Combined telemonitoring and telecoaching for heart failure improves outcome.

Telemedicine has been shown to improve the outcome of heart failure (HF) patients in addition to medical and device therapy. We investigate the effectiveness of a comprehensive telehealth programme in patients with recent hospitalisation for HF on subsequent HF hospitalisations and mortality compared to usual care in a real-world setting. The telehealth programme consists of daily remote telemonitoring of HF signs/symptoms and regular individualised telecoaching sessions. Between January 2018 and September 2020, 119,715 patients of a German health insurer were hospitalised for HF and were eligible for participation in the programme. Finally, 6065 HF patients at high risk for re-hospitalisation were enroled. Participants were retrospectively compared to a propensity score matched usual care group (n = 6065). Median follow-up was 442 days (IQR 309-681). Data from the health insurer was used to evaluate outcomes. After one year, the number of hospitalisations for HF (17.9 vs. 21.8 per 100 patient years, p < 0.001), all-cause hospitalisations (129.0 vs. 133.2 per 100 patient years, p = 0.015), and the respective days spent in hospital (2.0 vs. 2.6 days per year, p < 0.001, and 12.0 vs. 13.4, p < 0.001, respectively) were significantly lower in the telehealth than in the usual care group. Moreover, participation in the telehealth programme was related to a significant reduction in all-cause mortality compared to usual care (5.8 vs. 11.0 %, p < 0.001). In a real-life setting of ambulatory HF patients at high risk for re-hospitalisation, participation in a comprehensive telehealth programme was related to a reduction of HF hospitalisations and all-cause mortality compared to usual care.

Incidence and Predictors of Ventricular Arrhythmias in Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is characterized by heart failure, conduction abnormalities and arrhythmias. The incidence of ventricular arrhythmias, particularly ventricular tachycardias (VTs), in wtATTR-CM is unclear. With the development of targeted therapies and improved overall prognosis, there is an unmet need to identify patients at high risk for VTs who might benefit from ICD therapy. METHODS: Between 2017 and 2022, 72 patients diagnosed with wtATTR-CM were prospectively evaluated for the presence of ventricular arrhythmias using a Holter ECG. VTs were defined as >3 consecutive beats with a heart rate > 100 beats per minute originating from a ventricle. RESULTS: The incidence of VTs was 44% (n = 32/72) in unselected wtATTR-CM patients. Patients with VT showed significantly more severe left ventricular (LV) hypertrophy (septum diameter 21 ± 2.6 vs. 19 ± 3.0 mm, p = 0.006), reduced LV ejection fraction (47 ± 8 vs. 52 ± 8%, p = 0.014) and larger left atria (32 ± 7 vs. 28 ± 6 mm2, p = 0.020), but no differences in cardiac markers such as NTproBNP and troponin. In a multivariable model, LV hypertrophy (LV mass indexed, OR = 1.02 [1.00-1.03], p = 0.031), LV end-diastolic diameter (OR = 0.85 [0.74-0.98], p = 0.021) and LV end-systolic diameter (OR = 1.19 [1.03-1.349], p = 0.092) were predictive for VT occurrence with an area under the receiver operating characteristic of 0.76 [0.65-0.87]. CONCLUSIONS: The incidence of ventricular arrhythmia in wtATTR-CM is high and is associated with an advanced stage of left ventricular disease. Further studies are needed evaluating the role of VTs in predicting sudden cardiac death and the benefit of ICD therapy in wtATTR-CM.

Echocardiographic evaluation of left ventricular function using an automated analysis algorithm is feasible for beginners and experts: comparison with invasive and non-invasive methods.

