Genetic Testing Yield and Clinical Characteristics of Hypertrophic Cardiomyopathy in Understudied Ethnic Groups: Insights From a New Zealand National Registry.

BACKGROUND: Aotearoa/New Zealand has a multiethnic population. Patients with hypertrophic cardiomyopathy (HCM) are enrolled in the national Cardiac Inherited Diseases Registry New Zealand. Here, we report the characteristics of Cardiac Inherited Diseases Registry New Zealand HCM probands with and without pathogenic or likely pathogenic (P/LP) genetic variants for HCM, and assess genetic testing yield and variant spectrum by self-identified ethnicity. METHODS: Probands with HCM and enrolled in Cardiac Inherited Diseases Registry New Zealand who have undergone clinical genetic testing over a 17-year period were included. Clinical data, family history, and genetic test results were analyzed. RESULTS: Of 336 probands, 121 (36%) were women, 220 (66%) were European ethnicity, 41 (12%) were Maori, 26 (8%) were Pacific people, and 49 (15%) were other ethnicities. Thirteen probands (4%) presented with sudden death and 19 (6%) with cardiac arrest. A total of 134 (40%) had a P/LP variant identified; most commonly in the MYBPC3 gene (60%) followed by the MYH7 gene (24%). A P/LP variant was identified in 27% of Maori or Pacific probands versus 43% European or other ethnicity probands (P=0.022); 16% of Maori or Pacific probands had a variant of uncertain significance identified, compared with 9% of European or other ethnicity probands (P=0.092). Women more often had a P/LP variant identified than men (48% versus 35%; P=0.032), and variant-positive probands were younger at clinical diagnosis than variant of uncertain significance/variant-negative probands (39±17 versus 50±17 years; P<0.001) and more likely to have experienced cardiac arrest or sudden death events over their lifetime (P=0.002). CONCLUSIONS: Carriage of a P/LP variant in HCM probands is associated with presentation at younger age, and cardiac arrest or sudden death events. Maori or Pacific probands were less likely to have a P/LP variant identified than European or other ethnicity probands.

Infective endocarditis in patients with rheumatic heart disease: a single-centre retrospective comparative study.

AIMS: We reviewed the baseline characteristics and outcomes of patients with infective endocarditis (IE) and compared those with and without rheumatic heart disease (RHD). METHODS: We retrospectively reviewed patients ≥15 years with IE treated at Auckland City Hospital between January 2016 and December 2018 and excluded device-related IE and complex congenital heart disease. RHD status was based on echocardiographic features or previous history of rheumatic fever with valvular disease. Microbiologic and echocardiographic results, treatment modalities and complications were recorded. Demographics and outcomes were compared based on RHD status. RESULTS: There were 155 patients with IE. Twenty-two had RHD. The mean age at admission was 45 years for RHD patients, which was 19 years younger than for non-RHD patients. There were significantly more Pacific patients with RHD (55% vs 14%). Previous IE and prosthetic valve endocarditis (PVE) were more common in RHD patients (27% vs 5%, and 77% vs 29%, respectively). After a median follow-up of 29 months, there was no significant difference in all-cause mortality between the two groups. However, 25/155 patients (16%) had died from IE-related causes (septic or cardiogenic shock post cardiac surgery, or embolic complications), with a significantly higher mortality in patients with RHD (7/22 (32%) patients, HR: 2.5) on univariate analysis. On multivariable analysis, PVE, heart failure, Staphylococcus aureus infection, diabetes, stroke and cardiac abscess were all associated with increased mortality, whereas RHD was not independently associated with increased mortality. CONCLUSIONS: In this retrospective single-centre audit, patients with RHD experienced IE at a younger age, had a higher incidence of prosthetic valve endocarditis and a prior history of IE. Although there was no difference in all-cause mortality, mortality in patients with RHD was almost exclusively secondary to complications of IE. This highlights the need for prevention strategies against endocarditis in the RHD population, including use of antibiotic prophylaxis¬, accessible dental health care and a high clinical suspicion for IE in RHD by healthcare providers.

Meta-Analysis of Mitral Valve Repair Versus Replacement for Rheumatic Mitral Valve Disease.

