Morten Kvistholm Jensen

Long-Term Outcome of Percutaneous Transluminal Septal Myocardial Ablation in Hypertrophic Obstructive Cardiomyopathy A Scandinavian Multicenter Study

Background— Single-center reports on percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy have shown considerable differences in outcome. Methods and Results— We report the long-term outcome of 313 PTSMA procedures performed in 279 patients with hypertrophic obstructive cardiomyopathy aged 59±14 years from 1999 to 2010 in 4 Scandinavian centers. Sixty-nine percent of patients had ≥1 comorbidity at baseline. The median (interquartile range) of left ventricular outflow tract gradient at rest was reduced from 58 mm Hg (34 to 89 mm Hg) at baseline to 12 mm Hg (8 to 24 mm Hg) at 1-year (P<0.001) and during Valsalva maneuver from 93 mm Hg (70 to 140 mm Hg) to 21 mm Hg (11 to 42 mm Hg) (P<0.001). The proportion of patients with syncope was reduced from 18% to 2% (P<0.001), and the proportion in New York Heart Association class III/IV was reduced from 94% to 21% (P<0.001). All treatment effects remained stable during the follow-up. New York Heart Association class III/IV at the most recent follow-up (2.9±2.6 years) was associated with diabetes mellitus (P=0.03), chronic obstructive pulmonary disease (P=0.02), and valve disease unrelated to hypertrophic cardiomyopathy (P<0.01). In-hospital mortality was 0.3%. The 1-, 5- and 10-year survival rates were 97%, 87%, and 67%, respectively (P=0.06 versus an age- and sex-matched background population) in all patients and 99%, 94%, and 88%, respectively (P=0.12) in patients aged <60 years (48±9 years, n=141). Age (hazard ratio, 1.07; 95% CI, 1.03 to 1.1) was the only predictor of survival. Conclusions— In this multicenter study, the in-hospital mortality after PTSMA was low despite considerable comorbidities. The hemodynamic and symptomatic effects were sustained long term. The long-term symptomatic outcome was associated with baseline comorbidities. The 10-year survival rate was comparable to that in an age- and sex-matched background population, and age was the only predictor of survival.

Alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy: low incidence of sudden cardiac death and reduced risk profile

Background The infarction induced by alcohol septal ablation (ASA) may predispose to arrhythmia and sudden cardiac death (SCD). Objective To assess survival, incidence of SCD after ASA and effects of ASA on the traditional risk factors (RFs) for SCD. Design An observational cohort-study (follow-up 8.4±4 years). Setting A dual-centre cohort. Patients 470 consecutive patients (age 56±14 years) with obstructive hypertrophic cardiomyopathy (HCM) (1996–2010). Interventions Clinically applied echo-contrast-guided ASA treatments. Main outcome measures All-cause mortality, SCD and RFs for SCD before and after ASA. Results The 10-year survival was 88% (annual all-cause death rate 1.2%) after ASA compared with 84% (p=0.06) in a matched background population. The 10-year survival free of SCD was 95% (annual SCD rate 0.5%). ASA reduced the prevalence of abnormal blood pressure response (from 23% to 9%, p<0.001), syncope (26% to 2%, p<0.001), non-sustained ventricular tachycardia (NSVT) (23% to 17%, p<0.05) and maximal wall thickness ≥30 mm (7% to 2%, p<0.001). There was a family history of SCD in 19% of the patients. The proportion of patients at high risk—that is, two or more RFs (n=89), was reduced from 25% to 8% (p<0.001). A RF score ≥2 before ASA was not associated with SCD (n=361, p=0.31). Conclusions Survival in ASA-treated patients was similar to that in the background population. The number of RFs, including the prevalence of NSVT, was markedly reduced by ASA and the incidence of SCD was correspondingly low. Thus, clinically applied ASA was safe.

Long-Term Outcome of Percutaneous Transluminal Septal Myocardial Ablation in Hypertrophic Obstructive Cardiomyopathy