AIMS: Echocardiographic measurement of left ventricular function using a user-friendly automated three-dimensional algorithm is highly attractive as it promises quick and accurate diagnosis, circumventing limitations associated with visual estimation or manual biplane measurements. We sought to assess the feasibility and correlation of such automated analysis with clinically established methods. METHODS: A total of 198 patients undergoing transthoracic echocardiography (TTE) with assessment of left ventricular parameters by automated software algorithm (Philips 3D-Heartmodel; 3D-HM) which additionally had either left ventricular angiography (LVA) or cardiac magnetic resonance (CMR) within 24 h of the TTE examination were analyzed. Left ventricular parameters (left ventricular end-diastolic volume, LVEDV, left ventricular end-systolic volume, LVESV as well as left ventricular ejection fraction, LVEF) were compared between 3D-HM, CMR and LVA. RESULTS: Correlation of left ventricular measurements was overall good to excellent and stronger for CMR (EF r = 0.824) than for LVA (EF r = 0.746). Unexperienced and expert clinicians yielded comparable good results. For CMR, highest correlation was detected in patients with BMI < 25 and excellent image quality. High agreement was seen between 3D-HM and CMR or LVA when stratifying patients according to heart failure categories. CONCLUSIONS: Echocardiographic quantification of left ventricular parameters using a software-based algorithm correlated well with established invasive and non-invasive modalities in the clinical setting, even for unexperienced clinicians. Such automated approaches are promising as they allow a reliable, more observer-independent as well as reproducible assessment of left ventricular function.

Impact of Tele-Coaching During the COVID-19 Pandemic on Risk-Reduction Behavior of Patients with Heart Failure.

Introduction: Our study assessed the effectiveness of tele-coaching over written information in educating patients with chronic heart failure (CHF) at high risk of hospitalization about corona virus disease 2019 (COVID-19). We analyzed the impact on number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and self-reported behavior change. Methods: In April 2020, a tele-coaching module and written summary about COVID-19, risk-reduction measures for prevention of COVID-19, and appropriate consultation of medical attention during the pandemic were integrated into an established tele-coaching program. Three hundred seventy-eight patients who had received both tele-coaching and written information 3 weeks earlier were interviewed using a structured questionnaire and compared with 1,748 patients who had only received written information at this point. Results: Tele-coaching had no short-term effect on numbers of SARS-CoV-2 infections. However, patients receiving tele-coaching reported significantly more behavioral changes, including increased room ventilation (88% vs. 78%, p < 0.0001), surface cleaning (80% vs. 70%, p = 0.0006), wearing of face masks (59% vs. 51%, p = 0.013), and reduced usage of public transport (77% vs. 68%, p = 0.0003), despite no observed difference in recall about risk-reduction measures. Moreover, tele-coaching improved patients' knowledge about how to seek medical help in an emergency (46% vs. 36%, p = 0.0006), with a significant reduction in self-reported doctors' appointments (304 vs. 413 per 1,000 patients, p = 0.002) and hospital visits (50 vs. 87 per 1,000, p = 0.033) during the first peak of the pandemic. Conclusion: In a population of patients with CHF at high risk of hospitalization, COVID-19-specific tele-coaching effectively supported behavioral changes and significantly reduced face-to-face medical contacts in a short-term follow-up period.

Systematic assessment of health care perception in adults with congenital heart disease in Germany.

