Pathogenic BCS1L Mutation Resulting in Hypertrophic Cardiomyopathy: A Unique Presentation of Nuclear Mitochondrial Disease.

A 21-year-old man with sensorineural hearing loss and glaucoma presented with severely limited exercise capacity since childhood. He was found to have biventricular concentric hypertrophy with greatest wall thickening at the posterior and lateral walls of the left ventricle apex (1.7 cm) and the free wall of the right ventricle (1.1 cm). There was no inducible left ventricular outflow tract obstruction. Metabolic testing revealed marked lactic aciduria (1,650.1 µmol/mmol creatinine) and plasma lactate (3.9 mmol/L). A sarcomeric hypertrophic cardiomyopathy gene panel was unremarkable, but mitochondrial gene analysis revealed a homozygous c.385G>A (p.Gly129Arg) pathogenic mutation in the BCS1L gene. This gene is responsible for an assembly subunit of cytochrome complex III in the respiratory transport chain and is the rarest respiratory chain defect. This gene has not frequently been implicated in cardiomyopathy. Mitochondrial hypertrophic cardiomyopathy is more rare than hypertrophic cardiomyopathy resulting from sarcomeric mutations and is more likely to be symmetric, less frequently results in left ventricular outflow tract obstruction, and is more likely to progress to dilated cardiomyopathy. Evidence-based screening protocols have not been established; treatment follows guideline-directed medical therapy for congestive heart failure, including evaluation for heart transplantation. This report expands the phenotype of the BCS1L mutation and suggests that affected patients may need screening for underlying cardiomyopathy.

Large Left Ventricular Pseudoaneurysm Presenting as an Embolic Stroke After a "Silent" Myocardial Infarction.

A 72-year-old woman with no history of coronary artery disease presented with an acute left middle cerebral artery stroke and was found to have a large left ventricular pseudoaneurysm measuring 8.7 × 7.6 cm and 2 large left ventricular thrombi, the source of her systemic embolization. Despite initial medical management, she developed refractory New York Heart Association functional class III heart failure, uncontrolled atrial fibrillation, and further enlargement of her pseudoaneurysm to 5.5 × 10.6 × 9.2 cm. She underwent urgent aneurysmectomy. Left ventricular pseudoaneurysms are rare and most commonly occur following an acute myocardial infarction when a ventricular free-wall rupture is contained by pericardium or thrombi. Historically, left ventricular angiography displaying a lack of an overlying coronary artery was the gold standard for diagnosis. Now, noninvasive imaging such as computed tomography, magnetic resonance imaging, and echocardiogram with ultrasound-enhancing agent, are reliable diagnostic tools. They can distinguish a pseudoaneurysm from a true left ventricular aneurysm using characteristic findings such as a narrow aneurysm neck, bidirectional doppler flow between the pseudoaneurysm and the left ventricle, and abrupt changes in the cardiac wall structures. Progressive dilation, wall thinning, and dyskinesis can result in refractory heart failure, arrhythmias, and thrombi formation from venous stasis. Pseudoaneurysms have a 30% to 45% risk of rupture and can be treated with left ventricular aneurysmectomy.

Predictors and outcome of electrical storm-induced cardiogenic shock.

AIM: Limited information is available about the short- and long-term outcomes in electrical storm (ES)-induced cardiogenic shock (CS) and its predictors. METHODS AND RESULTS: This is a retrospective, single-centre cohort study of consecutive patients with ES admitted to the Cardiac Intensive Care Unit between 2015 and 2020. The proportion of ES patients who developed CS was adjudicated, and clinical predictors of in-hospital ventricular arrhythmia (VA)-related mortality and 1-year all-cause mortality were investigated. Of the 214 patients with ES, 33.6% developed CS. Left-ventricular ejection fraction, admission lactate, absence of an implantable cardioverter defibrillator, and admission central venous pressure were independently associated with development of CS (P < 0.03 for all). Based on these variables, a FLIC score was developed (https://riskcalc.org/FLICscore/) to predict ES-induced CS [area under the curve (AUC) = 0.949, with AUC = 0.954 in a validation cohort, both P < 0.001]. Patients who developed CS had a 11.3-fold [95% confidence interval (CI) 2.7-12.8] increased odds for in-hospital VA-related mortality and 9.4-fold (95% CI 4.0-22.4) increased odds for in-hospital all-cause mortality. A FLIC score above 0.62 was associated with a 6.2- and 5.8-fold increased odds for respectively similar endpoints. Patients with ES-induced CS received more treatment modalities to manage the ES (4.5 ± 1.8 vs. 2.3 ± 1.2, P < 0.001) and had longer length of stay [14 (8-27) vs. 8 (5-13), P < 0.001] than patients without CS. Interestingly, if patients with ES-induced CS survived to discharge, their outcomes were similar to those without CS at 1 year. CONCLUSION: Cardiogenic shock in ES is a frequent and potentially life-threatening complication with high short-term mortality. A novel risk score could identify patient at risk, generating a potential for early risk-based interventions.