BACKGROUND: Rheumatic heart disease remains one of the leading causes of heart valve disease worldwide despite being a preventable condition. Mitral valve repair is superior to replacement in severe degenerative mitral valve disease, however its role in rheumatic valve disease remains controversial. This meta-analysis compared mitral valve repair and replacement in rheumatic heart disease. METHODS: Medline, EMBASE, Cochrane and Scopus were searched from January 1980 to June 2016 for original studies reporting outcomes of both mitral valve repair and replacement in rheumatic heart disease in adults, children or both. Two (2) authors independently assessed studies for inclusion, followed by data extraction and analysis. RESULTS: The search yielded 930 articles, with 98 full-texts reviewed after initial screening and 13 studies subsequently included for analysis, totalling 2,410 mitral valve repairs and 3,598 replacements. Pooled rates and odds ratio (95% confidence interval) for operative mortality of repair versus replacement was 3.2% versus 4.3%, 0.68 (0.50-0.92; p=0.01). Pooled odds ratios (95% confidence interval) were for long-term mortality 0.41 (0.30-0.56; p<0.001); reoperation 3.02 (1.72-5.31; p<0.001); and bleeding 0.26 (0.11-0.63; p=0.003). There was a trend towards lower thrombo-embolism 0.42 (0.17-1.03; p=0.06), and no significant difference in endocarditis (p=0.76), during follow-up. CONCLUSION: Mitral valve repair is associated with reduction in operative and long-term mortality and bleeding, so is recommended in rheumatic mitral valve disease where feasible, but it does entail a higher rate of reoperation during follow-up.

Rheumatic fever recurrences in New Zealand 2010-14.

AIM: To describe the epidemiology and clinical characteristics of recurrences of acute rheumatic fever (ARF) in New Zealand 2010-14. METHOD: Retrospective hospital chart review for ARF with repeat hospital admissions from 2010-14, to identify recurrences of ARF. Definitions of recurrence as per NZ Heart Foundation Guidelines. RESULTS: There were 65 episodes of recurrent ARF among 60 patients. Maori 51%, Pacific 49%. Arthritis and carditis were the most common major manifestations. Median age at recurrence 21.6 years, (8-42 years), with 83% patients over 15 years. There were 841 first episodes of ARF in New Zealand in 2010-4. Overall New Zealand ARF recurrence rate was 7.2% (CI 5.5-8.9%). The recurrence rate was 4% for those under 16 years, 16% for those aged 16-20 and 25% for those >20 years (p<0.05). Seventy-three percent of recurrences occurred in the Auckland region. Recurrences of ARF were strongly associated with RHD progression. CONCLUSION: The risk of recurrence of ARF in New Zealand is low for children. In contrast, recurrences of ARF in New Zealand occur predominantly after age 15, and disproportionately in the Auckland DHBs. Current medical systems and registers may not be meeting the needs of adolescents and adults requiring secondary prophylaxis.

Valve-in-Valve in a Flail Bioprosthetic Mitral Valve With Endocarditis Using a Novel Embolic Protection Device.

A 79-year-old woman presented in cardiogenic shock with a flail bioprosthetic mitral valve leaflet and Staphylococcus aureus endocarditis. In the absence of other viable options, transfemoral valve-in-valve transcatheter mitral valve replacement was performed with a novel embolic protection device, resulting in trace mitral regurgitation and no neurologic complications. (Level of Difficulty: Advanced.).

The not so innocent heart murmur: a 5-year experience.

BACKGROUND: Auckland City Hospital (ACH) established a Heart Murmur Clinic (HMC) with the aim of providing prompt assessment of patients with asymptomatic systolic murmurs. This may lead to early intervention and improved outcomes if significant structural heart disease is detected and reassurance if no significant findings are found. Similar clinics for children have proven beneficial; the benefit of a HMC in an adult population has been difficult to determine. AIM: To review the clinical demographics and echocardiographic information of patients presenting to our HMC, to assess what proportion of significance structural heart disease had and determine the common structural abnormalities in this population. METHODS: This is a retrospective review of patients aged ≥15 years presenting to our HMC between March 2010 and December 2015 with an asymptomatic systolic murmur. Patients with previous cardiac surgery or known congenital or valvular heart disease were excluded. RESULTS: A total of 1221 patients was reviewed over the 5-year period; 980 underwent echocardiography. Significant cardiac disease was detected in 156 patients, with 23 patients requiring surgical intervention over the 5-year period. Significant aortic stenosis (n = 43) and mitral regurgitation (n = 48) were the most common pathologies. Patients > 65 years were more likely to have structural heart disease (16% vs 11%, P < 0.05). CONCLUSION: Establishing a HMC has allowed the screening of a large number of patients who would otherwise have low priority for assessment. We have identified a large proportion with significant structural disease, which has allowed for early surgical intervention when appropriate and may potentially result in improved patient outcomes.