BACKGROUND: The number of adults with congenital heart disease (ACHD) is steadily rising due to increased survival rate and improved medical resources. Accordingly, more than 330,000 ACHD are currently living in Germany. Almost all of them require lifelong specialized medical follow-up for their chronic heart disease, often accompanied by residua, sequelae, or comorbidities. Primary care physicians (PCPs) are a crucial factor in directing patients to ACHD specialists or specialized institutions, but despite all efforts, the number of ACHD under specialized care is low, the lost-to-follow-up rate is high, and the morbidity and mortality is substantial. The present cross-sectional study was designed to systematically characterize the health care of ACHD from a patient perspective, including (I) use of medical care by ACHD, (II) medical counselling needs, and (III) perceived satisfaction with health care. METHODS: The German-wide analysis was based on a 25-item questionnaire designed to address different aspects of medical status and health issues of ACHD from their own perspective, performed between May of 2017 and July of 2020. RESULTS: A total of 4,008 ACHD (52% female; mean age 41.9±17.2 years) completed the questionnaire. The majority of ACHD (3,524, 87.9%) reported, that they consulted their PCP for non-cardiac health problems, and 49.7% (n=1,991) consulted their PCP also for medical problems associated with the underlying CHD. Almost all ACHD reported a need for medical advice concerning exercise capacity and daily life activities, occupational skills, pregnancy, rehabilitation, genetic counselling, insurance, and retirement. A total of 1,840 (45.9%) patients were not aware of the existence of certified ACHD specialists or centers. Moreover, 2,552 (67.6%) of those surveyed were uninformed about patient organizations for ACHD. CONCLUSIONS: The present study demonstrates that ACHD are largely uninformed about the ACHD care structures available nationwide, although the patients have a great need for specialized follow-up, advice, and care.

Role of the Ambulatory Assessed Apnea-Hypopnea Index for Predicting Recurring Atrial Fibrillation After Ablation Therapy.

Catheter ablation is an effective treatment for atrial fibrillation (AF). Obstructive sleep apnea (OSA) is a known risk factor for recurrent AF. The apnea-hypopnea index (AHI) is a measurement tool to screen patients for OSA. We sought to evaluate if the ambulatory assessed AHI is associated with AF recurrence following AF catheter ablation. 187 patients with paroxysmal (n = 155) or early persistent (n = 32) AF presenting for catheter ablation were included in the study. AHI was determined prior to ablation using an ambulatory screening device. All patients underwent pulmonary vein isolation (PVI). In patients with early persistent AF (17%) additional ablation of complex fractionated atrial electrograms (CFAE) was performed. Clinical follow-up was available after 3 and 12 months including 7-day Holter-ECG. All 187 patients (60.3 ± 11.4 years, 64.2% male) completed the 3 months follow-up and 170 patients the 12 months follow-up. A pathological AHI ≥15 was found in 45/187 (24.1%) patients. Additional CFAE did not differ between patients with an AHI ≥15 and AHI <15 (p = 0.663). After 3 months, 12/41 (29.3%) patients with AHI ≥15 showed recurrent AF compared to 24/146 (16.4%) patients with AHI <15 (p = 0.066). After 12 months, AHI ≥15 was associated with a significant higher rate of AF recurrence of 47.4% (18/38) versus 26.5% (35/132) in patients with AHI <15 (p = 0.014). In the logistic regression analysis AHI ≥15 was an independent predictor of recurrent AF at 12 months (p = 0.011). In conclusion, ambulatory assessed AHI ≥15 is associated with increased risk for AF recurrence following catheter ablation. OSA screening should be performed in AF patients as it might influence catheter ablation success.

The Genetic Makeup of the Electrocardiogram.

The electrocardiogram (ECG) is one of the most useful non-invasive diagnostic tests for a wide array of cardiac disorders. Traditional approaches to analyzing ECGs focus on individual segments. Here, we performed comprehensive deep phenotyping of 77,190 ECGs in the UK Biobank across the complete cycle of cardiac conduction, resulting in 500 spatial-temporal datapoints, across 10 million genetic variants. In addition to characterizing polygenic risk scores for the traditional ECG segments, we identified over 300 genetic loci that are statistically associated with the high-dimensional representation of the ECG. We established the genetic ECG signature for dilated cardiomyopathy, associated the BAG3, HSPB7/CLCNKA, PRKCA, TMEM43, and OBSCN loci with disease risk and confirmed this association in an independent cohort. In total, our work demonstrates that a high-dimensional analysis of the entire ECG provides unique opportunities for studying cardiac biology and disease and furthering drug development. A record of this paper's transparent peer review process is included in the Supplemental Information.

Facts about the General Medical Care of Adults with Congenital Heart Defects: Experience of a Tertiary Care Center.

