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Risk stratification for sudden death (SD) is an essential component of hypertrophic cardiomyopathy (HC) management, given the proven effectiveness of implantable cardioverter-defibrillators (ICD) for preventing SD. Although highly effective in identifying high-risk patients, current stratification algorithms remain incomplete and novel strategies are encouraged. In this regard, reliability of the statistical model to predict SD risk in HC, as recommended by the recent European Society of Cardiology (ESC) guidelines, was retrospectively tested in an independent cohort of 1,629 consecutive patients with HC aged ≥16 years. Of the 1,629 patients, 35 incurred SD events, but only 4 of these (11%) had high predictive risk scores >6%/5 years consistent with an ICD recommendation, and most (60%; n = 21) had scores <4%/5 years that would not justify ICDs. Of 46 high-risk patients with appropriate ICD interventions for ventricular fibrillation/tachycardia, 27 (59%) had low SD risk scores of <4%/5 years, regarded by ESC as insufficient to recommend ICDs, and only 12 (26%) had scores >6%/5 years, considered an ICD indication; 11 of these 12 had already met conventional criteria warranting implantation with 2 to 3 risk markers. Of 414 patients with ICDs but without appropriate interventions, 258 (62%) had low risk scores (<4%/5 years) that would argue against implant. In conclusion, primary risk stratification using the ESC prognostic score applied retrospectively to a large independent HC cohort proved unreliable for prediction of future SD events. Most patients with HC with SD or appropriate ICD interventions were misclassified with low risk scores and therefore would have remained unprotected from arrhythmic SD without ICDs.

Recent data from the National Cardiovascular Data Registry indicate that women with ST-segment-elevation myocardial infarction (STEMI) continue to have higher mortality and reported delays in treatment compared with men. We aimed to determine whether the sex difference in mortality exists when treatment disparities are reduced. Using a prospective regional percutaneous coronary intervention (PCI)–based STEMI system database with a standardized STEMI protocol, we evaluated baseline characteristics, treatment, and clinical outcomes of STEMI patients stratified by sex. From March 2003 to January 2016, 4,918 consecutive STEMI patients presented to the Minneapolis Heart Institute at Abbott Northwestern Hospital regional STEMI system including 1,416 (28.8%) women. Compared with men, women were older (68.4 vs 60.9 years) with higher rates of hypertension (66.7% vs 55.7%), diabetes (21.7% vs 17.4%), and cardiogenic shock (11.5% vs 8.0%) (all P < .001). Pre-revascularization medications and PCI were performed with same frequencies, but women were less likely to receive statin or antiplatelet therapy at discharge. After age adjustment, women had similar in-hospital mortality to men (5.1% vs 4.8%, P = .60) despite slightly longer door-to-balloon time (95 vs 92 minutes, P = .004). Five-year follow-up confirmed absence of a sex disparity in age-adjusted survival post-STEMI. Previously reported treatment disparities between men and women are diminished in a regional PCI-based STEMI system using a standardized STEMI protocol. No sex differences in short-term or long-term age-adjusted mortality are present in this registry despite some treatment disparities. These results suggest that STEMI health care disparities and mortality in women can be improved using STEMI protocols and systems.

We aimed to characterize the clinical and pathologic findings of aortic dissection (AD) over a nearly 60-year period. The Jesse E. Edwards Registry of Cardiovascular Disease database was queried for cardiac specimens from autopsies with AD as a diagnosis and compared 2 cohorts: early (1956-1992) and current (1993-2015). From 1956 to 2015, 338 cases (166 early, 170 current) with AD were included (mean age: 60; 62% male). The AD was 86% type A and 14% type B. Sixty-two percent of cases were under medical care at time of death (61% early, 62% current, P = not significant). Of those under medical care, 63% were not diagnosed prior to death (64% early, 62% current, P = not significant). Risks for dissection did not differ between time intervals and include left ventricular hypertrophy, suggestive of hypertension (84%), prior cardiovascular surgery (38%), bicuspid valve (14%), and connective tissue disease (9%). An intimal tear was identified in the ascending aorta in the majority (68%), followed by descending (14%), root (9.5%), and arch (7%). Aortic rupture occurred in 58%, most frequently in the ascending aorta (41%). In a large cardiovascular registry, >60% of cases of AD were not detected clinically and first identified at autopsy. Although diagnostic techniques have significantly improved over the time interval, the percentage of AD discovered at autopsy did not differ from the early to the current era. The most prevalent risk factors for dissection including hypertension and prior cardiovascular surgery remain similar in both time periods. AD death is related to rupture of the aorta in the majority of cases. [Display omitted]