Right Ventricular Assessment in Adult Congenital Heart Disease Patients with Right Ventricle-to-Pulmonary Artery Conduits.

BACKGROUND: There is little data on right ventricular (RV) remodeling patterns in complex congenital heart disease (CHD) patients with right ventricle to pulmonary artery (PA) conduits, and novel RV imaging modalities have not been explored in this population. Knowledge of the RV remodeling process is an important first step to future understanding and tracking of the RV response to pressure and volume overload in this diverse population. Three-dimensional knowledge-based reconstruction (3DKBR) derived from two-dimensional transthoracic echocardiography (TTE-3DKBR) is a novel approach to RV assessment. The aims of this study were twofold: (1) to assess the feasibility and accuracy of 3DKBR in patients with CHD with RV to PA conduits and (2) to characterize the three-dimensional shape of the RV across the spectrum of CHD with RV to PA conduits. METHODS: Seventeen patients with tetralogy of Fallot, pulmonary atresia with ventricular septal defect, or truncus arteriosus (mean age, 29 ± 8 years; 24% women) and a conduit referred for cardiac magnetic resonance imaging (CMR) were prospectively recruited and underwent TTE-3DKBR. TTE-3DKBR echocardiographic image acquisition was performed using a standard ultrasound scanner linked to a Ventripoint Medical Systems unit. The surface RV volumetric reconstruction was performed by transmitting two-dimensional data points to an online database and comparing these with a lesion-specific catalog to derive the RV reconstruction. Parameters analyzed were end-diastolic volume (EDV), end-systolic volume, and ejection fraction. Intertechnique agreement was assessed using Pearson's correlation analysis, coefficients of variation, and Bland-Altman analysis. Three-dimensional shape comparisons of RV surface reconstructions were performed via automated validation testing of CMRs from 43 patients (mean age, 30 ± 8 years; 32% women) with RV to PA conduits (tetralogy of Fallot, n = 15; pulmonary atresia, n = 19; and truncus arteriosus, n = 9) distinct from patients in the 3DKBR comparison. RESULTS: There was good correlation and agreement between the two modalities: EDV, R = 0.77, P = .0004; end-systolic volume, R = 0.93, P < .0001; ejection fraction, R = 0.75, P < .0005. On Bland-Altman analyses, CMR EDV was slightly larger TTE-3DKBR, while EF was slightly higher by 3DKBR. Qualitative and quantitative assessment both demonstrated RV shape diversity based on surface reconstructions. CONCLUSION: This study demonstrates that TTE-3DKBR is an alternative technology that can be used to assess the RV in patients with complex CHD with a conduit. A novel method was used to compare RV shapes in this important population, and our results draw specific attention to the fact that the RV both within and outside diagnostic groups has very different unpredictable shapes and should not be treated equally. Our findings should set into motion future work focused on indices of RV shape and their impact on overall RV function and clinical outcomes, hence defining optimal timing of conduit revision, which at the current time is very unclear.

Can we predict sudden cardiac death in long-term survivors of atrial switch surgery for transposition of the great arteries?