Background: Due to the increase in survival rates for congenital heart disease (CHD) in the last decades, over 90% of patients today reach adulthood. Currently, there are more than 300,000 adults with CHD (ACHD) living in Germany. They have an increased need for specialized medical care, since almost all ACHD have chronic heart disease and suffer from specific chronic symptoms, risks, and sequelae. Primary care physicians (PCPs) play a crucial role in referring patients to ACHD specialists or specialized institutions. This cross-sectional study is intended to clarify the real-world care of ACHD from the PCP's perspective. Methods: This analysis, initiated by the German Heart Centre Munich, was based on a 27-item questionnaire on actual ACHD health care practice in Germany from the PCP's perspective. Results: In total, 767 questionnaires were considered valid for inclusion. The majority of the PCPs were general practitioners (95.9%), and 84.1% had cared for ACHD during the past year. A majority (69.2%) of the PCPs had cared for patients with simple CHD, while 50.6% and 33.4% had cared for patients with moderate and severe CHD, respectively, in all age groups. PCPs treated almost all typical residual symptoms and sequelae, and advised patients regarding difficult questions, including exercise capacity, pregnancy, genetics, and insurance matters. However, 33.8% of the PCPs did not even know about the existence of certified ACHD specialists or centers. Only 23.9% involved an ACHD-specialized physician in their treatment. In cases of severe cardiac issues, 70.8% of the PCPs referred patients to ACHD-certified centers. Although 52.5% of the PCPs were not sufficiently informed about existing structures, 64.2% rated the current care situation as either "very good" or "good". Only 26.3% (n = 190) of the responding physicians were aware of patient organizations for ACHD. Conclusions: The present study showed that the majority of PCPs are not informed about the ACHD care structures available in Germany. The need for specialized ACHD follow-up care is largely underestimated, with an urgent need for optimization to reduce morbidity and mortality. For the future, solutions must be developed to integrate PCPs more intensively into the ACHD care network.

[Meaningful diagnostics: genetics]. / Sinnvolle Diagnostik: Genetik.

Molecular genetic analysis is an important component in the diagnostics of some cardiovascular diseases; however, genetic testing should not be used as a screening technique as the diagnostic value strongly depends on anamnestic and clinical factors, such as a positive family history and the disease phenotype. In cardiovascular diseases with high mutation detection rates, e.g. hypertrophic cardiomyopathy and primary arrhythmia syndromes (long QT syndrome, catecholaminergic polymorphic ventricular tachycardia) genetic testing should be included in the diagnostic work-up. Family screening of first-degree relatives (cascade screening) is a particularly important application of genetic diagnostics for a timely identification of asymptomatic mutation carriers and initiation of preventive treatment. A molecular autopsy, also known as postmortem molecular genetic DNA testing, is a special indication for genetic diagnostics. It is particularly useful in the analysis of sudden cardiac death victims for the identification of disease-specific gene mutations. Therefore, given a selective use and a thorough evaluation of the test results, molecular genetic analyses can make a meaningful diagnostic and prognostic contribution. Potential applications of genetic analyses in the future are polygenic cardiovascular diseases. The use of new high-throughput technologies enables the analysis of multiple genetic variants, which can then be included in the calculation of a polygenic risk score for the prediction of the probability of a specific disease.

Left ventricular geometry and function in early repolarization: results from the population-based Gutenberg Health Study.