In hypertrophic cardiomyopathy (HC), atrial fibrillation (AF) is an important determinant of clinical deterioration due to heart failure or embolic stroke. This study characterizes left atrial (LA) structural and functional parameters to establish markers predictive of AF risk, using cardiovascular magnetic resonance (CMR) imaging. We studied 427 consecutive patients with HC in sinus rhythm with CMR (age 44 ± 18 years), including 41 who developed clinically overt AF after study entry (2.6 ± 2.1 years), 49 patients with AF before CMR, 337 patients with HC but without AF, and 244 normal controls. LA chamber was assessed for absolute and indexed end-diastolic volume (LAEDV), end-systolic volume, and percent ejection fraction (LAEF). In the 41 prospectively studied patients with HC who developed AF during follow-up, LAEDV was significantly greater than in patients without AF (146 ± 48 vs 107 ± 37 ml) or in normal controls (81 ± 24 ml, p <0.001). Percent LAEF was lower in patients developing AF (36 ± 10%) than without AF (46 ± 12%) or controls (55 ± 9%, p <0.001). Multivariate analysis identified LAEF (<38%), LAEDV (≥118 ml), and age (≥40 years) as independently associated with AF occurrence. In conclusion, CMR measures of LA remodeling and dysfunction reliably identified patients with HC at risk for future development of AF. Decrease in LAEF represents a strong novel marker of susceptibility to AF in this disease.

Hypertrophic cardiomyopathy (HC) has become a contemporary and treatable genetic heart disease, now with disease-related mortality reduced to as low as 0.5% per year, based largely on more effective risk stratification and the use of the implantable cardioverter-defibrillator for primary prevention of sudden death. This paradigm change in the natural history of HC has caused us to reconsider the overall mortality risk in this disease. We interrogated the databases of 2 HC referral centers, Minneapolis Heart Institute and Tufts Medical Center. Of 1,902 consecutive patients evaluated between 1992 and 2013, 1,653 patients (87%) have survived to the end of follow-up and 249 patients (13%) have died. Most deaths (178 of 249; 72%) were unrelated to HC, commonly because of cancer and predominantly in older patients. Non-HC mortality was significantly more common in adults presenting ≥60 years and least common in the youngest patients aged <30 years (p <0.001). Notably, deaths from non-HC causes substantially exceeded HC-related causes by 2.6-fold (p <0.001). In conclusion, only about 25% of patients with HC ultimately died of their disease, including predominantly those who were <30 years of age. These data allow patients with HC to develop a more realistic and reassured perception of their disease.

Although tako-tsubo cardiomyopathy (TTC) is regarded as a reversible condition with favorable outcome, a malignant clinical course evolves in some subjects. In this single-institution experience, we describe the clinical profile of patients with adverse TTC outcome. A cohort of 249 consecutive patients with TTC was interrogated for those with acute unstable presentation during the first 24 hours. Forty-seven patients (19%) experienced early complicated clinical course with cardiac arrest in 9 (ventricular fibrillation, n = 4, pulseless electrical activity, n = 3, and asystole, n = 2) or marked hypotension in 38 (systolic blood pressure ≤90 mm Hg requiring vasopressors and/or balloon pump). Of the 47 patients, Killip class III to IV heart failure was present in 30 (64%). Despite treatment, 8 patients (3%; all women) died inhospital due to respiratory failure, cardiogenic shock, or anoxic brain injury. All 8 inhospital deaths occurred among the 47 patients with unstable presentation, including 2 after cardiac arrest and 6 with marked hypotension. Post-TTC event mortality for a period of 4.7 ± 3.4 years significantly exceeded that in a matched general US population (standardized mortality ratio 1.4; 95% confidence interval 1.1 to 1.9; p = 0.005) largely due to noncardiac co-morbidities. In conclusion, contrary to widespread perception, TTC is not an entirely benign and reversible condition. Among this large cohort, a high-risk subgroup was identified with cardiac arrest or hemodynamic instability, accounting for all hospital deaths. Hospital nonsurvivors had a variety of irreversible co-morbid conditions with the potential to compromise clinical status and adversely affect short-term survival. Long-term survival after hospital discharge was also reduced compared with the general population because of noncardiac co-morbidities.

Patients with refractory angina who are suboptimal candidates for further revascularization have improved exercise time, decreased angina frequency, and reduced major adverse cardiac events with intramyocardial delivery of CD34+ cells. However, the effect of CD34+ cell therapy on health care expenditures before and after treatment is unknown. We determined the effect of CD34+ cell therapy on cardiac‐related hospital visits and costs during the 12 months following stem cell injection compared with the 12 months prior to injection. Cardiac‐related hospital admissions and procedures were retrospectively tabulated for patients enrolled at one site in one of three double‐blinded, placebo‐controlled CD34+ trials in the 12 months before and after intramyocardial injections of CD34+ cells vs placebo. Fifty‐six patients were randomized to CD34+ cell therapy (n = 37) vs placebo (n = 19). Patients randomized to cell therapy experienced 1.57 ± 1.39 cardiac‐related hospital visits 12 months before injection, compared with 0.78 ± 1.90 hospital visits 12 months after injection, which was associated with a 62% cost reduction translating to an average savings of $5500 per cell therapy patient. Patients in the placebo group also demonstrated a reduction in cardiac‐related hospital events and costs, although to a lesser degree than the CD34+ group. Through 1 January 2019, 24% of CD34+ subjects died at an average of 6.5 ± 2.4 years after enrollment, whereas 47% of placebo patients died at an average of 3.7 ± 1.9 years after enrollment. In conclusion, CD34+ cell therapy for subjects with refractory angina is associated with improved mortality and a reduction in hospital visits and expenditures for cardiac procedures in the year following treatment. The total cardiovascular hospitalizations, procedures and emergency room visits are significantly reduced in patients with refractory angina in the 12 months following intramyocardial CD34+ progenitor cell injections compared to the 12 months prior to injections (P = .002).