OBJECTIVE: This study aims to identify predictors of sudden cardiac death (SCD) in patients with transposition of the great arteries (TGA) who have undergone atrial baffle surgery with the Mustard or Senning operation. BACKGROUND: Patients with TGA and previous atrial baffle surgery are known to be at increased risk of SCD. Despite this, indications for insertion of an implantable cardiac defibrillator for primary prevention have not been established. METHODS: Eighty-nine patients with a diagnosis of TGA and previous Mustard or Senning repair were identified. Medical records were reviewed for SCD, aborted SCD, implantation of cardiac defibrillator (ICD), and use of cardiac medications. Clinically significant events (heart failure admissions, documented arrhythmias, and insertion of a pacemaker) were ascertained, and results of echocardiograms were explored. RESULTS: There were five SCDs in our population, and five patients underwent a primary prevention ICD insertion, with no subsequent sustained ventricular arrhythmia or aborted SCD. Patients who suffered SCD had undergone surgery at an older age (median 53 months vs. 14 months) in a slightly earlier era (median year of operation 1971 vs. 1975). Atrial arrhythmias requiring treatment were documented in 100% of the SCD and in 29% of the no SCD patients. CONCLUSIONS: Criteria for insertion of primary prevention implantable cardiac defibrillators postatrial baffle surgery remain to be established. In the SCD subgroup, surgery at an older age, earlier era of surgical repair, and history of atrial arrhythmia appear to convey an increased risk of sudden death.

Caseous calcification of the mitral annulus.

A 61-year-old asymptomatic woman was referred for echocardiography to evaluate recently detected systolic murmur. Transthoracic echocardiography revealed an echodense obstructive mass in the left ventricular outflow tract of unclear origin. Subsequent transesophageal echo suggested an intracardiac calcified tumor and recommended surgical excision. Contrast-enhanced cardiac computed tomography (CT) confirmed a well-defined lobulated mass adherent to the anterior mitral valve leaflet, the non-enhanced scout view revealed marked hyper-attenuation confirming diffuse calcification. Caseous calcification was diagnosed and surgery was deferred. Caseous calcification is typically benign and most commonly involves the posterior mitral annulus. Our patient displayed an atypical location of exuberant mitral annular calcification.

Multidetector CT predictors of prosthesis-patient mismatch in transcatheter aortic valve replacement.

BACKGROUND: Prosthesis-patient mismatch (PPM) is a predictor of mortality after aortic valve replacement (AVR). OBJECTIVE: We examined whether accurate 3-dimensional annular sizing with multidetector CT (MDCT) is predictive of PPM after transcatheter AVR (TAVR). METHODS: One hundred twenty-eight patients underwent MDCT then TAVR. Moderate PPM was defined as an indexed effective orifice area ≤0.85 cm²/m² and severe ≤0.65 cm²/m². MDCT annular measurements (area, short and long axis) were compared with the size of the selected transcatheter heart valve (THV) to obtain (1) the difference between prosthesis size and CT-measured mean annular diameter and (2) the percentage of undersizing or oversizing (calculated as 100 × [MDCT annular area--THV nominal area]/THV nominal area). In addition, the MDCT annular area was indexed to body surface area. These measures were evaluated as potential PPM predictors. RESULTS: We found that 42.2% of patients had moderate PPM and 9.4% had severe PPM. Procedural characteristics and in-hospital outcomes were similar between patients with or without PPM. THV undersizing of the mean aortic annulus diameter was not predictive of PPM (odds ratio [OR], 0.84; 95% CI, 0.65-1.07; P = .16; area under the receiver-operating characteristic curve [AUC], 0.58). THV undersizing of annular area was not predictive of PPM (OR, 0.96; 95% CI, 0.80-1.16; P = .69; AUC, 0.52). Indexed MDCT annular area was, however, predictive of PPM (OR, 0.24; 95% CI, 0.10-0.59; P < .001; AUC, 0.66). CONCLUSIONS: PPM is frequent after TAVR. Appropriate annular oversizing does not reduce the rate or severity of PPM. Patient annulus size mismatch, identified by indexed MDCT annular area, is a significant predictor of PPM.