AIMS: The electrocardiographic pattern of early repolarization (ER) is related to increased cardiac mortality in the general population. The pathophysiological basis of ER is largely unknown. We investigated the association of echocardiographic structural and functional parameters of the left ventricle with the presence of ER in the community. METHODS AND RESULTS: The presence of ER (ER+) was assessed in 13,878 participants (mean age 54.6 years, 51.1% women) of the Gutenberg Health Study and related to left ventricular structure and function derived from standard echocardiography. The prevalence of ER was 5.0% (694/13,878), with higher prevalence in men than women (6.6% vs. 3.5%, p < 0.001). In men baseline characteristics differed including a lower BMI and a lower heart rate in ER+ individuals, whereas in women there were only minor differences. Multivariable-adjusted logistic regression analysis in men showed an association of ER with smaller diameters (left-ventricular end-diastolic diameter: OR 0.77 95% CI 0.69-0.86, p < 0.001; left-ventricular end-systolic diameter: OR 0.86 95% CI 0.78-0.95, p = 0.0035), and lower left-ventricular end-diastolic and end-systolic volume (OR 0.72 95% CI 0.65, 0.80, p < 0.001 and OR 0.80 95% CI 0.72, 0.89, p < 0.001). In women, the associations of ER with left ventricular diameters and volumes showed a similar direction, but were not as pronounced. CONCLUSION: In the community, the ER pattern predominantly occurs in men with a low heart rate and a slender habit. Furthermore, ER is not associated with higher left ventricular mass or size but rather with smaller left ventricular diameters and volumes with a regular systolic and diastolic function. Patterns were comparable in women, but less strong.

Prophylactic ECMO during TAVI in patients with depressed left ventricular ejection fraction.

BACKGROUND: This study investigated the impact of prophylactic veno-arterial extracorporeal membrane oxygenation (pECMO) in patients with depressed left ventricular ejection fraction (dLVEF) undergoing transcatheter aortic valve implantation (TAVI). METHODS: Out of 1490 patients undergoing TAVI at two centers (2010-2015), 222 patients had dLVEF (≤ 40%). Of these, 21 patients (10%) underwent TAVI with pECMO. Complications and outcome according to pECMO were analyzed in the entire and in a propensity-matched population. RESULTS: In the entire population, patients with pECMO had a higher logEuroScore I (33% ± 19 vs. 25% ± 17; p = 0.037), worse LVEF (26% ± 7 vs. 32% ± 7; p = 0.001), more major bleedings (29% vs. 9%; p = 0.015), higher transfusion rate (30% vs. 10%; p = 0.019) and longer in-hospital stay (9.0 [7.0;14.0] vs. 7.0 [5.0;10.0] days; p = 0.024). After propensity matching only transfusion rate remained higher with pECMO (30% vs. 7%; p = 0.025). In the entire population, rate and risk of 30-day mortality was higher with pECMO (24% vs. 6%, HR 95%CI 4.29 [1.51-12.19]; p = 0.006). In the matched population, this effect was attenuated (24% vs. 12%, HR 95%CI 2.09 [0.61-7.23]; p = 0.243). Cumulative rate and risk of 1-year mortality did not differ in the entire (log-rank p = 0.069; 39% vs. 22%, HR 95%CI 1.99 [0.94-4.24]; p = 0.074) nor in the matched population (log-rank p = 0.520; 39% vs. 31%, HR 95%CI 1.34 [0.55-3.28]; p = 0.523). CONCLUSION: In patients with dLVEF undergoing TAVI, periprocedural pECMO support does not seem to improve patient outcome.

The early repolarization pattern: Echocardiographic characteristics in elite athletes.

