Abstract Background In obstructive hypertrophic cardiomyopathy (HCM), the primary goal of therapy is to improve patient quality of life by decreasing symptom burden. Increasingly, cardiopulmonary exercise testing (CPET), with peak oxygen consumption (pVO2) and ventilator efficacy (VE/VCO2), is used to assess efficacy of novel therapies in clinical studies and selectively in clinical practice to determine treatments. However, the relationship of CPET variables to symptom burden in HCM is not well established. Therefore, we examined the relationship between CPET variables and health status measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional classification in a cohort of obstructive HCM patients. Methods Consecutive patients with HCM and resting left ventricular outflow tract (LVOT) obstruction (≥50 mmHg) underwent CPET between October 2022 to January 2024. Patients with a peak RER <1.0 were excluded (n=4). To investigate distribution of patient reported health status (KCCQ) and NYHA functional classification, patients were stratified into groups for pVO2 (<14, 14-20, and >20 mL/kg/min) to reflect moderate to severe, mild to moderate, and little to no functional limitation, respectively. Results Of 58 patients, clinical evaluation was at 59 ± 13 years of age, 55% male, with LVOT gradient of 83 ± 28 mmHg at rest with 84% NYHA class II or III and 76% with KCCQ overall summary (OS) <75. Both pVO2 and VE/VCO2 had significant but weak correlation with NYHA class and KCCQ scores (Table 1), with the strongest correlation observed with pVO2 and KCCQ-OS (R2= 0.13, p=0.004). In contrast, % predicted pVO2 was not significantly correlated with NYHA or KCCQ. Notably, despite 14 patients being classified as having little to no limitations by pVO2, 29% of these patients had mild to moderate disability and 29% had moderate to severe disability by KCCQ-OS (Figure 1). Conclusion In patients with symptomatic obstructive HCM, objective measures of exercise performance, including pVO2 and VE/VCO2, correlate poorly with measurements of health status. These data suggest that CPET results should not be considered a surrogate marker of heart failure symptom burden in obstructive HCM.

Abstract Background Hypertrophic cardiomyopathy (HCM) patients with a pathogenic variant are presumed to have worse prognosis than patients without a pathogenic mutation. However, the genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and relationship between genotype status and outcomes have not been completely resolved. Objective We assessed a large international HCM cohort to define the natural history and clinical consequences of genotype status. Methods Consecutive patients (n=1468) with established clinical HCM diagnosis underwent genetic testing focused on HCM-related genes. Patients with pathogenic or likely pathogenic variants were considered genotype positive (G+), and those without definite disease-causing mutation or a variant of uncertain significance (VUS) were considered genotype negative (G-). Patients were followed for 9.6 ± 8.2 years for clinical outcomes. Results Of 1468 HCM patients, 1156 (79%) were G - and 312 (21%) were G+. Over the follow-up 116 (10%) G- patients died at 70 ± 14 years, including in 26 (2.2%) from HCM-related causes. HCM-related mortality was not significantly different in G- patients (0.3%/year) as compared to G+ patients (0.3%/year) when adjusted for age (HR 0.93, 95% CI 0.38-2.30, p=0.87). All-cause mortality was not different among these groups (0.7%/year G- vs. 0.6%/year G+) when adjusted for age (HR 0.62, 95% CI 0.3-1.2, p=0.14) or comorbidities (HR 0.78, 95% CI 0.46-1.31, p=0.35). Rate of progression to advanced heart failure NYHA class III/IV in nonobstructive patients was not different in G- (4%/ year) vs. G+ (3%/year, HR 1.20, 95% CI 0.63-2.26, p=0.58). Sudden death events (appropriate ICD shocks, aborted cardiac arrest and sudden death) were more frequent in G+ patients (1.7%/year) than in G- patients (0.5%/year), albeit of borderline statistical significance when adjusted for age and SD risk factors (HR 1.58, 95% CI 1.00-2.49, p=0.05). Conclusions In this large consecutive genotyped cohort, all-cause and HCM-related mortality was unrelated to genotype status. Substantial proportion of G- patients experienced progressive HF, at a similar rate when compared to G+ patients. Although G- patients had less frequently SD events, genotype negative status could not be considered benign.FiguresTable