Background— Single-center reports on percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy have shown considerable differences in outcome. Methods and Results— We report the long-term outcome of 313 PTSMA procedures performed in 279 patients with hypertrophic obstructive cardiomyopathy aged 59±14 years from 1999 to 2010 in 4 Scandinavian centers. Sixty-nine percent of patients had ≥1 comorbidity at baseline. The median (interquartile range) of left ventricular outflow tract gradient at rest was reduced from 58 mm Hg (34 to 89 mm Hg) at baseline to 12 mm Hg (8 to 24 mm Hg) at 1-year (P<0.001) and during Valsalva maneuver from 93 mm Hg (70 to 140 mm Hg) to 21 mm Hg (11 to 42 mm Hg) (P<0.001). The proportion of patients with syncope was reduced from 18% to 2% (P<0.001), and the proportion in New York Heart Association class III/IV was reduced from 94% to 21% (P<0.001). All treatment effects remained stable during the follow-up. New York Heart Association class III/IV at the most recent follow-up (2.9±2.6 years) was associated with diabetes mellitus (P=0.03), chronic obstructive pulmonary disease (P=0.02), and valve disease unrelated to hypertrophic cardiomyopathy (P<0.01). In-hospital mortality was 0.3%. The 1-, 5- and 10-year survival rates were 97%, 87%, and 67%, respectively (P=0.06 versus an age- and sex-matched background population) in all patients and 99%, 94%, and 88%, respectively (P=0.12) in patients aged <60 years (48±9 years, n=141). Age (hazard ratio, 1.07; 95% CI, 1.03 to 1.1) was the only predictor of survival. Conclusions— In this multicenter study, the in-hospital mortality after PTSMA was low despite considerable comorbidities. The hemodynamic and symptomatic effects were sustained long term. The long-term symptomatic outcome was associated with baseline comorbidities. The 10-year survival rate was comparable to that in an age- and sex-matched background population, and age was the only predictor of survival.

Penetrance of hypertrophic cardiomyopathy in children and adolescents: a 12-year follow-up study of clinical screening and predictive genetic testing.

Background— The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has been only sparsely described. We studied the penetrance of HCM and the short- and long-term outcomes of clinical screening and predictive genetic testing of child relatives of patients with HCM. Methods and Results— Ninety probands and 361 relatives were included in a family screening program for HCM (1994–2001). Eleven sarcomere genes, CRYAB, &agr;-GAL, and titin were screened. Sixty-six relatives and 4 probands were <18 years of age at inclusion. Twelve child relatives were mutation carriers (age, 12 ± 5 years), and 26 had unknown genetic status, ie, relatives from families without identified mutations (n = 21) or not tested (n = 5) (age, 11 ± 5 years). Twenty-eight noncarriers (42%; age, 10 ± 4 years) served as control subjects. Two of 38 child relatives (5%) at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12 ± 1 years of follow-up, 2 of the 36 (6%; 95% confidence interval, 2–18) at-risk child relatives who were phenotype negative at inclusion had developed the HCM phenotype at 26 and 28 years of age. During follow-up, none of the child relatives experienced serious cardiac events. Participation in the screening program had no long-term negative psychological impact. Conclusions— The penetrance of HCM in phenotype-negative child relatives at risk of developing HCM was 6% after 12 years of follow-up. The finding of phenotype conversion in the mid-20s warrants continued screening into adulthood. Forty-two percent of the child relatives were noncarriers, and repeat clinical follow-up could be safely limited to the remaining children.Background— The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has been only sparsely described. We studied the penetrance of HCM and the short- and long-term outcomes of clinical screening and predictive genetic testing of child relatives of patients with HCM. Methods and Results— Ninety probands and 361 relatives were included in a family screening program for HCM (1994–2001). Eleven sarcomere genes, CRYAB, α-GAL, and titin were screened. Sixty-six relatives and 4 probands were <18 years of age at inclusion. Twelve child relatives were mutation carriers (age, 12 ± 5 years), and 26 had unknown genetic status, ie, relatives from families without identified mutations (n = 21) or not tested (n = 5) (age, 11 ± 5 years). Twenty-eight noncarriers (42%; age, 10 ± 4 years) served as control subjects. Two of 38 child relatives (5%) at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12 ± 1 years of follow-up, 2 of the 36 (6%; 95% confidence interval, 2–18) at-risk child relatives who were phenotype negative at inclusion had developed the HCM phenotype at 26 and 28 years of age. During follow-up, none of the child relatives experienced serious cardiac events. Participation in the screening program had no long-term negative psychological impact. Conclusions— The penetrance of HCM in phenotype-negative child relatives at risk of developing HCM was 6% after 12 years of follow-up. The finding of phenotype conversion in the mid-20s warrants continued screening into adulthood. Forty-two percent of the child relatives were noncarriers, and repeat clinical follow-up could be safely limited to the remaining children. # Clinical Perspective {#article-title-34}

Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: results from the Euro-ASA registry