BACKGROUND: The electrocardiographic early repolarization (ER) pattern is associated with idiopathic ventricular fibrillation and increased long-term cardiovascular mortality. Whether structural cardiac aberrations influence the phenotype is unclear. Since ER is particularly common in athletes, we evaluated its prevalence and investigated predisposing echocardiographic characteristics and cardiopulmonary exercise capacity in a cohort of elite athletes. METHODS: A total of 623 elite athletes (age 21 ± 5 years) were examined during annual preparticipation screening from 2006 until 2012 including electrocardiography, echocardiography, and exercise testing. ECGs were analyzed with focus on ER. All athletes participated in a clinical follow-up. RESULTS: The prevalence of ER was 17% (108/623). ER-positive athletes were predominantly male (71%, 77/108), showed a lower heart rate (57.1 ± 9.3 bpm versus 60.0 ± 11.2 bpm; p = 0.015) and a higher lean body mass compared to ER-negative participants (88.1% ± 5.6% versus 86.5% ± 6.3%; p = 0.015). Echocardiographic measurements and cardiopulmonary exercise capacity in male and female athletes with and without ER largely showed similar results. Only the notching ER subtype (n = 15) was associated with an increased left atrial diameter (OR 7.01, 95%CI 1.65-29.83; p = 0.008), a higher left ventricular mass (OR 1.02, 95%CI 1.00-1.03; p = 0.038) and larger relative heart volume (OR 1.01, 95%CI 1.00-1.01; p = 0.01). During a follow-up of 7.4 ± 1.5 years, no severe cardiovascular event occurred in the study sample. CONCLUSIONS: In elite athletes presence of ER is not associated with distinct alterations in echocardiography and cardiopulmonary exercise. Athletes presenting with ER are rather male, lean with a low heart rate.

The narrow-sense and common single nucleotide polymorphism heritability of early repolarization.

BACKGROUND: Early repolarization (ER) is a risk marker for sudden cardiac death. Higher risk is associated with horizontal/descending ST-segment ER in the inferior or inferolateral ECG leads. Studies in family cohorts have demonstrated substantial heritability for the ER pattern, but genome-wide association studies (GWAS) have failed to identify statistically significant and replicable genetic signals. METHODS AND RESULTS: We assessed the narrow-sense and common single nucleotide polymorphism (SNP) heritability of ER and ER subtypes using ECG data from 5829 individuals (TwinsUK, BRIGHT and GRAPHIC cohorts). ER prevalence was 8.3%. In 455 monozygous vs 808 dizygous twin pairs, concordances and twin correlations for ER subtypes (except horizontal/descending ST-segment ER) were higher and familial resemblance (except notched ER) was significant. Narrow-sense heritability estimates derived from 1263 female twin pairs using the structural equation program Mx ranged from 0.00-0.47 and common SNP heritability estimates derived from 4009 unrelated individuals of both sexes using Genome-wide Restricted Maximum Likelihood (GREML) ranged from 0.00-0.36, but none were statistically significant. CONCLUSION: From our data, ER shows limited genetic predisposition. There appears to be significant environmental influence and these modest narrow-sense and common SNP heritability estimates may explain why previous GWAS have been unsuccessful.

Lipid-modifying therapy and low-density lipoprotein cholesterol goal attainment in patients with familial hypercholesterolemia in Germany: The CaReHigh Registry.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is amongst the most common genetic disorders encountered in primary care. Yet, only a minority of affected patients is diagnosed and treated. This interim analysis of the CaRe High Registry aims at examining the state of treatment and attainment of lipid goals in German FH patients. METHODS: The CaRe High registry includes FH patients from lipid clinics and private practices. Data have been collected using questionnaires filled in by the recruiting physicians and by interviewing the participating patients. RESULTS: We examined 512 F H patients diagnosed according to clinical criteria. Median age at the time of the first FH diagnosis was 39 (25th and 75th percentile: 27-50) years, median treatment naïve LDL cholesterol (LDL-C) was 239.4 mg/dl (6.19 mmol/l), 25th to 75th percentile 191.8-342.5 mg/dl (4.96-8.86 mmol/l). 27% of the participants did not receive lipid-lowering drugs. Among the patients treated with lipid-lowering drugs, 19% received a PCSK9 inhibitor (PCSK9i) in combination with a statin, 9% were treated with a PCSK9i alone and 3% were treated with a combination of PCSK9i and a non-statin drug. Patients with pre-existing CVD were more likely to be treated with lipid-lowering drugs and more likely to receive a PCSK9i, but LDL-C targets were only achieved by a minority of patients (<20%). Gap to target LDL-C was lowest and the median achieved LDL-C reduction was 1.4 times higher with PCSK9i treatment than with (oral) lipid-lowering therapy without PCSK9i. CONCLUSIONS: The Care High registry has included patients with the typical clinical features of familial hypercholesterolemia. PCSK9i treatment in addition to standard therapy allows attainment of target values in many patients with initially very high LDL-C.