What is the problem and what is known about it so far? Triathlon is a competitive sporting event that began in the 1970s. It combines swimming, bicycling, and running and has become popular among adult recreational athletes. Some people have questioned the safety of triathlons, especially as they grow in popularity and attract increasing numbers of recreational athletes who may have underlying, undiagnosed medical conditions or may not train adequately for the swimming part of the event. Why did the researchers do this particular study? To describe death and cardiac arrest among triathlon participants. Who was studied? Participants in U.S. triathlons from 1985 to 2016. How was the study done? The researchers gathered information on deaths and cardiac arrests in U.S. triathlon participants from 1985 to 2016 from various sources, including the U.S. National Registry of Sudden Death in Athletes and USA Triathlon (USAT) records. From these sources, they collected data on the characteristics of participants who died or had a cardiac arrest, the timing of the death or cardiac arrest during the race, and such factors as the air and water temperature during the race. To help estimate the proportion of participants who died or had a cardiac arrest, the researchers collected information about the number of participants who completed triathlons from USAT records of participants who completed races from 2006 to 2016. This information was not available for earlier years. What did the researchers find? A total of 107 sudden deaths, 13 cardiac arrests that responded to resuscitation, and 15 trauma-related deaths occurred in triathlon participants from 1985 to 2016. Of the participants who died, 85% were men and their average age was 47 years. Most sudden deaths and cardiac arrests occurred during the swimming event (90), but also happened during bicycling (7) and running (15). All trauma-related deaths occurred during bicycling. Using the data from 2006 to 2016, the researchers estimated that death or cardiac arrest occurs in about 1.74 of 100000 triathlon participants (2.4 per 100000 men and 0.74 per 100000 women). The risk was 18.6 per 100000 in men older than 60 years. The risk for death or cardiac arrest was similar in long, intermediate, and short triathlons. Autopsy information was available for 61 of the triathletes who died, 27 of whom had evidence of heart system abnormalities. What were the limitations of the study? Identification of deaths and cardiac arrests may be incomplete in the registry data used for this study, so the researchers may have underestimated the number of events. Also, medical history and autopsy information were not available for most of the included deaths. What are the implications of the study? Sudden death, cardiac arrest, and trauma-related death occur during triathlons but are infrequent. Most of the deaths occurred in middle-aged and older men during the swimming part of the race.

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with diverse phenotypic and genetic expression, clinical presentation, and natural history. HCM has been recognized for 55 years, but recently substantial advances in diagnosis and treatment options have evolved, as well as increased recognition of the disease in clinical practice. Nevertheless, most genetically and clinically affected individuals probably remain undiagnosed, largely free from disease-related complications, although HCM may progress along 1 or more of its major disease pathways (i.e., arrhythmic sudden death risk; progressive heart failure [HF] due to dynamic left ventricular [LV] outflow obstruction or due to systolic dysfunction in the absence of obstruction; or atrial fibrillation with risk of stroke). Effective treatments are available for each adverse HCM complication, including implantable cardioverter-defibrillators (ICDs) for sudden death prevention, heart transplantation for end-stage failure, surgical myectomy (or selectively, alcohol septal ablation) to alleviate HF symptoms by abolishing outflow obstruction, and catheter-based procedures to control atrial fibrillation. These and other strategies have now resulted in a low disease-related mortality rate of <1%/year. Therefore, HCM has emerged from an era of misunderstanding, stigma, and pessimism, experiencing vast changes in its clinical profile, and acquiring an effective and diverse management armamentarium. These advances have changed its natural history, with prevention of sudden death and reversal of HF, thereby restoring quality of life with extended (if not normal) longevity for most patients, and transforming HCM into a contemporary treatable cardiovascular disease. (C) 2014 by the American College of Cardiology Foundation.

