE were included. Patients with suboptimal immediate results (repeat PMBV or mitral surgery within first 6 months) and those with suboptimal TTE strain were excluded. LV strain was analyzed with commercial software (Syngo VVI), and GLS averaged from 18 segments. The primary end point was all-cause mortality. Secondary end point was the composite of death and mitral valve reintervention. Results: Of 110 patients screened, 29 (26%) had unsuitable strain imaging, and 8 (7%) had poor immediate results, leaving 73 in the final cohort. Median follow-up was 3.7 years (interquartile range 1.3-7.2). There were 10 deaths (14%) and 25 late mitral valve interventions (34%). Univariate predictors of death were GLS, age, EF, stroke volume, pulmonary artery pressure, mitral valve area and coronary artery disease. In a multivariate Cox model, GLS was the strongest predictor of death after adjustment for age [HR=1.40 (1.09-1.84), P=0.008]. For the composite endpoint, GLS, mitral valve gradient, and invasively mean left atrial pressure were univariate predictors of death or reintervention. At multivariate analysis, GLS was the sole predictor of events [HR=1.17 (1.01-1.34), P=0.03]. Event-free survival is shown in figure. Intra and inter observer intra-class correlation for strain analysis was 0.87 (0.66-0.96) and 0.84 (0.53-0.95), respectively. Conclusions: GLS is a powerful predictor of long-term outcome after PMVB and appears to have an incremental prognostic value over traditional parameters.

Background Contemporary nationwide data on the use, predictors, and outcomes of mechanical valve replacement in patients less than 70 years of age are limited. Methods and Results We identified hospitalizations for aortic valve replacement (AVR) or mitral valve replacement (MVR) in the Nationwide Inpatient Sample between January 1, 2008, and December 31, 2017. The study's end points included predictors of mechanical valve replacement and risk‐adjusted in‐hospital mortality. Among 253 100 hospitalizations for AVR, the use rate of mechanical prosthesis decreased from 45.3% in 2008 to 17.0% in 2017. Among 284 962 hospitalizations for MVR, mechanical prosthesis use decreased from 59.5% in 2008 to 29.2% in 2017 ( P for trend<0.001). In multilogistic regression analyses, female sex, prior sternotomy, prior defibrillator, and South/West geographic location were predictive of mechanical valve use. The presence of bicuspid valve was a negative predictor of mechanical AVR (odds ratio [OR], 0.68; 95% CI, 0.66–0.69; P <0.001), whereas mitral stenosis was associated with higher mechanical MVR (OR, 1.28; 95% CI, 1.22–1.33; P <0.001). Unadjusted in‐hospital mortality decreased over time with AVR but not with MVR, regardless of prosthesis choice. Using years 2008 and 2009 as a reference, risk‐adjusted mortality also decreased over time with AVR but did not decrease after MVR. Conclusions There is a substantial decline in the use of mechanical valve replacement among patients aged ≤70 years in the United States. Long‐term durability data on bioprosthetic valve replacement are needed to better define the future role of mechanical valves in this age group.

Abstract Aims Circulating blood volume is functionally divided between the unstressed volume, which fills the vascular space, and stressed blood volume (SBV), which generates vascular wall tension and intravascular pressure. With decreases in venous capacitance, blood functionally shifts to the SBV, increasing central venous pressure and pulmonary venous pressures. Obesity is associated with both elevated venous pressure and heart failure with preserved ejection fraction (HFpEF). To explore the mechanisms underlying this association, we evaluated relationships between blood volume distribution, venous compliance, and body mass in patients with and without HFpEF. Methods and results Subjects with HFpEF ( n = 62) and non‐cardiac dyspnoea (NCD) ( n = 79) underwent invasive haemodynamic exercise testing with echocardiography. SBV was estimated (eSBV) from measured haemodynamic variables fit to a comprehensive cardiovascular model. Compared to NCD, patients with HFpEF displayed a leftward‐shifted central venous pressure–dimension relationship, indicating reduced venous compliance. eSBV was 81% higher at rest and 69% higher during exercise in HFpEF than NCD (both P < 0.0001), indicating reduced venous capacitance. Despite greater augmented eSBV with exercise, the increase in cardiac output was reduced in HFpEF, suggesting operation on the plateau of the Starling curve. Exercise eSBV was directly correlated with higher body mass index (r = 0.77, P < 0.0001) and inversely correlated with right ventricular–pulmonary arterial coupling (r = −0.57, all P < 0.0001). Conclusions Patients with HFpEF display reductions in systemic venous compliance and increased eSBV related to reduced venous capacitance, abnormalities in right ventricular–pulmonary artery interaction, and increased body fat. These data provide new evidence supporting an important role of venous dysfunction in obesity‐related HFpEF and suggest that therapies that improve venous function may hold promise to improve clinical status in this cohort.

AbstractBiallelic loss‐of‐function variants in the thrombospondin‐type laminin G domain and epilepsy‐associated repeats (TSPEAR) gene have recently been associated with ectodermal dysplasia and hearing loss. The first reports describing a TSPEAR disease association identified this gene is a cause of nonsyndromic hearing loss, but subsequent reports involving additional affected families have questioned this evidence and suggested a stronger association with ectodermal dysplasia. To clarify genotype–phenotype associations for TSPEAR variants, we characterized 13 individuals with biallelic TSPEAR variants. Individuals underwent either exome sequencing or panel‐based genetic testing. Nearly all of these newly reported individuals (11/13) have phenotypes that include tooth agenesis or ectodermal dysplasia, while three newly reported individuals have hearing loss. Of the individuals displaying hearing loss, all have additional variants in other hearing‐loss‐associated genes, specifically TMPRSS3, GJB2, and GJB6, that present competing candidates for their hearing loss phenotype. When presented alongside previous reports, the overall evidence supports the association of TSPEAR variants with ectodermal dysplasia and tooth agenesis features but creates significant doubt as to whether TSPEAR variants are a monogenic cause of hearing loss. Further functional evidence is needed to evaluate this phenotypic association.