Refractory progressive heart failure (HF) is becoming the predominant cause of mortality in nonobstructive hypertrophic cardiomyopathy (HC). To anticipate development of this important and often unpredictable clinical course, we investigated whether left ventricular diastolic dysfunction, assessed by echocardiographic Doppler parameters, could identify a subset of patients with HC without obstruction at rest who would experience progression of HF. Diastolic function parameters, assessed by Doppler tissue imaging (DTI), mitral inflow, and pulmonary venous flow were measured in 274 consecutive adult patients with HC evaluated from 2003 to 2007. DTI and other diastolic and clinical/demographic parameters were measured against the composite end point of HF/death, heart transplantation, or progression to advanced New York Heart Association functional class III/IV symptoms and sudden death (SD)/implantable defibrillator (ICD) interventions. HF end points were reached in 19 of 274 patients (7%) over a follow-up period of 4.0 ± 2.3 years. Variables significantly associated with HF outcome by univariate analysis included male gender, initial New York Heart Association class II, lower ejection fraction, and reduced septal and lateral e′ mitral annular tissue velocities. Multivariable analysis showed only a reduced lateral e′ mitral annular tissue velocity to be independently associated with the composite HF end points (HR 0.77; 95% CI 0.65 to 0.91; p = 0.003). In addition, estimated pulmonary arterial systolic pressure and extensive late gadolinium enhancement by magnetic resonance were also associated with HF outcome (p = 0.04 and p <0.001, respectively). No Doppler (or clinical) variable was associated with SD/appropriate ICD interventions. In conclusion, in HC without outflow obstruction at rest, diastolic dysfunction, evidenced by DTI-reduced lateral e′ mitral annular tissue velocity, was associated with adverse long-term HF outcome but was unrelated to SD. This echocardiographic marker provides a potential noninvasive strategy for anticipating progressive HF in this HC patient group.

Tako-tsubo cardiomyopathy (TTC) is an acute reversible cardiac condition usually triggered by stressful events, with a predilection for older women and clinical presentation often confused with acute coronary syndrome. Definition of the diurnal hourly pattern of TTC events may contribute to understanding the pathogenesis of this complex entity. We prospectively enrolled 186 consecutive patients with TTC (68 ± 14 years old, 95% women) and, for comparison, 2,975 patients with ST-segment elevation myocardial infarction (STEMI) at the Minneapolis Heart Institute over the same period. Circadian periodicity was analyzed for hourly occurrence of events throughout the day and for days of the week and months of the year. Occurrence of TTC showed a nonuniform distribution with a distinctive afternoon peak from 12:00 (noon) to 4:00 p.m., comprising 28% (n = 52) of all events, and with the nadir at 12 to 4 a.m. (chi-square 25.6, p <0.001). Patients with events within the peak were older (73 ± 13 years) than other patients (66 ± 13 years, p = 0.0025). Events were uniformly distributed over days of the week and months (p = 0.2 and 0.47, respectively). In contrast, patients with STEMI showed peak occurrence in the early morning hours, 8:00 a.m. to 12:00 p.m., comprising 24% of all events (chi-square 248, p <0.001). In conclusion, TTC events occurred in a circadian pattern with a peak in the afternoon hours, distinctive from the predilection of STEMI for morning hours. This timing of TTC events is most consistent with mechanisms underlying stressful life situations that usually trigger this condition.

Multiple medications have proven efficacy for the primary prevention of coronary heart disease (CHD), but the appropriate patient population remains controversial. Even in the presence of multiple cardiovascular risk factors, many patients are not considered high risk and are not offered preventive medications despite proven efficacy. We analyzed a prospective cohort of 1,710 consecutive ST-elevation myocardial infarction (STEMI) patients treated in a regional STEMI system from May 2007 to July 2010 and enrolled in a comprehensive database that includes preadmission medications. Of the 1,707 patients analyzed, 1,180 (69.1%) did not have known CHD before their event; and 482 (41.7%) of those patients had premature events (men <55 years old, women <65 years old). In patients without known CHD, cardiovascular risk factors were abundant (52.1% had hypertension, 43.6% had dyslipidemia, 41.4% had a family history of CHD, 58.5% were current or former smokers, and 14.9% were diabetic). Despite the high prevalence of risk factors, only 24.1% were on aspirin, 16.1% were on a statin, and only 7.8% were taking an aspirin and statin. Use of preventive medications was even less common in patients with premature events, including aspirin (15.2% vs 30.2%, P value < .001), statins (11.1% vs 19.5%, P value < .001), and the combination (5.6% vs 9.4%, P value < .001). Approximately 70% of a contemporary STEMI population did not have known CHD before their event, and >40% of those events would be considered premature. Despite the significant burden of cardiovascular risk factors, use of preventive therapy was alarmingly low in patients presenting with STEMI.