Determinants of elevated carbohydrate antigen 125 in patients with severe symptomatic aortic valve stenosis referred for transcatheter aortic valve implantation.

PURPOSE: Elevated carbohydrate antigen 125 (CA125) predicts adverse outcome after transcatheter aortic valve implantation (TAVI). While known underlying pathophysiological mechanisms of elevated CA125 include serosal effusions and inflammatory stimuli, clinical determinants associated with elevated CA125 in patients referred for TAVI remain unknown. Therefore, we investigated clinical, laboratory and echocardiographic determinants of elevated CA125 in patients with severe aortic valve stenosis referred for TAVI. METHODS: This study includes 650 patients with severe aortic stenosis referred for TAVI. Baseline CA125 was determined by an immunoassay and dichotomized (elevated versus normal) based on the manufacturer cutoff value (>35 U/mL). RESULTS: CA125 elevation was present in 28% (181/650). Patients with elevated CA125 had an overall worse clinical profile and were more symptomatic with a higher rate of NYHA class III/IV (80% versus 58%; p < 0.001). In a multivariate analysis, independent predictors of elevated CA125 were New York Heart Association (NYHA) class, baseline hemoglobin, C-reactive protein (CRP), left ventricular ejection fraction and severe tricuspid regurgitation. CONCLUSION: Elevated CA125 levels in patients referred for TAVI summarize a subset of patients with an overall worse clinical profile who are more symptomatic.

Emergency extracorporeal membrane oxygenation in transcatheter aortic valve implantation: A two-center experience of incidence, outcome and temporal trends from 2010 to 2015.

BACKGROUND: Although the incidence of periprocedural complications has decreased in transcatheter aortic valve implantation (TAVI), life-threatening complications occur and emergency veno-arterial extracorporeal membrane oxygenation (vaECMO) can provide immediate circulatory stabilization. We report our two-center experience of vaECMO during life-threatening complications in TAVI. METHODS: From January 2010 to December 2015, 1,810 consecutive patients underwent TAVI at two centers. Clinical characteristics, type of complication, outcome and temporal trends in the requirement of emergency vaECMO were evaluated. RESULTS: Life-threatening complications requiring vaECMO occurred in 1.8% of cases (33 patients; 22 transfemoral, 11 transapical). Indications for vaECMO were ventricular rupture (30%, 10/33), low output (15%, 5/33), bleeding (12%, 4/33), coronary artery impairment (9%, 3/33), ventricular arrhythmias (6%, 2/33), severe aortic regurgitation (6%, 2/33), aortic annular rupture (6%, 2/33), and aortic dissection (3%, 1/33). In 4 cases, no definite cause for hemodynamic instability was identified. Conversion to open heart surgery was necessary in 42% of patients (14/33). Percutaneous coronary intervention was performed in all cases with coronary artery impairment (9%, 3/33). Patients with severe aortic regurgitation (6%, 2/33) underwent emergency valve-in-valve implantation. Other patients received, in addition to vaECMO support conservative treatment (42%, 14/33). In-hospital mortality and 30-day mortality were 46% (15/33). Of patients discharged, 67% (12/18) had no neurological impairment, whereas mild and severe neurological impairment was found in 11% (2/18) and 22% (4/18), respectively. From 2010 to 2015, with increasing procedures (from n = 43 to n = 553) requirement of vaECMO decreased from 9.3% to 0.9% (P for the trend <0.001). CONCLUSION: Over a 6-year period, need for emergency vaECMO during TAVI significantly decreased over time. Despite high in-hospital mortality, vaECMO represents a feasible strategy for hemodynamic support in case of life-threatening complications.