Sudden death (SD) in athletes represents a cardiac ‘earthquake’ affecting apparently healthy and highly trained individuals. This is not due to excessive demands on a normal heart, as occurred to Phidippides in Marathon, because our body has built-in safeguard mechanisms—dyspnea, angina, fatigue—to protect us from physical exhaustion. Autopsy investigations reveal that SD in athletes occurs three times more often than in non-athletes, and is caused by concealed cardiovascular abnormalities, mostly structural, that are unmasked by activity-triggered electrical instability.1–5 The structural culprits may be any of the cardiovascular components, including aorta, coronary arteries, myocardium, valves, conduction system and ion channels.1 The ECG is often abnormal, and its implementation in Italy for obligatory preparticipation screening has resulted in progressive reductions by 90% of SD in athletes aged 12–35 years between 1979 and 20024 (figure 1). This was mostly attributable to identification and disqualification of people affected by cardiomyopathies. Figure 1 Annual incidence rates of sudden death (SD) per 100 000 person, among screened competitive athletes and unscreened non-athletes 12–35 years of age in the Veneto Region of Italy, from 1979 to 2002. During the study period (the nationwide preparticipation screening program was initiated in 1982), the annual incidence of SD declined by 89% in screened athletes (p for trend <0.001). In contrast, the incidence of SD did not demonstrate consistent changes over that time in unscreened non-athletes. Arrhythmogenic right ventricular cardiomyopathy—unknown until the 1980s—is the major cause of SD in Italian athletes (relative risk 5.4 compared with non-athletes), and can now be identified at preparticipation screening by application of specific diagnostic criteria. Hypertrophic cardiomyopathy, on the other hand, was a rare cause of athlete SD in Italy compared with the US.4 ,6 In fact, abnormalities of the screening 12-lead ECG prompted echocardiography, which was diagnostic in …

Classifications of heart muscle diseases have proved to be exceedingly complex and in many respects contradictory. Indeed, the precise language used to describe these diseases is profoundly important. A new contemporary and rigorous classification of cardiomyopathies (with definitions) is proposed here. This reference document affords an important framework and measure of clarity to this heterogeneous group of diseases. Of particular note, the present classification scheme recognizes the rapid evolution of molecular genetics in cardiology, as well as the introduction of several recently described diseases, and is unique in that it incorporates ion channelopathies as a primary cardiomyopathy.

As hypertrophic cardiomyopathy is a common cause of sudden deaths among athletes, differentiating this condition from the non-pathological "athlete's heart" presents an important challenge.

BACKGROUND:The implanted cardioverter-defibrillator (ICD) has been shown to improve survival in adult patients with high risk acquired cardiac disease, with a cost-effectiveness ratio in the range of $30,000 to $185,000 per quality-adjusted-life-year saved. However, data on the benefit and cost-effectiveness of device therapy in high-risk patients with inherited cardiac disorders are limited.METHODS:We developed two separate computer-based analytical models to compare non-ICD with ICD therapy in patients (age range: 10-75 years) with long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM). In each disease entity patients were stratified into low-risk (no known risk factors); high-risk (known risk factors [primary prevention]); and very high-risk (prior near-fatal events [secondary prevention]). Net costs were defined as the difference between costs resulting from treatment of the disease and savings due to gained productivity attributable to prevention of sudden cardiac death. Outcome was defined as costs per quality-adjusted life-years saved.RESULTS:In LQTS, defibrillator therapy was shown to be cost effective in high-risk male patients (incremental cost-effectiveness ratio [ICER]=$3328 per quality-adjusted-life-year saved), and cost saving in high-risk females (ICER=$7102 gained per quality-adjusted-life-year saved) and very high-risk males and females (ICER=$15,483 and 19,393 gained per quality-adjusted-life-year saved, respectively). In HCM, defibrillator therapy was cost saving in both male and female high-risk (ICER=$17,892 and $17,526 gained per quality-adjusted-life-year saved, respectively) and very high-risk (ICER $22,944 and $22,329 gained per quality-adjusted-life-year saved, respectively) patients. Defibrillator therapy was not shown to be cost effective in low-risk patients with either LQTS or HCM (ICER in the range of $400,000 to $600,000 lost per quality-adjusted-life-year saved). Sensitivity analyses were consistent with the results in each risk group.CONCLUSIONS:In appropriately selected patients with inherited cardiac disorders, early intervention with ICD therapy is cost-effective to cost saving due to added years of gained productivity when the lifespan of an individual at risk is considered.