Impact of low flow on the outcome of high-risk patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: This study sought to assess the impact of baseline left ventricular (LV) outflow, LV ejection fraction (LVEF), and transvalvular gradient on outcomes following transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis (AS). BACKGROUND: Low flow (i.e., reduced stroke volume index [SVi]) can occur with both reduced and preserved LVEF. Low flow is often associated with low gradient despite severe stenosis and with worse outcomes following surgical aortic valve replacement. However, there are few data about the impact of low flow on outcomes following TAVR. METHODS: We retrospectively analyzed the clinical, Doppler-echocardiographic, and outcome data prospectively collected in 639 patients who underwent TAVR for symptomatic severe AS in 2 Canadian centers. RESULTS: In this cohort, 334 (52.3%) patients had a low flow (SVi <35 ml/m(2)) and these patients had increased 30-day mortality (11.4 vs. 5.9%, p = 0.01), 2-year all-cause mortality (35.3 vs. 30.9%, p = 0.005), and 2-year cardiovascular mortality (25.7 vs. 16.8%, p = 0.01) compared with patients with normal flow. Reduced flow was an independent predictor of 30-day mortality (odds ratio: 1.94, p = 0.026), cumulative all-cause mortality (hazard ratio: 1.27 per 10 ml/m(2) SVi decrease, p = 0.016), and cumulative cardiovascular mortality (hazard ratio: 1.29 per 10 ml/m(2) decrease, p = 0.04). Despite significant association in univariable analyses, low LVEF and low mean gradient were not found to be independent predictors of outcomes in multivariable analyses. CONCLUSIONS: Low flow but not low LVEF or low gradient is an independent predictor of early and late mortality following TAVR in high-risk patients with severe AS. SVi should be integrated in the risk stratification process of these patients.

The impact of integration of a multidetector computed tomography annulus area sizing algorithm on outcomes of transcatheter aortic valve replacement: a prospective, multicenter, controlled trial.

OBJECTIVES: This study prospectively investigated the impact of integration of a multidetector computed tomography (MDCT) annular area sizing algorithm on transcatheter aortic valve replacement (TAVR) outcomes. BACKGROUND: Appreciation of the 3-dimensional, noncircular geometry of the aortic annulus is important for transcatheter heart valve (THV) sizing. METHODS: Patients being evaluated for TAVR in 4 centers underwent pre-procedural MDCT. Recommendations for balloon-expandable THV size selection were based on an MDCT sizing algorithm with an optimal goal of modest annulus area oversizing (5% to 10%). Consecutive patients who underwent TAVR with the algorithm (MDCT group) were compared with consecutive patients without the algorithm (control group). The primary endpoint was the incidence of more than mild paravalvular regurgitation (PAR), and the secondary endpoint was the composite of in-hospital death, aortic annulus rupture, and severe PAR. RESULTS: Of 266 patients, 133 consecutive patients underwent TAVR (SAPIEN XT THV) in the MDCT group and 133 consecutive patients were in the control group. More than mild PAR was present in 5.3% (7 of 133) of the MDCT group and in 12.8% (17 of 133) in the control group (p = 0.032). The combined secondary endpoint occurred in 3.8% (5 of 133) of the MDCT group and in 11.3% (15 of 133) of the control group (p = 0.02), driven by the difference of severe PAR. CONCLUSIONS: The implementation of an MDCT annulus area sizing algorithm for TAVR reduces PAR. Three-dimensional aortic annular assessment and annular area sizing should be considered for TAVR.

Does pregnancy contribute to systemic right ventricular dysfunction in adults with an atrial switch operation?

BACKGROUND: To determine whether pregnancy might impact adversely on long-term outcomes in adults post an atrial switch repair on the background of data demonstrating an increased rate of heart failure and death in these adults with systemic right ventricles. METHODS: We retrospectively analysed our adult population with an atrial switch repair for transposition of the great arteries to see whether any differences in outcomes (sudden cardiac death, heart failure admissions, use of heart failure medications) existed between women who had and women who had not undergone pregnancy. Controls from the remaining population (transposition of the great arteries and atrial switch operation women) were elected as long as their year of birth fell into the year of birth range seen in the patient group. RESULTS: In women with transposition of the great arteries who have had an atrial switch repair, the long-term occurrence of sudden cardiac death and clinical heart failure (defined as a need for prescription of anti-failure medications or heart failure admissions) appears to be increased. CONCLUSION: Pregnancy may have an adverse effect on long-term outcomes in women with systemic right ventricles.

3-dimensional aortic annular assessment by multidetector computed tomography predicts moderate or severe paravalvular regurgitation after transcatheter aortic valve replacement: a multicenter retrospective analysis.