Ventricular and Supraventricular Ectopy in Subjects With Early Repolarization.

Early repolarization (ER) is a common electrocardiographic (ECG) finding that is associated with an increased risk of idiopathic ventricular fibrillation and sudden cardiac death. This study investigated whether the presence of ER is a predictor of ventricular and supraventricular ectopy as a marker for electrical instability. Standard 12-lead electrocardiograms of the first follow-up in the population-based Study of Health in Pomerania (SHIP-1) (n = 3,300, age 20 to 79 years) were analyzed to identify subjects with an ER pattern. Ventricular and supraventricular ectopy was assessed via portable tele-ECG cards recording 2 electrocardiograms daily over the course of 4 weeks. Data of 1,630 subjects (n = 83,833 ECG card recordings, average 51.4 per subject) were analyzed for ventricular and supraventricular ectopy using a standardized automated algorithm. Associations of ER and several forms of arrhythmias were assessed using a 2-sided Fisher's exact test or t test, where appropriate. Overall, prevalence of ER in the SHIP-1 population was 4.8%. Presence of ER was not associated with the occurrence of ventricular and supraventricular arrhythmias (p ≥0.05 for all analyses). Furthermore, subgroup analyzes for ER localization (inferior) and ST-segment morphology (horizontal/descending) did not show any association with arrhythmic events. In conclusion, presence of the ER pattern is not associated with an increased occurrence of ventricular or supraventricular arrhythmias as assessed by serial ECG card recordings in this large population-based sample.

The Prevalence and Significance of the Early Repolarization Pattern in Sudden Arrhythmic Death Syndrome Families.

BACKGROUND: The early repolarization (ER) pattern is associated with sudden death and has been shown to be heritable. Its significance when identified in families affected by sudden arrhythmic death syndrome (SADS) remains unclear. METHODS AND RESULTS: We analyzed 12-lead ECGs of 401 first-degree relatives of individuals who had died from SADS. The prevalence of ER patterns was compared with family-clustered controls. ER was more common in SADS family members than in controls (21% versus 8%; odds ratio: 5.14; 95% confidence interval, 3.37-7.84) independent of the presence of a familial cardiac diagnosis. Both ascending and horizontal ER patterns were more common. In addition, ER was investigated for associations with findings from ajmaline provocation (n=332), exercise ECG (n=304), and signal-averaged ECG (n=118) when performed. ER was associated with a trend toward late depolarization, in general was suppressed with exercise and was unaffected by ajmaline. Inferior and horizontal patterns were, however, more likely to persist during exercise. Augmentation of ER with ajmaline was rare. CONCLUSIONS: The ER pattern is more common in SADS family members than controls adjusted in particular for relatedness. The increased prevalence is irrespective of ER subtype and the presence of other inherited arrhythmia syndromes. ER may therefore represent an underlying heritable arrhythmia syndrome or risk factor for sudden death in the context of other cardiac pathology. The differing response of ER subtypes to exercise and ajmaline provocation suggests underlying mechanisms of both abnormal repolarization and depolarization.

Novel frame-shift mutation in PKP2 associated with arrhythmogenic right ventricular cardiomyopathy: a case report.

BACKGROUND: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited disease mainly found in young people causing malignant arrhythmias which can result in sudden cardiac death. Due to unspecific symptoms the diagnosis of ARVC is still challenging and requires clinical testing and expert knowledge. Genetic testing of index patients is helpful in the primary diagnosis and further testing of family members may allow for prevention of sudden cardiac death. CASE PRESENTATION: We report a case of newly diagnosed ARVC where genetic testing identified a novel familial frame-shift mutation in the PKP2 gene. Screening of the family members identified both children and the father as mutation carriers following an autosomal-dominant inheritance pattern. CONCLUSION: Our findings emphasize the importance of genetic family screening after the identification of a causative mutation in an index case.

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as ß1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.