HomeCirculationVol. 112, No. 3Letter Regarding Article by Sharkey et al, "Acute and Reversible Cardiomyopathy Provoked by Stress in Women From the United States" Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter Regarding Article by Sharkey et al, "Acute and Reversible Cardiomyopathy Provoked by Stress in Women From the United States" Hassan Abdel-Aty, Rainer Dietz and Jeanette Schulz-Menger Hassan Abdel-AtyHassan Abdel-Aty Franz-Volhard-Klinik, Kardiologie, Universitätmedizin Berlin, Berlin, Germany , Rainer DietzRainer Dietz Franz-Volhard-Klinik, Kardiologie, Universitätmedizin Berlin, Berlin, Germany and Jeanette Schulz-MengerJeanette Schulz-Menger Franz-Volhard-Klinik, Kardiologie, Universitätmedizin Berlin, Berlin, Germany Originally published19 Jul 2005https://doi.org/10.1161/CIRCULATIONAHA.105.544114Circulation. 2005;112:e51To the Editor:We read with interest the article by Sharkey et al1 describing the clinical and cardiovascular magnetic resonance (CMR) features of the apical ballooning cardiomyopathy. We have a few concerns about the interpretation of the CMR findings in the article as well as in the related editorial.2The authors suggest that the lack of mid-wall delayed enhancement in their series should exclude myocardial inflammation as a possible underlying mechanism explaining their findings. We have recently investigated the diagnostic performance of various CMR techniques to identify acute myocarditis3 and found that delayed enhancement occurs in only 44% of these patients, whereas T2-weighted abnormalities reflecting myocardial edema and early global enhancement are noted in >80% of the cases. For this reason, we believe that the CMR approach of the authors does not allow exclusion of myocardial inflammation in those cases with certainty.The related editorial suggested that the lack of delayed enhancement excludes the presence of myocardial edema in these patients. We have shown in the same report3 that global or focal myocardial edema is frequently observed in the absence of delayed enhancement. We have also previously shown that chronic myocardial scars exhibit delayed enhancement without myocardial edema.4 Furthermore, we recently investigated a female patient with "taku-tsubo" cardiomyopathy and found overt regional high T2 signal intensity without any evidence of delayed enhancement. Accordingly, we believe that no firm conclusion could be drawn about the presence or absence of myocardial edema in these patients in the absence of T2-weighted imaging experiments.The editorial also suggested that "gadolinium-enhanced MRI … failed to detect regional T2 enhancement which has been shown to detect myocardial inflammation and necrosis." We have 2 concerns about this statement: First, the enhancement effect of gadolinium is mainly caused by its effect on T1 relaxation time. Second, the article cited to support the statement5 did not include any T2-weighted imaging experiments.Despite these concerns, we congratulate the authors on their report, which provides many new insights into this rare and yet clinically relevant and novel cardiomyopathy. References 1 Sharkey SW, Lesser JR, Zenovich AG, Maron MS, Lindberg J, Longe TF, Maron BJ. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation. 2005; 111: 472–479.LinkGoogle Scholar2 Dec GW. Recognition of the apical ballooning syndrome in the United States. Circulation. 2005; 111: 388–390.LinkGoogle Scholar3 Abdel-Aty H, Boyé P, Zagrosek A, Wassmuth R, Kumar A, Messroghli D, Bock P, Dietz R, Friedrich MG, Schulz-Menger J. Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches. J Am Coll Cardiol. 2005; 45: 1815–1822.CrossrefMedlineGoogle Scholar4 Abdel-Aty H, Zagrosek A, Schulz-Menger J, Taylor AJ, Messroghli D, Kumar A, Gross M, Dietz R, Friedrich MG. Delayed enhancement and T2-weighted cardiovascular magnetic resonance imaging differentiate acute from chronic myocardial infarction. Circulation. 2004; 109: 2411–2416.LinkGoogle Scholar5 Mahrholdt H, Goedecke C, Wagner A, Meinhardt G, Athanasiadis A, Vogelsberg H, Fritz P, Klingel K, Kandolf R, Sechtem U. Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology. Circulation. 