Systematic Approach to High Implantation of SAPIEN-3 Valve Achieves a Lower Rate of Conduction Abnormalities Including Pacemaker Implantation.

BACKGROUND: The conventional method of implanting balloon-expandable SAPIEN-3 (S3) valve results in a final 70:30 or 80:20 ratio of the valve in the aorta:left ventricular outflow tract with published rates of permanent pacemaker around 10%. We sought to evaluate whether higher implantation of S3 reduces conduction abnormalities including the need for permanent pacemaker. METHODS: We included consecutive patients who underwent transfemoral transcatheter aortic valve replacement using S3 between April 2015 and December 2018 and compared outcomes with typical valve deployment strategy to our more contemporary high deployment technique (HDT). We excluded patients with nontransfemoral access or valve-in-valve. RESULTS: Among 1028 patients, HDT was performed in 406 patients (39.5%). Mean implantation depth under the noncoronary cusp was significantly smaller with HDT compared with conventional technique (1.5±1.6 versus 3.2±1.9 mm; P<0.001). Successful implantation was achieved in 100% of the patients in both groups with no cases of conversion to open heart surgery, second valve implantation within the first transcatheter aortic valve replacement, or coronary occlusion during transcatheter aortic valve replacement. One patient (0.2%) had valve embolization with HDT (P=0.216). Thirty-day permanent pacemaker rates were lower with HDT (5.5% versus 13.1%; P<0.001), as were rates of complete heart block (3.5% versus 11.2%; P<0.001) and new-onset left bundle branch block (5.3% versus 12.2%; P<0.001). There were no differences in mild (16.5% versus 15.9%; P=0.804), or moderate-to-severe aortic regurgitation (1% versus 2.7%; P=0.081) at 1 year. HDT was associated with slightly higher 1-year mean gradients (13.1±6.2 versus 11.8±4.9 mm Hg; P=0.042) and peak gradients (25±11.9 versus 22.5±9 mm Hg; P=0.026). However, Doppler velocity index was similar (0.47±0.15 versus 0.48±0.13; P=0.772). CONCLUSIONS: Our novel technique for balloon-expandable S3 valve positioning consistently achieves higher implantation resulting in substantial reduction in conduction abnormalities and permanent pacemaker requirement after transcatheter aortic valve replacement without compromising procedural safety or valve hemodynamics. Operators should consider this as an important technique to improve patient outcomes.

Impact of baseline conduction abnormalities on outcomes after transcatheter aortic valve replacement with SAPIEN-3.

BACKGROUND: Baseline conduction abnormalities are known risk factors for permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR). We sought to determine the impact of baseline right bundle branch block (RBBB), left bundle branch block (LBBB), left anterior hemiblock (LAHB), first-degree atrioventricular block (AVB) and atrial fibrillation/flutter (AF) on TAVR outcomes. METHODS: Consecutive patients who underwent transfemoral TAVR with SAPIEN-3 (S3) were included. We excluded patients with prior PPM, nontransfemoral access or valve-in-valve. RESULTS: Among 886 patients, baseline RBBB was seen in 15.9%, LBBB in 6.3%, LAHB in 6.2%, first-degree AVB in 26.3% and AF in 37.5%. The rate of 30-day PPM was 10.1%. Baseline RBBB (OR 4.005; 95% CI 2.386-6.723; p < .001) and first-degree AVB (OR 1.847; 95% CI 1.133-3.009; p = .014) were independent predictors of 30 day PPM. LAHB also resulted in higher PPM rates but only in unadjusted analysis (21.8% vs. 9.4%; p = .003). Baseline LBBB and AF were associated with lower left ventricular ejection fraction (LVEF) at both baseline and 1 year after TAVR. However, Δ LVEF over time were noted to be similar with baseline LBBB (1.8% vs. 1.4%; p = .809) and AF (1.1% vs. 1.7%; p = .458). Moreover, baseline AF was also associated with higher stroke/transient ischemic attack (TIA) at 1 year (4.4% vs. 1.8%; p = .019), 1-year major adverse cardiac and cerebrovascular events (MACCE) (19.5% vs. 13.3%; p = .012) and 2 year mortality (23.5% vs. 15.2%; p = .016). None of the other baseline conduction defects affected long-term mortality or MACCE. CONCLUSION: In our S3 TAVR population, baseline RBBB and first-degree AVB predicted higher PPM risk. Prior LBBB and AF were associated with lower LVEF at both baseline and 1 year. Lastly, preexisting AF was associated with higher rates of mortality, stroke/TIA, and MACCE.