AIMS The first cases of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) were published two decades ago. Although the outcomes of single-centre and national ASA registries have been published, the long-term survival and clinical outcome of the procedure are still debated. METHODS AND RESULTS We report long-term outcomes from the as yet largest multinational ASA registry (the Euro-ASA registry). A total of 1275 (58 ± 14 years, median follow-up 5.7 years) highly symptomatic patients treated with ASA were included. The 30-day post-ASA mortality was 1%. Overall, 171 (13%) patients died during follow-up, corresponding to a post-ASA all-cause mortality rate of 2.42 deaths per 100 patient-years. Survival rates at 1, 5, and 10 years after ASA were 98% (95% CI 96-98%), 89% (95% CI 87-91%), and 77% (95% CI 73-80%), respectively. In multivariable analysis, independent predictors of all-cause mortality were age at ASA (P < 0.01), septum thickness before ASA (P < 0.01), NYHA class before ASA (P = 0.047), and the left ventricular (LV) outflow tract gradient at the last clinical check-up (P = 0.048). Alcohol septal ablation reduced the LV outflow tract gradient from 67 ± 36 to 16 ± 21 mmHg (P < 0.01) and NYHA class from 2.9 ± 0.5 to 1.6 ± 0.7 (P < 0.01). At the last check-up, 89% of patients reported dyspnoea of NYHA class ≤2, which was independently associated with LV outflow tract gradient (P < 0.01). CONCLUSIONS The Euro-ASA registry demonstrated low peri-procedural and long-term mortality after ASA. This intervention provided durable relief of symptoms and a reduction of LV outflow tract obstruction in selected and highly symptomatic patients with obstructive HCM. As the post-procedural obstruction seems to be associated with both worse functional status and prognosis, optimal therapy should be focused on the elimination of LV outflow tract gradient.

Mitochondrial Haplogroups Modify the Risk of Developing Hypertrophic Cardiomyopathy in a Danish Population

Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes coding for proteins involved in sarcomere function. The disease is associated with mitochondrial dysfunction. Evolutionarily developed variation in mitochondrial DNA (mtDNA), defining mtDNA haplogroups and haplogroup clusters, is associated with functional differences in mitochondrial function and susceptibility to various diseases, including ischemic cardiomyopathy. We hypothesized that mtDNA haplogroups, in particular H, J and K, might modify disease susceptibility to HCM. Mitochondrial DNA, isolated from blood, was sequenced and haplogroups identified in 91 probands with HCM. The association with HCM was ascertained using two Danish control populations. Haplogroup H was more prevalent in HCM patients, 60% versus 46% (p = 0.006) and 41% (p = 0.003), in the two control populations. Haplogroup J was less prevalent, 3% vs. 12.4% (p = 0.017) and 9.1%, (p = 0.06). Likewise, the UK haplogroup cluster was less prevalent in HCM, 11% vs. 22.1% (p = 0.02) and 22.8% (p = 0.04). These results indicate that haplogroup H constitutes a susceptibility factor and that haplogroup J and haplogroup cluster UK are protective factors in the development of HCM. Thus, constitutive differences in mitochondrial function may influence the occurrence and clinical presentation of HCM. This could explain some of the phenotypic variability in HCM. The fact that haplogroup H and J are also modifying factors in ischemic cardiomyopathy suggests that mtDNA haplotypes may be of significance in determining whether a physiological hypertrophy develops into myopathy. mtDNA haplotypes may have the potential of becoming significant biomarkers in cardiomyopathy.

Survival and sudden cardiac death after septal ablation for hypertrophic obstructive cardiomyopathy.

Abstract Objectives. Reports of long-term survival and the risk of sudden cardiac death (SCD) after percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) are sparse. Design. Survival and SCD in 77 PTSMA-treated patients (follow-up 3.5 ± 2.8 years) were analyzed. The future risk of SCD was assessed by risk stratification for SCD in 57 PTSMA patients at long-term follow-up (3.8 ± 2.8 years). Results. The five years survival of the PTSMA cohort (age 61 ± 12 years) was 83% compared to 79% in a control cohort (n = 90) of patients (age 52 ± 17 years) with hypertrophic cardiomyopathy (HCM) (Log Rank p = 0.8), and 91% (p = 0.01) in the background population. Five-year survival free of SCD was 94% after PTSMA compared to 99% (p = 0.13) in the HCM control cohort. Eight percent of patients had two or more risk factors for SCD at follow-up. Conclusion. The survival in the PTSMA-treated patients and in the HCM control cohorts was similar. The incidence of SCD and the future risk of SCD assessed by risk factors were not increased in the PTSMA cohort compared to the HCM control cohort. The excess mortality in the PTSMA cohort compared to the background population seems to be related to HCM rather than PTSMA.