2004; 109: 1250–1258.LinkGoogle ScholarcirculationahaCirculationCirculationCirculation0009-73221524-4539Lippincott Williams & WilkinsResponseSharkey Scott W., , Lesser John R., , Zenovich Andrey G., , Longe Terrence F., , Maron Barry J., , and Maron Martin S., 19072005We appreciate the interest of Dr Abdel-Aty and colleagues in our work.1 These investigators raise the question of whether the absence of postgadolinium-delayed hyperenhancement with T1-weighted cardiac MRI (CMR) reported in our patients with stress ("tako-tsubo") cardiomyopathy failed to exclude myocardial inflammation because T2-weighted imaging data were not presented.1For several reasons, we believe that is a highly unlikely scenario for myocarditis to be the undetected and underlying mechanism responsible for stress cardiomyopathy in such a sizeable patient cohort. T1-weighted imaging is the preferred and established technique to assess myocardial viability and exclude infarction and necrosis,2 which was in fact the priority in this particular study. Indeed, 21 of our 22 study patients showed myocardial viability without evidence of delayed hyperenhancement (the other patient had an apical infarct caused by a previous cardiac arrest).In our group of severely symptomatic patients with stress cardiomyopathy, we did initially perform some T2-weighted scans (in addition to T1-weighted imaging), which are preferable for the interrogation of myocardial edema (consistent with myocarditis). Of the 22 patients, 9 had technically adequate T2-weighted images, and 2 of these (22%) had T2-weighted scans consistent with myocardial edema. We found no difference, however, in clinical profile (including premonitory vital infection and laboratory evidence of systemic inflammation) between the 2 patients with myocardial edema and the 7 patients without this finding; furthermore, 1 of the 2 patients with myocardial edema had a myocardial biopsy that was negative for myocardial inflammation. Finally, and perhaps most importantly, myocarditis is not particularly consistent with the clinical profile evident in each of our patients with stress cardiomyopathy (ie, rapidly reversible apical ballooning with hypercontractile base involving all 3 vascular territories). Therefore, although we appreciate the reasonable insights of Abdel-Aty et al, we do not believe there are any data to substantiate an important role for myocarditis in our patients with stress cardiomyopathy.**Original coauthor Dr Jana Lindberg did not participate in the drafting of this letter. eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Siedlecka U, Arora M, Kolettis T, Soppa G, Lee J, Stagg M, Harding S, Yacoub M and Terracciano C (2008) Effects of clenbuterol on contractility and Ca 2+ homeostasis of isolated rat ventricular myocytes , American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00258.2008, 295:5, (H1917-H1926), Online publication date: 1-Nov-2008. Lynch G and Ryall J (2008) Role of β-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease, Physiological Reviews, 10.1152/physrev.00028.2007, 88:2, (729-767), Online publication date: 1-Apr-2008. Guyette F, Greenwood M, Neubecker D, Roth R and Wang H (2009) Alternate Airways in the Prehospital Setting (Resource Document to NAEMSP Position Statement), Prehospital Emergency Care, 10.1080/10903120601021150, 11:1, (56-61), Online publication date: 1-Jan-2007. Williams J and Conte J (2006) Ventricular Assist Devices Treatment of Advanced Heart Disease, 10.3109/9781420020168.024, (433-458), Online publication date: 1-Mar-2006. Ohuchi K and Takatani S (2014) Currently available ventricular-assist devices: capabilities, limitations and future perspectives, Expert Review of Medical Devices, 10.1586/17434440.3.2.195, 3:2, (195-205), Online publication date: 1-Mar-2006. Dawn B and Bolli R (2005) Cardiac Progenitor Cells, Circulation Research, 97:11, (1080-1082), Online publication date: 25-Nov-2005. July 19, 2005Vol 112, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.105.544114PMID: 16027265 Originally publishedJuly 19, 2005 PDF download Advertisement SubjectsComputerized Tomography (CT)Heart Failure