OBJECTIVES: This study sought to analyze multidetector computed tomography (MDCT) 3-dimensional aortic annular dimensions for the prediction of paravalvular aortic regurgitation (PAR) following transcatheter aortic valve replacement (TAVR). BACKGROUND: Moderate or severe PAR after TAVR is associated with increased morbidity and mortality. METHODS: A total of 109 consecutive patients underwent MDCT pre-TAVR with a balloon expandable aortic valve. Differences between transcatheter heart valve (THV) size and MDCT measures of annular size (mean diameter, area, and circumference) were analyzed concerning prediction of PAR. Patients with THV malposition (n = 7) were excluded. In 50 patients, MDCT was repeated after TAVR to assess THV eccentricity (1 - short diameter/long diameter) and expansion (MDCT measured THV area/nominal THV area). RESULTS: Moderate or severe PAR (13 of 102) was associated with THV undersizing (THV diameter - mean diameter = -0.7 ± 1.4 mm vs. 0.9 ± 1.8 mm for trivial to mild PAR, p < 0.01). The difference between THV size and MDCT annular size was predictive of PAR (mean diameter: area under the curve [AUC]: 0.81, 95% confidence interval [CI]: 0.68 to 0.88; area: AUC: 0.80, 95% CI: 0.65 to 0.90; circumference: AUC: 0.76, 95% CI: 0.59 to 0.91). Annular eccentricity was not associated with PAR (AUC: 0.58, 95% CI: 0.46 to 0.75). We found that 35.3% (36 of 102) and 45.1% (46 of 102) of THVs were undersized relative to the MDCT mean diameter and area, respectively. THV oversizing relative to the annular area was not associated with THV eccentricity or underexpansion (oversized vs. undersized THVs; expansion: 102.7 ± 5.3% vs. 106.1 ± 5.6%, p = 0.03; eccentricity: median: 1.7% [interquartile range: 1.4% to 3.0%] vs. 1.7% [interquartile range: 1.1% to 2.7%], p = 0.28). CONCLUSIONS: MDCT-derived 3-dimensional aortic annular measurements are predictive of moderate or severe PAR following TAVR. Oversizing of THVs may reduce the risk of moderate or severe PAR.

Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial mechanical function after reversion of atrial arrhythmias to sinus rhythm: reversal of tachycardia-mediated atrial cardiomyopathy with fish oils.

BACKGROUND: Atrial mechanical stunning is a form of tachycardia-mediated atrial cardiomyopathy that manifests after reversion of persistent atrial arrhythmias to sinus rhythm. OBJECTIVES: This study sought to examine whether chronic omega-3 polyunsaturated fatty acid supplementation with fish oils can reverse atrial mechanical stunning. METHODS: Patients undergoing reversion of persistent atrial fibrillation (AF) or atrial flutter (AFL) to sinus rhythm were randomized to a control group (n = 26) or an omega-3 group (n = 23). The latter were prescribed 6 g/day of fish oil for ≥1 month prior to the procedure. Parameters of left atrial appendage function were compared immediately before and immediately after reversion. RESULTS: After fish oil intake for a mean of 70 days, the following were noted favoring the omega-3 group among both AF and AFL patients: (1) 2-fold higher serum omega-3 levels (P < .001), (2) less mean decrease in emptying velocity (e.g., AF: 8% vs. 32%, P = .02), (3) less mean decrease in appendage emptying fraction (e.g., AFL: 7% vs. 60%, P = .002), (4) lower incidence of new or increased spontaneous echocardiographic contrast (e.g., AF: 11% vs. 62.5%, P = .003), and (5) lower incidence of atrial mechanical stunning (e.g., AFL: 20% vs. 100%, P = .001). Omega-3 intake conferred protection against stunning in a multivariable analysis (odds ratio 0.18, P = .02). CONCLUSION: Chronic fish oil ingestion in humans attenuates atrial mechanical stunning after reversion of atrial arrhythmias to sinus rhythm. This suggests that fish oils may target or even reverse underlying cellular and/or structural remodeling that occurs in response to persistent atrial arrhythmias.