Long-term survival and causes of death in patients with ST-elevation acute coronary syndrome without obstructive coronary artery disease

Aims We aimed to study survival and causes of death in patients with ST-elevation acute coronary syndrome (STE-ACS) with and without obstructive coronary artery disease (CAD). Methods and results We included 4793 consecutive patients with STE-ACS triaged for acute coronary angiography at a large cardiac invasive centre (2009-2014). Of these, 88% had obstructive CAD (stenosis ≥50%), 6% had non-obstructive CAD (stenosis 1-49%), and 5% had normal coronary arteries. Patients without obstructive CAD were younger and more often female with fewer cardiovascular risk factors. Median follow-up time was 2.6 years. Compared with patients with obstructive CAD, the short-term hazard of death (≤30 days) was lower in both patients with non-obstructive CAD [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.27-0.89, P = 0.018] and normal coronary arteries (HR 0.31, 95% CI 0.11-0.83, P = 0.021). In contrast, the long-term hazard of death (>30 days) was similar in patients with non-obstructive CAD (HR 1.15, 95% CI 0.77-1.72, P = 0.487) and higher in patients with normal coronary arteries (HR 2.44, 95% CI 1.58-3.76, P < 0.001), regardless of troponin levels. Causes of death were cardiovascular in 70% of patients with obstructive CAD, 38% with non-obstructive CAD, and 32% with normal coronary arteries. Finally, patients without obstructive CAD had lower survival compared with an age and sex matched general population. Conclusions STE-ACS patients without obstructive CAD had a long-term risk of death similar to or higher than patients with obstructive CAD. Causes of death were less often cardiovascular. This suggests that STE-ACS patients without obstructive CAD warrant medical attention and close follow-up.

Outcome of Alcohol Septal Ablation in Mildly Symptomatic Patients With Hypertrophic Obstructive Cardiomyopathy: A Long‐Term Follow‐Up Study Based on the Euro‐Alcohol Septal Ablation Registry

Background The long‐term efficacy and safety of alcohol septal ablation (ASA) in patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been demonstrated. The aim of this study was to evaluate the long‐term outcomes of mildly symptomatic patients with hypertrophic obstructive cardiomyopathy treated with ASA. Methods and Results We retrospectively evaluated consecutive patients enrolled in the Euro‐ASA registry (1427 patients) and identified 161 patients (53±13 years; 27% women) who were mildly symptomatic (New York Heart Association [NYHA] class II) pre‐ASA. The median (interquartile range) follow‐up was 4.8 (1.7–8.5) years. The clinical outcome was assessed and compared with the age‐ and sex‐matched general population. The 30‐day mortality after ASA was 0.6% and the annual all‐cause mortality rate was 1.7%, which was similar to the age‐ and sex‐matched general population (P=0.62). A total of 141 (88%) patients had resting left ventricular outflow tract gradient at the last clinical checkup ≤30 mm Hg. Obstruction was reduced from 63±32 to 15±19 mm Hg (P<0.01), and the mean NYHA class decreased from 2.0±0 to 1.3±0.1 (P<0.01); 69%, 29%, and 2% of patients were in NYHA class I, II, and III at the last clinical checkup, respectively. Conclusions Mildly symptomatic hypertrophic obstructive cardiomyopathy patients treated with ASA had sustained symptomatic and hemodynamic relief with a low risk of developing severe heart failure. Their survival is comparable to the general population.

Low procedure-related mortality achieved with alcohol septal ablation in European patients

Two thirds of patients with hypertrophic cardiomyopathy (HCM) suffer from a left ventricular obstruction associated with more symptoms and worse prognosis [1] ; [2]. According to American and European Guidelines on HCM, there are two main therapeutic alternatives for treating the left ventricular obstruction: surgical myectomy and alcohol septal ablation (ASA) [1] ; [2]. Both these alternatives are considered safe and effective. However, Panaich et al. have recently demonstrated real world American data from the Nationwide Inpatient Sample (NIS) database showing an almost 6% in-hospital mortality rate associated with surgical myectomy [3]. This study is important because it contradicts lower, previously established post-operative mortality rates, which were estimated to be ~ 1% and were calculated using data from high-volume centers. Importantly, however, current guidelines on HCM have been based only on results of these high-volume centers [1] ; [2]. Along this line, Maron et al. recently found that in five major high-volume HCM centers in North America, the 30-day operative mortality rate was only 0.4% over the past 15 years (n = 3.696, mean age 54 ± 14 years) [4], i.e., one fifteenth of mortality rate reported by Panaich et al. [3]. A recent meta-analysis of long-term outcomes after septal reduction therapy, including 24 studies from tertiary HCM centers around the world, showed that the peri-procedural mortality rate of ASA was 1.3%, compared to 2.5% in patients undergoing myectomy [5]. However, when studies from before the year 2000 were excluded, as Maron et al. suggest [4], these figures became similarly low (1.3% vs. 1.1%, respectively). The same held true for the long-term mortality rates.